gen 16-11-18 pgs.1-16 - generics bulletin · 2018. 12. 12. · gen 16-11-18 pgs.1-16.indd 4...

16
16 November 2018 Hikma to reduce global footprint H ikma intends to reduce its geographic footprint from its current presence in around 50 countries worldwide, especially by focusing resources on only the most promising markets in the Middle East and North Africa (MENA) region, under a corporate strategy presented by Siggi Olafsson, who became chief executive officer around nine months ago. Olafsson also wants to treble the group’s return on research and development investment within the next five years. Stressing Hikma’s differentiating factor of being “the only global local player” in the MENA region, Olafsson said the firm was “de-emphasising the number of countries we operate in”. “I would be OK to be in a little bit fewer countries, but be able to grow faster in those markets,” he stated. To that end, the group has identified Algeria, Egypt and Saudi Arabia as ‘Tier 1’ priority MENA markets in which it already has a significant presence, while it will put “minimal investment” and potentially outsource to agents and other third parties in countries such as Morocco, Libya, Tunisia and Sudan. While Olafsson intends to maintain research and development spending at its current level of 6-7% of group turnover, he wants the sales contribution from new launches to roughly treble from 3% in 2017 and about 10% within five years. To do this, Hikma will, he says, both increase its total number of “shots on goal” and target more complex products. Developing Hikma’s pipeline and leveraging partnerships and acquisitions, in part to add products and technologies, form two of three central strategic pillars, alongside driving efficiencies and cutting costs. G Coherus matches Mylan on pegfilgrastim price C RKerXs %iR6ciences ZiOO PDWcK WKe 86 OisWSrice GiscRXnW RIIereG E\ 0\ODn IRr EiRsiPiODr SeJIiOJrDsWiP YersXs WKe reIerence ErDnG ZKen iW EeJins sKiSSinJ WKe IirP¶s 8Gen\cD SeJIiOJrDsWiPcETY Rn -DnXDr\ /iNe %iRcRn¶s )XOSKiOD SeJIiOJrDsWiPMPGE WKDW SDrWner 0\ODn ODXncKeG eDrOier WKis \eDr 8Gen\cD ZiOO Ee SriceG DW 86 Ser Sre IiOOeG s\rinJe D GiscRXnW WR 1eXODsWD¶s ZKROesDOe DcTXisiWiRn cRsW :$& ³%e\RnG OisW Srice Ze DOsR KDYe cRnWrDcWinJ SODns WKDW Ze EeOieYe ZiOO GeOiYer DGGiWiRnDO YDOXe WR SD\ers SrRYiGers DnG SDWienWs in WKe ORnJ WerP IDciOiWDWinJ XSWDNe´ &RKerXs reYeDOeG Speaking during the company’s third-quarter earnings call, Coherus’ management indicated strongly that the company was, for now, prioritising pegfilgrastim efforts in the US over the European Union (EU). This is despite Coherus being among the first companies to obtain a pan-European marketing authorisation approval from the European Commission, and the first to obtain approval from both the US Food and Drug Administration (FDA) and EU regulator. “We haven’t had too much to say about partnering in Europe, for the time being,” company head Denny Lanfear said. “We have been approached by some parties in Europe we continue to chat with some folks. But I think that the company’s best focus is in the US market.” With a freshly-hired US team of more than 70 sales representatives and other commercial personnel behind it in preparation for Udenyca’s launch, Coherus has revealed ambitions to target the entire US Neulasta market, including the originator’s Onpro Kit on-body injector. Senior vice-president of sales Chris Thompson said that the company believed, “through our economic value proposition, as well as the services that we’re going to provide to patients,” Coherus’ pre- filled syringe product would be able to compete with the Neulasta Onpro Kit device. Coherus was also confident in its ability to supply the market, the company said, “and we are prepared to meet our highest expected demand for an extended period of time.” As a mark of quality, Coherus revealed that it had recently received and successfully completed two FDA inspections at Udenyca’s production and testing sites. G COMPANY NEWS 3 Perrigo’s new leader backs generics plans 3 Lannett will axe 250 under 3 savings scheme PPIs place pressure on 4 Chemiphar sales ANI eyes more deals 4 to follow WellSpring Akorn site hit with 11 observations 5 by FDA Richter drops despite rise in Bemfola sales 5 Endo eyes the future and shuns shortages 6 Hikma makes a move for 7 Vietnam’s Medlac Amneal sees uptake dynamics changing 7 US and India drive up profits 8 for Wockhardt Mallinckrodt might divide up Generics 9 Chinese disruption is 9 opportunity for Aceto MARKET NEWS 10 Australia and Canada allow 10 API recognition US midterm elections to have 11 major impact UK’s Supreme Court to rule 11 on obviousness PRODUCT NEWS 12 Pfenex sees date slide for 13 its US teriparatide Momenta settles with Abbvie 13 over Humira Sandoz is rocked by Dutch ‘status quo’ 14 German funds select 15 Imraldi due to price Hikma and Vectura ally on 15 Ellipta rivals REGULARS Events – Conferences and meetings 6 Price Watch UK – Our regular listing 12 People – Kaczmarek will lead 16 G&W Dermatology Issue No.376

Upload: others

Post on 03-Feb-2021

2 views

Category:

Documents


0 download

TRANSCRIPT

  • 16 November 2018

    Hikma to reduce global footprintHikma intends to reduce its geographic footprint from its current presence in around 50countries worldwide, especially by focusing resources on only the most promising markets inthe Middle East and NorthAfrica (MENA) region, under a corporate strategy presented by SiggiOlafsson, who became chief executive officer around nine months ago. Olafsson also wants totreble the group’s return on research and development investment within the next five years.

    Stressing Hikma’s differentiating factor of being “the only global local player” in theMENA region, Olafsson said the firm was “de-emphasising the number of countries we operatein”. “I would be OK to be in a little bit fewer countries, but be able to grow faster in thosemarkets,” he stated. To that end, the group has identified Algeria, Egypt and Saudi Arabia as‘Tier 1’ priority MENAmarkets in which it already has a significant presence, while it will put“minimal investment” and potentially outsource to agents and other third parties in countriessuch as Morocco, Libya, Tunisia and Sudan.

    While Olafsson intends to maintain research and development spending at its current level of6-7% of group turnover, he wants the sales contribution from new launches to roughly treble from3% in 2017 and about 10% within five years. To do this, Hikma will, he says, both increase itstotal number of “shots on goal” and target more complex products. Developing Hikma’s pipelineand leveraging partnerships and acquisitions, in part to add products and technologies, form twoof three central strategic pillars, alongside driving efficiencies and cutting costs. G

    Coherus matches Mylanon pegfilgrastim priceC er s i ciences i c e is rice isc n ere n r i si i re i r s i ers s e re erence r n en i e ins s i in e ir s en ce i r s i c n n r i e i c n s i e i r s ir ner n nc e e r ier is e r en c i e rice er re

    i e s rin e isc n e s s es e c isi i n c s e n isrice e s e c n r c in ns e e ie e i e i er i i n e ersr i ers n ien s in e n er ci i in e er s re e e

    Speaking during the company’s third-quarter earnings call, Coherus’management indicatedstrongly that the company was, for now, prioritising pegfilgrastim efforts in the US over theEuropean Union (EU). This is despite Coherus being among the first companies to obtain apan-European marketing authorisation approval from the European Commission, and the firstto obtain approval from both the US Food and Drug Administration (FDA) and EU regulator.

    “We haven’t had too much to say about partnering in Europe, for the time being,” companyhead Denny Lanfear said. “We have been approached by some parties in Europe we continueto chat with some folks. But I think that the company’s best focus is in the US market.”

    With a freshly-hired US team of more than 70 sales representatives and other commercialpersonnel behind it in preparation for Udenyca’s launch, Coherus has revealed ambitions to targetthe entire US Neulasta market, including the originator’s Onpro Kit on-body injector. Seniorvice-president of sales Chris Thompson said that the company believed, “through our economicvalue proposition, as well as the services that we’re going to provide to patients,” Coherus’ pre-filled syringe product would be able to compete with the Neulasta Onpro Kit device.

    Coherus was also confident in its ability to supply the market, the company said, “and weare prepared to meet our highest expected demand for an extended period of time.” As a markof quality, Coherus revealed that it had recently received and successfully completed two FDAinspections at Udenyca’s production and testing sites. G

    COMPANY NEWS 3Perrigo’s new leader backs generics plans 3

    Lannett will axe 250 under 3savings scheme

    PPIs place pressure on 4Chemiphar sales

    ANI eyes more deals 4to follow WellSpring

    Akorn site hit with 11 observations 5by FDA

    Richter drops despite rise in Bemfola sales 5

    Endo eyes the future and shuns shortages 6

    Hikma makes a move for 7Vietnam’s Medlac

    Amneal sees uptake dynamics changing 7

    US and India drive up profits 8for Wockhardt

    Mallinckrodt might divide up Generics 9

    Chinese disruption is 9opportunity for Aceto

    MARKET NEWS 10Australia and Canada allow 10API recognition

    US midterm elections to have 11major impact

    UK’s Supreme Court to rule 11on obviousness

    PRODUCT NEWS 12Pfenex sees date slide for 13its US teriparatide

    Momenta settles with Abbvie 13over Humira

    Sandoz is rocked by Dutch ‘status quo’ 14

    German funds select 15Imraldi due to price

    Hikma and Vectura ally on 15Ellipta rivals

    REGULARSEvents – Conferences and meetings 6Price Watch UK – Our regular listing 12People – Kaczmarek will lead 16G&W Dermatology

    Issue No.376

    Gen 16-11-18 Pgs.1-16.indd 1 14/11/2018 16:49

  • Gen 16-11-18 Pgs.1-16.indd 2 14/11/2018 16:49

  • 3bulletin16 November 2018

    COMPANY NEWS

    BUSINESS STRATEGY/THIRD-QUARTER RESULTS

    Perrigo’s new leaderbacks generics plansPerrigo’s newly-appointed president and chief executive officer,Murray Kessler, has backed the planned ‘separation’of the firm’s ‘Rx’Prescription US generics operation, but has also praised the business’potential, albeit in the face of a disappointing financial third quarter.

    “I agree with the board’s decision to sell or spin Rx, as it is adistraction to our core Consumer businesses, even though it is a goodand profitable business in its own right,” Kessler told investors duringhis first Perrigo earnings call after joining the company on 8 October.

    But, Kessler insisted, “unlike the Consumer business, the pipelineon Rx is robust, and we are we are just a few US Food and DrugAdministration (FDA) approvals away from significantly changing thetrajectory of this business”. Perrigo’ was optimistic these approvals,namely generic ProAir (albuterol sulfate), “will come soon”, he said.“We believe it’s not a matter of if, it’s a matter of when.”

    To lead the proposed separation Perrigo has just re-appointedSharon Kochan as president of the Prescription business, six yearsafter transitioning him to become head of Perrigo’s Internationaloperation. Kochan, “an experienced operator who was instrumental inbuilding the Perrigo Rx segment from its infancy”, previously led thecompany’s US generics operation from 2005 to 2012.

    Perrigo’s Prescription sales slumped by 28.5% to US$179 millionin the three months ended 29 September, with the company blaming“challenging market dynamics in a number of authorised genericproducts”, a failure to launch new products and “customer servicechallenges” that resulted in lower volumes. Product discontinuationsalso wiped US$4 million from Perrigo’s top line.

    Increased spending on research and development contributedtowards amore severe decline in Prescription’s profitability, the business’operating profit plummeting by 56.1% to US$36 million. This producedan operating margin that was 12.7 percentage points lower at 20.1%.

    “The Rx segment continued to underperform,” underlined RonWinowiecki, Perrigo’s chief financial officer. He noted that price erosionfor the firm’s extended topical products, which comprise “approximately85% of Perrigo’s Prescription net sales”, was “in line with ourexpectations for the quarter”.

    A combination of price erosion and “poor customer service incertain key products” are among three factors that have led Perrigoto again slash its full-year Prescription net sales guidance. Turnoveris now expected to be US$800 million, down from US$880 millionguided in quarter two, and US$1.03 billion earlier this year.

    Perrigo also pointed to the firm’s lower expectations for genericAndroGel 1.62%, which the firm launched in mid-October to whatWinowiecki described on the call as aggressive competition from anauthorised generic (Generics bulletin, 19 October 2018, page 18).

    Akey priority for the Prescription business remains the successfullaunch of the firm’s generic ProAir. “We had a complete responseletter (CRL) that was issued this summer,” Winowiecki remindedinvestors. “We responded to that CRL. We’re not going to provideupdates, consistent with our practice, on the FDA’s process.”

    With group sales down by 8% to US$1.13 billion and a sizeableimpairment charge not linked to Prescription producing a US$122million operating loss,Winowieckimade clear “We are not satisfiedwithour overall performance results.” Corrective actions are “under way”, heinsisted. “Perrigo has undergone an immense amount of organisationalchange over the last few years, and with the planned separation of the Rxbusiness, we continue to evolve as an organisation.” Gn [email protected]

    BUSINESS STRATEGY/FIRST-QUARTER RESULTS

    Lannett will axe 250under savings schemeLannett will slash its workforce by around a fifth, representing morethan 250 employees, as part of an ongoing cost-reduction plan that isgeared towards reducing company expenses by approximately US$66million on an annualised basis by its financial year ending in June 2020.

    “This US$66 million reduction equates to more than 25%of our expense base,” chief executive officer Timothy Crew toldinvestors during Lannett’s first-quarter earnings call. It would beachieved, he noted, by selling the firm’s Cody Laboratories activepharmaceutical ingredient (API) business, ceasing operations at thefirm’s Philadelphia plant and distribution centre and reducing selling,general and administrative (SG A) expenses. Thus far, US$8 millionof savings have been achieved.

    Around a fifth of the 250 staff have already been let go, and two-thirds have been notified. Approximately half of these are from Cody,Lannett said. The remaining 15% of staff was “in-process” notedthe firm, which identified its branded salesforce as an area wherereductions will take place.

    Crew disclosed that half of the overall savings will be reinvestedback into Lannett. Of the US$33 million identified, US$15 millionwill go towards expanding capacity at the former Kremers Urbansite in Seymour, Indiana US$9 million in finished-dosage researchand development (R D) projects and the remaining US$9 millionfor SG A expenses. “With the reinvestment of some of the expensereductions, our overall level of R D will not be substantially reducedand abbreviated new drug application- (ANDA-) specific projectspending is expected to increase,” Crew stated.

    Reducing costs has climbed to the top of Lannett’s agenda, giventhe company’s US$827 million debt as of 30 September. To thatend, the firm has just “locked in US$50 million of gross profit” byagreeing to supply Amneal from 1 December on an exclusive basiswith levothyroxine sodium tablets until Lannett’s sourcing deal withJerome Stevens transfers to Amneal on 23 March.

    Losing the levothyroxine deal and writing off assets linked to theplanned sale of Cody caused Lannett to record total asset-impairmentcharges of US$369 million in its financial first quarter ended 30September 2018. This led to a US$342 million operating loss –versus against a prior-year US$40.7 million profit – on turnover thatalmost stagnated at US$155 million, as fluctuating sales of the firm’stherapeutic portfolio counterbalanced one another.

    But Lannett anticipates that the 16 products it has launched since 1January will contribute greater than US$75 million to its top-line in its2018-2019 financial year,while dedicated efforts that have “significantlyexpanded” Lannett’s pipeline will enable the firm to “continue our rateof product launches as well as diversify our business”.

    Apipeline of over 60 projects has been built by the firm, comprisingan equal split of more than 20 products that have been approved but notlaunched, products pending approval and active development projects.Beyond Lannett’s ownANDAportfolio, Crew revealed that its efforts todevelop an alternative to Sanofi’s Lantus (insulin glargine) with partnerChina’s HEC Group “also continues to progress, and we expect all pre-clinical work to be completed in financial year 2019”.

    Outside of these strategic moves, Lannett was still looking at a“range of options” for the company’s debt and capital structure. “It isa priority of this team and our board to address questions around ourcapital structure expeditiously, while we still have plenty of time to doso,” Crew insisted. Gn [email protected]

    Gen 16-11-18 Pgs.1-16.indd 3 14/11/2018 16:49

  • 4 bulletin 16 November 2018

    COMPANY NEWS

    [email protected]

    Issue 376 l 16 November 2018

    Director of Subscriptions: Val Davis Group Sales Manager: Rob Coulson

    Awards Manager: Natalie Cornwell Production Controller: Debi Robinson

    Head of Pharma: Mike Ward Managing Director: Philip Jarvis

    l General enquiries: [email protected] l Subscription enquiries: [email protected]

    l Editorial enquiries: [email protected] l Advertising enquiries: [email protected]

    [email protected]

    [email protected]

    Assistant Editor: Dean Rudge

    [email protected]

    Business Reporter: Grace Montgomery

    Terms & Conditions: See www.generics-bulletin.com/subscribe.While due care has been taken to ensure the accuracy of information contained in this publication,the publisher makes no claim that it is free of error and disclaims any liability whatsoever for anydecisions or actions taken as a result of its contents.

    Published by OTC Publications Ltd, 4 Poplar Road, Dorridge, Solihull B93 8DB, UK.Tel: +44 (0) 1564 777550 Fax: +44 (0) 1564 777524Company registered in England No 02765878.

    © OTC Publications Ltd. All rights reserved.Generics bulletin is registered as a trademark in the European Community.Printed by Warwick Printing Company Ltd.

    ISSN 1742-0784

    BUSINESS STRATEGY/THIRD-QUARTER RESULTS

    ANI eyes more dealsto follow WellSpringANI Pharmaceuticals is looking for further deals to accompanythe US firm’s organic growth, according to president and chiefexecutiveArthur Przybyl. InAugust, ANI acquired for US$18 millionCanada-based WellSpring Pharma Services, in a bid to expand itscontract manufacturing and development business, and to increasethe US firm’s capacity to re-commercialise its pipeline of ANDAsthat require a technology transfer from its local Baudette facility inMinnesota (Generics bulletin, 31 August 2018, page 14).

    “We are currently integrating that business,” ANI chief ArthurPrzybyl stated, “and look forward to making further use of themanufacturing facility to advance work on our pipeline products.”Furthermore, he added, “we continue to seek acquisitive opportunitiesto augment our internal growth”.

    Key pipeline products for ANI include generic versions ofJanssen’s Concerta (methylphenidate) extended-release tablets andBoehringer Ingelheim’s Aggrenox (aspirin/dipyridamole) extended-release capsules, that the firm intends to launch by the end of March2019 and “no later than 1 October 2019” respectively.

    ANI has also been granted priority review status for an undisclosedabbreviated new drug application (ANDA) filing. The product – whichhas an annual market value of US$46 million – has been assigned aGeneric Drug User Fee Amendments (GDUFA) date of April 2019.

    In the third quarter of 2018, group sales rose by 5% to US$50.7million, despite declines for both generics and brands.

    The US firm’s generics sales fell by 1% to US$30.3 million,“primarily due to volume decreases for fenofibrate, nilutamide andestrogens/methyltestosterone (EEMT)”, althoughANI noted that this wastempered by the launch of ezetimibe/simvastatin in the second quarter.

    ANI launched three generics during the past three monthsauthorised generics of Brethine (terbutaline sulfate) andAtacand HCT(candesartan hydrochlorothiazide), along with cholestyramine. So farin 2018, the firm has launched seven generics. The group noted thatthis had increased its current commercialised portfolio to a total of 31products. While the firm’s branded products turnover slid by 7% toUS$14.6 million, ANI’s contract-manufacturing sales leapt by 55% toUS$2.8 million. Royalties and other income increased from US$0.1million to US$3.0 million.

    Reiterating its previously announced 2018 sales forecast, ANIcontinues to expect full-year sales to reach US$195-US$205 million.G

    FIRST-HALF RESULTS

    PPIs place pressureon Chemiphar salesDouble-digit declines in sales of the lansoprazole and rabeprazoleproton-pump inhibitors (PPIs), along with similar slides in turnoverfrom donepezil, limaprost alfadex and voglibose, caused NipponChemiphar’s Generics sales to fall by 4.1% to 14.0 billion (US$123million) in the six months ended 30 September 2018.

    While all of the Japanese group’s leading generics showeddeclines in the first half of its 2018-2019 financial year ending March2019, turnover from its best-selling drug, amlodipine, largely held up,with sales down by just 0.5% to 1.43 billion. Cardiovascular andrespiratory drugs accounted for just over a third of group turnover.

    Chemiphar’s group turnover slid by 5.0% to 16.6 billion, almost1.0 billion short of its six-month forecast of 17.6 billion.And despiteresearch and development spending down by 14.2% to 985 million,the group’s operating profit tumbled by a third to 655 million.

    Following the first-half shortfall, Chemiphar has cut its full-yearturnover forecast by 1.0 billion to 34.5 billion, but retained itsoperating profit outlook of 1.10 billion. G

    Managing Editor: David WallaceExecutive Editor: Aidan Fry

    SECOND-QUARTER SALES

    Formulations rise boosts NatcoNatco said growth in both its domestic and export Formulationsbusinesses helped boost the Indian firm’s group sales by over athird to Rs5.84 billion (US$80.5 million) in the company’s financialsecond quarter ended 30 September 2018. Indian formulations salesstood at Rs1.94 billion, while exports reached Rs2.48 billion. Makingup over a tenth of sales was active pharmaceutical ingredients (API)turnover at Rs668 million. The group’s pre-tax profit more thandoubled to Rs2.35 billion.

    Highlighting “near-term strategies” in its complex generics andexports markets, Natco said it would focus on growth in its “keysubsidiaries” in Canada and Brazil. Natco also aims to intensifyfilings in rest of world markets led by its Hepatitis C portfolio.

    Long-term strategies for these businesses include “focusing on aselect few high-potential filings, predominantly differentiated productsthrough either novel drug delivery systems or complex chemistries”,as well as seeking strategic alliances in rest of world markets. G

    Gen 16-11-18 Pgs.1-16.indd 4 14/11/2018 16:49

  • 5bulletin16 November 2018

    COMPANY NEWS

    Figure 1: Breakdown by business segment of Gedeon Richter’s sales in the firstnine months of 2018 (Source – Gedeon Richter)

    Business segment Nine-month sales(€ millions)Change(%)

    Proportionof total (%)

    European Union1 281.1 -8.1 28

    Russia/CIS 273.0 -13.4 27

    Hungary 88.4 +0.3 9

    US 79.9 +20.2 8

    China 68.6 +12.8 7

    Latin America 13.4 -15.7 1

    Rest of World 43.7 +4.8 4

    Pharmaceuticals 848.1 -5.2 83

    Wholesale & Retail 190.4 -10.2 19

    Other/Eliminations -17.6 – -2

    Gedeon Richter 1,020.9 -5.8 1001 excluding Hungary

    NINE-MONTH RESULTS

    Richter drops despiterise in Bemfola salesSales of Bemfola (follitropin alfa) increasing by over a fifth to 30.6million (US$34.4 million) in the first nine months of 2018 was notenough to prevent Gedeon Richter’s total Pharmaceuticals turnoverfrom sliding by 5.2% to 848 million in the first nine months of2018. The group acquired global rights, excluding in the US, to thebiosimilar of Merck Serono’s Gonal-f in 2016.

    Bemfola achieved “higher sales” in Spain, a “good performance”in France and “a better performance” in Italy, but the product’s overallrise of 22.4% was unable to prevent turnover in Richter’s Women’sHealthcare portfolio from declining by 12.3% to 308 million. Thedecrease can be largely attributed to the firm’s Esmya (ulipristalacetate) women’s healthcare brand, which saw its sales tumble by67.6% to 21.9 million. Lower sales of the drug were reported inGermany, Spain, Italy, the UK, and Latin America.

    In late August, Richter commenced the “focused relaunch” ofEsmya in European markets, shortly after the European Commissionadopted an opinion from the committee for medicinal products forhuman use (CHMP) recommending measures to minimise the risk ofrare but serious liver injury (Generics bulletin, 10August 2018, page 9).

    As Figure 1 shows, Richter’s Pharmaceutical sales in the EuropeanUnion (EU), excluding Hungary, fell by 8.1% to 281 million. Thisincluded turnover in Poland and Romania that both inched up by 0.8%,to 60.4 million and 25.0 million respectively.

    Pharmaceuticals sales in Russia and the Commonwealth ofIndependent States (CIS) slipped by 13.4% to 273 million, offsettingdouble-digit growth in the US and China. The Hungarian firm’sdomestic market saw its turnover lift by 0.3% to 88.4 million, whilein Latin America, sales dropped by 15.7% to 13.4 million.

    Making up nearly a fifth of group turnover were Wholesaleand Retail sales that slid by 10.2% to 190 million. Richter said thiswas due to the temporary suspension at its Romanian wholesalersubsidiary, Pharmafarm, that was regranted a business licence inSeptember after the licence was revoked three months prior to that “inresponse to a breach of good distribution practice” (Generics bulletin,28 September 2018, page 4). “Most of the warehousing facilitiesof the Romanian wholesaler subsidiary resumed operations by 19September 2018,” the firm noted. Gn [email protected]

    MANUFACTURING/THIRD-QUARTER RESULTS

    Akorn site hit with 11observations by FDAAkorn has suffered a further manufacturing setback after the USFood and Drug Administration (FDA) issued the US firm’s localmanufacturing facility in Somerset, New Jersey, with a 22-page ‘Form483’ inspection report highlighting 11 observations.

    An audit that took place from 23 July to 30 August found thatbatches of azelastine 0.05% ophthalmic solution had failed controlled-room temperature stability testing, according to the report recentlypublished by the agency. The FDA also said that responsibilities andprocedures applicable to the quality-control unit “are not in writingand fully followed”, while laboratory records – as well as the cleaningand maintenance of equipment – were deemed “deficient”.

    “Laboratory controls do not include the establishment ofscientifically sound and appropriate test procedures designed to assurethat drug products conform to appropriate standards of identity, strength,quality and purity,” the FDA continued. Furthermore, proceduresdesigned to prevent microbiological contamination of sterile drugs “didnot include adequate validation of the aseptic process”.

    Akorn said it had “submitted a robust response” to the Form 483report concerning the Somerset site. “We are on schedule with ouraction items and have made good progress already, with approximately45% of our action items completed.”

    The company earlier this year received a Form483 for itsUS sterilefacility in Decatur, Illinois, that highlighted observations includinginadequate aseptic controls and cleaning procedures (Genericsbulletin, 3 August 2018, page 1). Stating that it had completed 80% ofthe remaining action items, Akorn said it was on track to complete themajority of the remaining items by the end of 2018.

    The firm revealed that so far in 2018, data-integrity assessmentand remediation efforts had resulted in expenses of US$23.7million, including US$22.4 million allocated to selling, general andadministrative (SG A) expenses and US$1.3 million to cost of goods.

    AtUS$63.2million, total SG Aexpenses for the quarter includedUS$9.4 million legal expenses linked to litigation in Delaware overan abandoned takeover bid from Fresenius Kabi. Oral arguments willbe heard by Delaware’s Supreme Court on 5 December after Akornappealed a recent US court ruling that absolved Kabi of completingits US$4.75 billion merger with Akorn after discovering compliancedeficiencies (Generics bulletin, 26 October 2018, page 3).

    In the thirdquarter, increasedSG Aand researchanddevelopmentexpenses, as well as higher litigation ruling and settlement costs,caused Akorn’s total operating expenses to advance by 49.7% toUS$133 million. This led the firm to report an operating loss ofUS$76.0 million on group sales that slid by 18.2% to US$166 million.

    Domestic sales fell by almost a fifth to US$162 million.Making up the majority of group turnover – 90% – was PrescriptionPharmaceuticals, that declined by 20.6% to US$148 million, whileConsumer Health sales rose by over a tenth to US$17.2 million.

    Akorn said its sales dropped largely due to the “effect ofcompetition on key products such as ephedrine sulfate injection,lidocaine ointment, methylene blue injection and Nembutal(pentobarbital)”. The company’s gross profit decreased by two-fifthsto US$57.3 million as a result of “increased operating costs associatedwith FDA compliance-related improvement activities, unfavourablevariances due to decreased production resulting from a plannedmaintenance shutdown at our Decatur manufacturing facility, as wellas unfavourable product mix shifts”. Gn [email protected]

    Gen 16-11-18 Pgs.1-16.indd 5 14/11/2018 16:49

  • 6 bulletin 16 November 2018

    COMPANY NEWS

    30 Januaryn 12th Pharmacovigilance Conference

    London, UKThis is a one-day Medicines for Europe conference which will lookat latest trends and the future direction of pharmacovigilance.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

    31 January-1 Februaryn 18th Regulatory & Scientific

    Affairs ConferenceLondon, UKThis conference will follow the Pharmcovigilance event at the samevenue and will provide updates on regulatory developments.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

    4-6 Februaryn Access 2019! AAM Annual Meeting

    New Orleans, USAThe Association for Accessible Medicines annual meeting will lookat the future of the generics and biosimilars industry.Contact: Association for Accessible Medicines. Tel: +1 202 249 7100.E-mail: [email protected]. Website: www.accessiblemeds.org/events.

    25-26 Februaryn EuroPLX 69

    London, UKThis two-day meeting provides an opportunity to discuss andnegotiate agreements, development, in-licensing, marketing,promotion and distribution.Contact: RauCon. Tel: +49 6221 426296 0.E-mail: [email protected]. Website: www.europlx.com.

    3-5 Marchn World Biosimilar Congress USA

    San Diego, USAThis meeting is co-located with a multi-streamed conferenceand technology exhibition. Topics covered will include marketaccess, clinical trials, legal considerations, development andmanufacturing and biosimilar regulatory guidelines.Contact: Terrapinn. Tel: +44 207 092 1210.E-mail: [email protected]. Website: www.terrapinn.com.

    26-27 Marchn 15th Legal Affairs Conference

    Amsterdam, The NetherlandsThis Medicines for Europe event will cover the latest developments inIP, legal affairs, biosimilars and the SPC Regulation.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

    EVENTS – January – March 2019

    SAVE THE DATE.....e G Generics i si i rs r s

    i e e n e er in r n r Ger n

    BUSINESS STRATEGY/THIRD-QUARTER RESULTS

    Endo eyes the futureand shuns shortagesEndo has no appetite for “going back and redeveloping” injectabledrugs that are in short supply, because the firm’s focus remains onhigher-value “technically-challenging products” and paragraph IVpatent-challenge opportunities, according to the company’s presidentand chief executive officer, Paul Campanelli.

    “When I see drug shortages on the injectables side, I don’t see thatas an opportunity necessarily for a company like Endo/Par,” Campanellitold investors during Endo’s third-quarter earnings call. “Typically,when I see drug shortages, a lot of times it’s because products are at alow cost or they’re not profitable.”

    Endo, he said, was looking at opportunities “on a go-forwardbasis,” evidenced by the pending acquisition of US generic sterileinjectables and ophthalmics specialist Somerset Therapeutics andthe firm’s internal research and development efforts. The Somersettransaction is on track to close in the first quarter of 2019.

    Lucrative brands for which Endo has settled litigation overits proposed generics include Dexilant (dexlansoprazole), Afinitor(everolimus), Ciprodex (ciprofloxacin/dexamethasone), Amitiza(lubiprostone), Kuvan (sapropterin) and the Mitigare (colchicinecapsules) 505(b)(2) hybrid, pipeline data reveals.

    Launching an authorised generic of Takeda’s branded colchicineoriginal, Colcrys, reduced the severity of several challenges for Endo’snon-injectable US Generics business during the third quarter. Salesfell by 12% to US$258 million, in light of pricing and competitivepressures, as well as product discontinuations. But Endo “actuallyoverperformed in the third quarter on Generics,” compared to priorexpectations, the firm noted, buoyed also by “delayed competition ona number of our key products in that portfolio.”

    “We expect our full-year 2018 US Generics revenue to declinein the mid-30s percentage range,” Endo noted, with the assumptionof potential new competition to certain key products. Echoingprevious comments, Campanelli added that Endo continued to be“encouraged that the downward pressures that we’ve experienced,”in the US generic retail market “over the past few years appear to bestabilising. We have seen promising early signals.”

    Launching an authorised generic of the Invanz (ertapenem)injectable, coupled with the “continued strong growth of Adrenalin(epinephrine) and Vasostrict (vasopressin),” saw US Branded SterileInjectables sales climb by 17% to US$237 million (see Figure 1).The Invanz authorised generic contributed US$26 million, followingmarket entry on 26 July.

    Endo fell to a US$12.7 million group operating loss, versus aUS$2.4 million loss the previous year, after being stung with asset-impairment charges totalling US$142 million. Gn [email protected]

    Figure 1: Breakdown by business segment of Endo International’s sales in the thirdquarter of 2018 (Source – Endo)

    Business segment Third-quarter sales(US$ millions)Change(%)

    Proportionof total (%)

    US Generics 258 -12 35

    US Branded SterileInjectables 237 +15 32

    US Branded Specialty& Established 220 -6 29

    International 30 -46 4

    Endo 745 -5 100

    Gen 16-11-18 Pgs.1-16.indd 6 14/11/2018 16:49

  • 7bulletin16 November 2018

    BUSINESS STRATEGY/THIRD-QUARTER RESULTS

    Amneal sees uptakedynamics changingOriginator companies in the US are “getting aggressive in terms ofrebating, aggressive in terms of contracting” resulting in a slowershare ramp-up for generic competition, particularly around complexproducts, according to comments made by Amneal’s president andchief executive officer Rob Stewart.

    “Traditionally, you just saw rapid substitution and uptake,”Stewart said during Amneal’s third-quarter earnings call. “But now Ithink that the dynamics are slightly different. The ramp-up is a littlebit slower than what we have traditionally seen, and I think that’sgoing to be the case going forward.”

    Amneal, hepledged,wouldcontinue to find“creativewaysaround”originator moves stymying generic uptake for complex generics andbiosimilars. Namechecking Copaxone (glatiramer acetate), for whichAmneal has plans to submit a generic filing, Stewart said “Thereneeds to be a little bit more sales and marketing support behind theseproducts. It’s not just ‘throw it out there and allow it to be substituted’.ou need to put some conditioning in the market.”

    “ ou need to make people aware of the interchangeability. Andpatient support services are needed on some of these products as well.So, I think you’re going to continue to see that play out as the marketmatures around some of these more complex products.”

    Stewart refused to comment on the current status of Amneal’sCopaxone application, going only so far as to confirm that it was not inthe firm’s 2018 guidance. “But when we talk about 2019, we’ll updateyou on kind of what’s in and what’s out. I’ll continue to be a bit stealthyon some of our pipeline opportunities,” he said, “purely because of thefact that there is a competitive advantage to not sharing too much.”

    Launching 27 generics since 1 January was not enough to rescuethe recently-combined Amneal-Impax operation from a sales declinein the third quarter. Amneal’s Generics sales fell by 3.6% to US$391million, on the back of supply issues for the firm’s epinephrineauto-injector, lower sales of generic Tamiflu (oseltamivir), increasedcompetition and product discontinuations.

    A US$44 million contribution from new product launchescoupled with higher sales of the firm’s uvafem (estradiol) genericof Vagifem helped mitigate these factors. Meanwhile, Amneal wascontinuing to “work closely with Pfizer in order to receive the supplyneeded to meet the demand” for epinephrine. The Generics business’operating profit leapt by 28% to US$92.2 million, but this was purelybecause the legacy Impax business had suffered a US$21.5 millionoperating loss in the third quarter of 2017.

    From 1 December this year, Amneal will begin supplying JeromeStevens Pharmaceuticals’ levothyroxine product in the US, under arecently-revised agreement (see page 3) initially struck in August.Another licensing deal announced shortly after gives the company USaccess to American Regent’s preservative-free generic alternative toMakena (hydroxyprogesterone caproate). “Additional opportunitieslike these to fuel growth is an important part of our strategy,” Stewartcommented, “and remains a top priority going forward.”

    Amneal had, meanwhile, made “excellent progress with theintegration ofAmneal and Impax,” Stewart claimed. “We are well aheadof schedule and key deliverables, including the closure of the Hayward,California, facility, which is expected to be completed within one yearof the merger. All of the major initiatives linked to synergies have beencompleted and we’re on track to achieve more than US$200 million incost synergies at an accelerated pace.” Gn [email protected]

    MERGERS & ACQUISITIONS/RESULTS FORECAST

    Hikma makes a movefor Vietnam’s MedlacHikma has struck a deal to acquire injectables manufacturingspecialist Medlac Pharma Italy, an Italian-Vietnamese joint venturebased in Vietnam. “The acquisition includes a high-quality injectablesfacility, adjacent vacant land, Medlac’s product portfolio of 23injectable products, its pipeline and all employees,” the Jordanianfirm stated. No financial details or closing conditions were disclosed.

    “The acquisition provides Hikma with a foothold in Vietnam,one of the most dynamic emerging markets in Asia,” Hikma noted.“Driven by a growing population, government healthcare reforms andstrong economic development, Vietnam has been the fastest-growingpharmaceutical market in south-east Asia in recent years, and thisfast-paced growth is expected to continue.”

    Riad Mechlaoui, Hikma’s president of injectables, said he was“very pleased to have reached an agreement to acquire Medlac”.“Vietnam is an attractive market with significant growth potential,”he outlined. “We are confident that by leveraging Hikma’s globalexpertise, we can add significant value to Medlac’s business.”

    Founded in 2008, Medlac Pharma Italy operates a facility locatedin Hoa Lac High-tech Park, in the Thach That district of Hanoi. Billingitself as “one of the few factories which produce pharmaceuticals ininjection forms in Vietnam”, Medlac says its plant “is equipped withmodern high-tech and automatic machinery imported from Italy andGermany at World Health Organization (WHO) good manufacturingpractice (GMP) standards”.

    Medlac’s facility produces for both and for export, having gainedits first marketing authorisations at the end of 2012. Its products cover14 international non-proprietary names (INNs) in powder, lyophilisedpowder, solution and solvent forms. In particular, Hikma said, Medlachad “built a strong reputation as a high-quality manufacturer in theareas of anti-infectives and cardiovascular”.

    Hikma’s announcement of the Medlac deal came as the firmannounced a business update for the remainder of 2018 that includedraising its full-year guidance. “We are delivering revenue growth and,more importantly, improving profitability ahead of our expectationsin both our Generics and Injectables businesses,” commented chiefexecutive officer Siggi Olafsson.

    Amid a “challenging” US retail market for the non-injectableGenerics segment, Hikma said the “recent commercial and operationalimprovements we have made to our business are enabling us to deliverstrong growth from our more differentiated portfolio”, with recentlaunches that included a first-to-file Paragraph IV product.

    Citing “good progress with our cost-reduction initiatives,including the consolidation of our manufacturing and distributionfacilities”, Hikma said this was “supporting the strong improvement inthe profitability of our Generics business this year”. The firm forecastsfull-year Generics sales of US$675-700 million with a core operatingmargin in the low teens.

    For the Injectables unit, increased competition in the US hadbeen offset “through the breadth and resilience of our portfolio, gooddemand for recent launches and our ability to leverage our scale andflexibility to respond to market shortages”. Strong European demandfor recently-acquired products, growth in Saudi Arabia and increasedbiosimilar sales also supported forecasted full-year sales total ofUS$825-850 million, with a 39%-40% core operating margin.

    Meanwhile, Hikma has just struck a deal with Vectura to developrivals to GlaxoSmithKline’s Ellipta inhalers portfolio (see page 15).Gn [email protected]

    COMPANY NEWS

    Gen 16-11-18 Pgs.1-16.indd 7 14/11/2018 16:49

  • 8 bulletin 16 November 2018

    COMPANY NEWSFIRST-HALF RESULTS

    US and India drive upprofits for WockhardtHigher sales driven by double-digit increases in the US and Indiaresulted in increased profits for Wockhardt in the company’sfinancial first half ended 30 September 2018.

    Insisting that its overall business had “showed markedimprovement”,Wockhardt reported sales in India – where six productswere launched during the financial first half – that increased by 13%to Rs8.50 billion (US$117 million).

    At the same time, turnover leapt by almost a fifth to Rs3.69 billionin the US (see Figure 1), “mainly on account of new product launchesand increased market share of some products”.Wockhardt received onenew abbreviated new drug application (ANDA) approval during thefirst half, taking its total approved ANDAs to 71 as of 30 September.

    And in Wockhardt’s Emerging Markets region, turnover jumpedby more than half to Rs2.63 billion, representing more than a tenth ofthe Indian company’s overall group sales.

    Europe, however, told a different story, with sales slipping by 3%overall to Rs6.52 billion. In the UK – whereWockhardt “launched twonew products, received one new approval and successfully filed twonew products during the first half” – sales dropped by 4% to Rs4.89billion, although in local-currency terms the drop was significantlysteeper at 12%. This offset 10% growth to Rs330 million in France, aswell as an increase in Ireland of 18% to Rs860 million that translatedto a 7% rise in euro terms.

    Remedial measures hit profits“The increase in revenues, coupled with the company’s ongoing

    focus on cost optimisation resulted in an improved earnings beforeinterest, tax, depreciation and amortisation (EBITDA),” the companyobserved, even though “costs of ongoing remedialmeasures continuedto impact profitability”.

    Wockhardt registered EBITDA of Rs810 million in the first half,compared to a Rs710million EBITDAloss in the prior-year period. Staffcosts were 3% higher at Rs4.47 billion, while research and developmentspending was reduced by 4% to Rs1.43 billion. Other spending jumpedby 6% to Rs5.53 billion.

    Recently, Wockhardt announced plans for the Indian company to“grow and further establish its international presence in pharmaceuticalmanufacturing” by setting up a manufacturing plant for new chemicalentities (NCEs) in Dubai, United Arab Emirates (Generics bulletin, 3August 2018, page 5). Gn [email protected]

    Figure 1: Breakdown by region of Wockhardt’s sales in its financial first half ended30 September 2018 (Source – Wockhardt)

    RegionFirst-Half Sales(Rs millions1)

    Change(%)

    Proportionof Total (%)

    India 8,500 +13 40

    UK 4,890 -4 23

    Ireland 860 +18 4

    France 330 +10 2

    Other 440 - 2

    Europe 6,520 -3 31

    US 3,690 +19 17

    Emerging Markets 2,630 +52 12

    Wockhardt 21,330 +12 1001 rounded to nearest Rs10 million

    DR REDDY’S has revealed that German authorities concludeda n i of the Indian firm’s local formulationsmanufacturing plant in Duvvada, Vishakhapatnam, on 9 November.“The facility is considered compliant and the European Union(EU) good manufacturing practice (GMP) certification continuesto remain active with one specific exclusion of a new product,”Reddy’s stated, adding that it would submit a detailed correctiveand preventive action plan (CAPA) to the authorities. The site wasrecently issued with eight ‘Form 483’ observations following aUS Food and Drug Administration (FDA) inspection (Genericsbulletin, 2 November 2018, page 3).

    CIPLA subsidiary InvaGen Pharmaceuticals has entered into“definitive agreements with two closing stages” for a r sec isi i n en e er e ics, a Fortress Biotech companyfocused on the development and commercialisation of intravenoustramadol. Upon first stage closing, InvaGen will acquire a 33.3%stake in Avenue on a fully diluted basis for US$35 million. Uponsecond stage closing, the firm will purchase the remaining issuedand outstanding shares of Avenue pursuant to a merger transactionfor up to US$180 million, and following this, Avenue shareholderswill receive certain contingent value rights relating to certain annualnet sales and gross profits of tramadol. The transaction is subject tostockholders’ and regulatory approvals, and other conditions.

    HYPERA PHARMA said that both market growth and thecompany’s initiatives to increase its production capacity in its‘Similars Generics’ business unit aided a r rn er rise

    to BRL949 million (US$252 million) in the third quarterof 2018. The segment’s growth “came mainly from price increasesand volume expansion in the period”, Hypera noted. Sales growthbenefited from the performance of both generics and “leadingbrands” Neosoro, Flavonid and Doralgina.

    ALEMBIC has been issued r r r ce rser i ns by the US Food and Drug Administration (FDA)

    following a pre-approval inspection conducted at its oral-solidformulations facility in Panelav, India, from 22-26 October.Alembicsaid it would provide a “comprehensive corrective action report toaddress each observation”.

    PODRAVKA’S Pharmaceuticals s es r se to HrK639million (US$96.9 million) in the first nine months of this year, helpedby growth of almost a fifth to HrK127 million in Eastern Europe dueto “increased demand for the Prescription drugs category”. A 12.8%rise to HrK44.5 million in Central Europe was led by “increaseddemand and the launch of new products in Poland, the CzechRepublic and Slovakia”, while sales in the Croatian group’s domesticAdria region inched up by 1.2% to HrK458 million. This offset aslide in the Western Europe and Overseas region, that slumped byalmost three-fifths to HrK0.8 million.

    MAYNE PHARMA’S Metrics Contract Services division hasannounced the s ccess i ic i n c erci inines for serialisation at its new US$80 million oral-solid dose USmanufacturing site in Greenville, North Carolina. Noting that onebottling line was dedicated for clinical packaging and two othercommercial lines had been qualified for serialisation,Metric stated that“packaging capacity has more than doubled” as part of the Greenvillesite expansion. “The newly-installed equipment includes a New Jerseymachine with an IMA automated case packer and palletiser,” the firmsaid. “The new commercial facility has space available to add a thirdcommercial packaging line as needed to support future growth.” G

    IN BRIEF

    Gen 16-11-18 Pgs.1-16.indd 8 14/11/2018 16:49

  • 9bulletin16 November 2018

    COMPANY NEWS

    FIRST-QUARTER RESULTS

    Chinese disruption isopportunity for AcetoDisruption among Chinese suppliers of ingredients as a result ofthe country’s ‘Blue Sky Protection Campaign’ to control pollution“has provided new growth opportunities” for Aceto, according tochief executive officer William Kennally. “Our long history, strongsupplier knowledge and relationships in this region have enabled usto respond to the additional needs of our customers,” he said, “asthey face challenges in securing the stability of their supply chains.”

    In Aceto’s financial first quarter ended 30 September 2018,Kennally pointed out, “our Pharmaceutical Ingredients andPerformanceChemicals segments delivered another quarter of steady sales growthand strong gross margins, demonstrating once again the consistent anddependable value this business brings to our customers”. PharmaceuticalIngredients sales rose by 6.2% to US$38.8 million while PerformanceChemicals turnover grew by 4.8% to US$44.7 million.

    However, this growth was offset by Human Health sales fallingby 23.7% to US$80.8 million, “due to lower sales at Rising resultingfrom persistent adverse conditions in the generics market, and delayedproduct launches”, leading to total turnover dropping by 11.3% toUS$164million. TheHumanHealth segment’s grossmargin fell by 12.7points to 10.5% due to “continued pricing pressure, intense competitionand related consolidation of customers, unfavourable product mix andfailure-to-supply charges at Rising” that came to US$6.5 million. Acetoreported an operating loss of US$13.3 million. G

    DIVESTMENTS/THIRD-QUARTER RESULTS

    Mallinckrodt mightdivide up GenericsMallinckrodt would consider splitting up the Specialty Genericsbusiness that it is currently holding for disposal into smallersections to support their divestment, according to the US-based group’schief executive officer, Mark Trudeau. “Certainly, we could sell thebusiness in parts,” he told investors. “We are exploring, and have, awhole range of strategic options in front of us, and we will continueto pursue all of those going forward.” “As that situation develops,whether it is a sale or any other option, we will certainly be updatingthe market at the appropriate time,” Trudeau promised.

    Towards the end of February this year, Mallinckrodt’s boardauthorised a process to begin to dispose of the firm’s Specialty Genericsbusiness segment, along with certain non-promoted brands and asupply agreement for contrast media and delivery systems (Genericsbulletin, 2 March 2018, page 1).

    InMallinckrodt’s financial third quarter ended 28 September 2018,these combined discontinued businesses – referred to by Mallinckrodtas its Specialty Generics Disposal Group – suffered a 17.3% fall inturnover to US$160 million, while their pre-tax profit tumbled byalmost two-thirds to US$13.5 million.

    Group turnover grew by 6.6% to US$640million, aided by a 6.0%rise in sales of the Inomax (nitric oxide) drug-device combination.Mallinckrodt expects resolution of its appeal against an adverse patentdecision on Inomax midway through next year. G

    Gen 16-11-18 Pgs.1-16.indd 9 14/11/2018 16:49

  • 10 bulletin 16 November 2018

    MARKET NEWSREGULATORY AFFAIRS

    Australia and Canadaallow API recognitionCertificates of good manufacturing practice (GMP) complianceissued by Health Canada and Australia’s Therapeutic GoodsAdministration (TGA) for active pharmaceutical ingredients (APIs)manufactured in their respective territories will enjoy reciprocalrecognition in support of GMP clearance applications, under anextension to amutual-recognition agreement between the two countriesthat has come into force from the start of November.

    In November 2013, Canadian regulatory amendments formandatory GMP of APIs intended for use in human drugs came intoforce in Canada. This enabled Health Canada to include APIs underexisting mutual-recognition agreements. Meanwhile, Australian APImanufacturers are regulated under 1989 and 1990 legislation.

    The existing mutual-recognition deal between the two countriesdates back to 2000 and has been operational since 2006. It covershuman pharmaceuticals, radiopharmaceuticals and biological drugsbut does not apply to pre-approval inspections.

    “Australian sponsors who sourceAPIs fromCanadawill continueto benefit from the existing mutual recognition agreement pathwaywhich requires a reduced level of documentary evidence, comparedto the compliance verification pathway,” the TGA pointed out.

    Meanwhile, Health Canada observed that “stakeholders fromCanadawill benefit fromtheexchangeofGMPcertificatesofcompliancebetween the TGA and Canada, therefore reducing regulatory burden toobtain information from their foreign buildings”.

    Canadian firms exporting drugs andmedicinal products toAustraliathat fall within the scope of the mutual-recognition agreement and thatare manufactured within Canada – as well as companies importing intoCanada such products that are manufactured in Australia – “benefitfrom specified GMP exemptions provided by the mutual-recognitionagreement”, Health Canada explained. G

    REGULATORY AFFAIRS/MANUFACTURING

    FDA steps up steriles auditsModernisedmethods for assessing, recording and reporting data fromsurveillance and pre-approval inspections for sterile injectablesfacilities are laid out under new rules unveiled by the US Food andDrug Administration (FDA).

    A New Inspection Protocol Project (NIPP) uses “standardisedelectronic inspection protocols to collect data in a structuredmanner”.This, the agency claims, allows for “more consistent oversight” ofsterile plants, as well as for “faster and more efficient analysis of ourfindings. The protocols also include additional questions related toquality culture observed in facilities,” the FDA adds.

    FDACommissioner Scott Gottlieb noted that the sterile injectablessector had “been the subject of sterility problems and shortages in thepast. With better and more consistent oversight of these manufacturingfacilities, we hope to be able to spot problems earlier and implementmitigation steps that can avert dangerous drug shortages.”

    The aseptic NIPP protocols – for which the agency conducted“multiple pilots” – would, Gottlieb revealed, be “the first of whatwe plan to be a series of valuable new inspection protocols coveringall dosage forms. As we integrate learnings from these pilots in ourfield activities,” he added, “our goal is to have them ready for fullimplementation within the next two years.” G

    DENMARK’S government intends to introduce e ern re erencericin for the section of the country’s drugs market not currentlycovered by voluntary pricing agreements. Health minister EllenTrane N rby observed that list prices for hospital medicines were10% lower in Sweden and 13% lower in Norway, while the costof hospital drugs in Denmark had risen by more than 50% overthe past decade to over DKr9 billion (US$1.35 billion). By settingceiling list prices based on benchmarking against prices in “nineselected countries”, the Danish government believes the reference-pricing scheme will foster competition among “200-300 foreignpharmaceutical companies that collectively achieve annual sales inDenmark of more than DKr6 billion”.

    BIOSIMILAR e c i n n r i n will be the focus ofa webinar organised by the US Center for Biosimilars on 13December. The “stakeholders summit”, which will take place atthree different times during the day, will involve a “lively peer-to-peer discussion” that will be moderated byAvalere Health’s GillianWoollett and will feature speakers from Pfizer and Sandoz.

    FRENCH competition regulator the Autorité de la Concurrence haslaunched a ic c ns i n n e icines is ri i n, withcomments open until 18 November. The initiative, which was firstheralded last year (Generics bulletin, 1 December 2017, page 1),covers issues suchasonlinedrugsales andsupply-chain intermediaries.The competition body intends to adopt a final opinion early next yearahead of “a second opinion on setting the price of medicinal products”inmid-2019.At the time of launch, the competition authority observedthat a previous opinion by the regulator had found that pharmaciesbenefit from “substantial discounts” on generics that were “only rarelypassed on to the final consumer”.

    US President Donald Trump has been r e s r e is i n“tolimitanti-competitive‘pay-for-delay’pharmaceuticalsettlements”in a letter sent by Democrat SenatorAmy Klobuchar and RepublicanSenator Chuck Grassley. The Senators are seeking backing for theirbipartisan S.124 Preserve Access to Affordable Generics Act thatwould authorise the US Federal Trade Commission (FTC) to initiateproceedings against parties that settle a patent-infringement claim.Such agreements would be presumed to be anti-competitive if thegeneric applicant receives anything of value and agrees to limit orforego research, development, manufacturing, marketing, or sales ofa generic drug. The bill would also amend the Federal Food, Drugand Cosmetic Act to forfeit generic 180-day exclusivity if the FTCor a court decides that an agreement violated the legislation.

    SWITZERLAND’S Federal Council says the country acted aslead negotiator in negotiating a ree r e ree en between theEuropean Free TradeAssociation (EFTA) and Indonesia. Revealingthat the negotiations had been “concluded in substance”, the Swisscouncil said texts were being finalised and the agreement wasscheduled to be signed before the end of this year. It claimed theSwiss pharmaceuticals and chemicals sectors were set to benefit.However, non-governmental organisations (NGOs) have voicedconcerns that intellectual-property provisions in the agreementwould “negatively affect Indonesian patients’ access to medicines”.

    ANMAT AND COFEPRIS – the medicines regulatory bodies inArgentina and Mexico – have reached an accord on exchanginginspection reports resulting from n c rin r c iceG ins ec i ns. The move towards developing “a unifiedmechanism” for validatingGMPaudits follows a broad commitmentmade in 2012. G

    IN BRIEF

    Gen 16-11-18 Pgs.1-16.indd 10 14/11/2018 16:49

  • 11bulletin16 November 2018

    REGULATORY AFFAIRS

    October brings ANDA recordAtotal of 23 first-time generics and 17 complex generics wereamong a record 110 final and 18 tentative abbreviated newdrug application (ANDA) approvals that the US Food and DrugAdministration issued during October this year. The 128 total approvalactions in October, as the agency began the second year of its seconditeration of the Generic Drug User Fee Amendments (GDUFA II)program, surpassed the previous record of 126 set in July this year.

    October’s 128 final or tentative approvals far surpassed the83 ANDAs that the FDA received during the month, according topreliminary figures from the agency that also show that it issued 175complete responses to ANDAs.

    Pointing out that the agency was “beginning the new fiscal yearby breaking another record”, FDA Commissioner Scott Gottliebsaid that by working to reduce the number of ANDA review cyclesthrough process efficiencies, the agency was “getting quality genericmedicines to Americans sooner”. At the end of the previous GDUFAand fiscal year, the FDA had 29 priority-review and 45 competitivegeneric therapy (CGT) ANDAs awaiting agency action. G

    INTELLECTUAL PROPERTY

    UK’s Supreme Court torule on obviousnessThe UK Supreme Court is about to consider “the correct testfor obviousness in the context of assessing the validity of apharmaceutical patent” following an appeal by Icos Corporation andEli Lilly in a case revolving around tadalafil that also includes Teva,Accord’s Actavis and Mylan’s Generics UK. A hearing is due to takeplace on 19-20 November 2018.

    In November 2017, the UK’s Court of Appeal ruled that the UKpart of European patent EP1,173,181 that protects a daily-dosageregimen of 5mg or less was obvious (Generics bulletin, 10 November2017, page 13), after a first instance judge had initially ruled againstthe generics firms, backing the originators.

    A last-minute attempt by Lilly and Icos to secure an injunctionpreventing the three generics firms from launching rivals to Cialis(tadalafil) 2.5mg and 5mg daily-use tablets in the UK failed shortlyafter, around the same time that a supplementary protection certificate(SPC) covering 10mg and 20mg tadalafil expired, opening up themarket to generics (Generics bulletin, 24 November 2017, page 11).

    TheUKBioIndustryAssociation (BIA)hasbeengrantedpermissionby the Supreme Court to intervene in the case, which the BIA believes“could have far-reaching impacts on the life sciences sector”.

    “TheBIAis arguing thatmedical innovations should be patentableirrespective of how the invention is made,” the association argued,noting that the tadalafil case addressed the patentability of a discoverymade during the dosage-regime testing stage of a clinical trial.

    Not ‘obvious to try’, Icos claims“Actavis has challenged the patent owned by Icos on the

    grounds that the discovery was obvious,” the BIA observed. “Actavisclaimed in the Court of Appeal that it would have been obviousstarting from a prior publication to reach the patented discovery – alow effective dose of tadalafil that shows reduced side-effects – duringrouting pre-clinical and clinical trials, rendering it unpatentable.”

    However, the BIA noted, “Icos argued that it would not havebeen ‘obvious to try’ the 5mg daily dose because at the start of thedevelopment process the skilled team would have no idea whether ornot such a dose would be safe and effective”.

    The BIA “highlights in its application to the Supreme Court thatthe design and conduct of clinical trials and other biomedical researchfrequently involves the application of significant skill and complexdecision-making, despite often following a step-wise well-establishedpath to ensure regulatory compliance”. It submits that “the assessmentof obviousness should be based around the knowledge at the relevanttime, and not simply on the nature and type of research which led tothe claimed invention”.

    Urging the Supreme Court “not to make a decision in thiscase that could have unintended consequences for other patents forinventions made during the pre-clinical or clinical trial process”, theBIA warns that such a decision would “significantly raise the hurdlefor companies to attract the investment needed to identify and developnew medical innovations”.

    BIAchief executive Steve Bates highlighted that “clinical trials arean important part of medical innovation, and it is vital that companiescan protect their discoveries regardless of what stage in the researchprocess they are made”. “Without a strong and consistent patentsregime that rewards innovation,” Bates cautioned, “UK biosciencecompanies will not be able to attract the investment they need.” Gn [email protected]

    REGULATORY AFFAIRS/PRICING & REIMBURSEMENT

    US midterm electionsto have major impactResults of the US midterm elections held in early November willhave a major impact on the generics and biosimilars industries,according to Chip Davis, president and chief executive officer of theUS Association for Accessible Medicines (AAM).

    “The midterm election results changed the political landscapein Washington and states across the country,” Davis outlined. “Thismeans that regulatory and policy proposals that will absolutely impactour industry are on their way in the next Congress. Fortunately, AAMis going to have a seat at the table for these debates.”

    In particular, Davis pointed out, three key figures – US PresidentDonald Trump, expected next speaker of the House of RepresentativesNancy Pelosi, and Senate majority leader Mitch McConnell – had “allstated that one area where they thought they could work together in abipartisan manner was to reduce prescription drug costs here in the US”.

    Recently, Trump unveiled plans to introduce an InternationalPricing Index (IPI) model in the US, as part of efforts to bring downprices (Generics bulletin, 2 November 2018, page 1).

    Separately, theAAM has announced that it and 28 other healthcaregroups–representingpatients, taxpayers, andhealthprofessionals–havesubmitted letters to US Trade Representative Robert Lighthizer, Healthand Human Services (HHS) secretary Alex Azar and Congressionalleaders “expressing concern that the US-Mexico-Canada Agreement(USMCA), if left in its current form, will keep drug prices high and outof reach of Americans”.

    This follows a letter to Lighthizer from the AAM in which theassociation claimed the trade deal would “exacerbate the laggingbiosimilarmarket in theUS”, slow biosimilar and generic development,and create inconsistencieswithUS law (Generics bulletin, 9November2018, page 11).

    Chief among industry concerns is a 10-year data-exclusivity periodfor biological drugs that was denounced by the Canadian, Mexican andUS off-patent industry associations in a joint statement at the time theUSMCAwas first agreed in principle. G

    MARKET NEWS

    Gen 16-11-18 Pgs.1-16.indd 11 14/11/2018 16:49

  • 12 bulletin 16 November 2018

    PRICE WATCH.....UK

    Figure 1 (above): Comparison between the periods 1-30 September 2018 and 1-31October 2018 of UK trade prices of the most recently-launched generics listed incategory M of the Drug Tariff of pharmacy-reimbursement prices. Averages calculatedfrom at least 24 data points. Figure 2 (top right) and Figure 3 (centre right): Biggestaverage trade-price changes between 1-30 September 2018 and 1-31 October 2018.Averages calculated from at least 16 data points. Figure 4 (bottom right): Ranking offastest-moving products subject to the most price offers made to independent UKpharmacists (one strength per ingredient; offers recorded by 31 October). Data forFigures 2, 3 and 4 from a basket of about 750 commonly-dispensed generics. Recently-launched products in Figure 1 excluded from Figures 2 and 3 (Source – WaveData).

    Aripiprazole tabs 10mg 28 £0.78 -11 £1.67 -19Carbimazole tabs 5mg 100 £17.99 -16 £27.16 -7Celecoxib caps 200mg 30 £0.83 +1 £1.37 +11Cilostazol tabs 100mg 56 £3.30 -1 £4.87 -2Duloxetine caps 30mg 28 £0.87 -7 £1.70 -22Eplerenone tabs 25mg 28 £2.99 -7 £5.28 -8Escitalopram tabs 10mg 28 £0.42 -5 £0.84 +12Etoricoxib tabs 90mg 28 £2.15 -4 £3.40 -14Ezetimibe tabs 10mg 28 £1.35 -6 £3.27 -8Frovatriptan tabs 2.5mg 6 £3.25 +18 £5.33 +1Ivabradine tabs 5mg 56 £4.05 -3 £8.36 -11Memantine tabs 10mg 28 £0.57 +4 £0.89 +6Nefopam tabs 30mg 90 £4.89 -2 £10.02 -8Nortriptyline tabs 10mg 100 £1.30 +4 £2.56 -11Olmesartan tabs 10mg 28 £0.65 -6 £1.22 -2Pregabalin caps 150mg 56 £2.20 -6 £3.98 ±0Rasagiline tabs 1mg 28 £1.07 -2 £2.31 -5Rizatriptan tabs 10mg 3 £3.58 -14 £6.39 -6Rosuvastatin tabs 5mg 28 £0.72 -3 £1.15 +1Sevelamer tabs 800mg 180 £23.15 ±0 £36.58 +31Sildenafil tabs 100mg 4 £0.23 ±0 £0.39 -5Tadalafil tabs 10mg 4 £0.97 +8 £1.67 -3Telmisartan tabs 80mg 28 £1.10 +25 £9.51 +649Travoprost drops 40µg/ml 2.5ml £2.10 -6 £4.02 -7Zonisamide caps 100mg 56 £2.62 -27 £6.22 ±0

    Omeprazole caps 20mg 28 138 147 139

    Simvastatin tabs 40mg 28 127 140 124

    Lansoprazole caps 30mg 28 128 120 118

    Atorvastatin tabs 20mg 28 139 133 116

    Bendroflumethiazide tabs 2.5mg 28 98 101 102

    Metformin tabs 500mg 28 103 101 102

    Fluoxetine caps 20mg 30 112 111 97

    Paracetamol caps 500mg 100 87 88 96

    Sertraline tabs 100mg 28 95 96 96

    Amitriptyline tabs 10mg 28 111 115 95

    Ondansetron tabs 4mg 30 £0.98 ±0 £17.66 +815Furosemide tabs 40mg 28 £0.14 +27 £0.74 +270

    Furosemide tabs 20mg 28 £0.14 +40 £0.72 +260

    Ibandronic acid tabs 50mg 28 £4.10 -4 £23.20 +217

    Telmisartan tabs 20mg 28 £0.89 +31 £2.97 +154

    Naproxen tabs 500mg 28 £0.90 +22 £3.55 +147

    Sumatriptan tabs 100mg 6 £2.88 -12 £4.52 -31

    Olanzapine tabs 7.5mg 28 £1.10 -8 £3.14 -30

    Metformin tabs 500mg 500 £4.33 ±0 £6.72 -29Flucloxacillin o/s 250µg/5ml 100ml £5.80 -6 £14.05 -24Pioglitazone tabs 30mg 28 £1.25 -24 £3.23 -22

    Sumatriptan tabs 50mg 6 £2.42 -17 £4.23 -21

    Up to the minute live retail market pricing is available for the UK and Eire on Wavedata Live at wavedata.net.

    Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125. E-mail: [email protected].

    RECENT LAUNCHESProduct/Strength/Pack size Lowest Change Average Change

    price (%) price (%)

    BIGGEST RISERSProduct/Strength/Pack size Lowest Change Average Change

    price (%) price (%)

    BIGGEST FALLERSProduct/Strength/Pack size Lowest Change Average Change

    price (%) price (%)

    FAST MOVERSPrice offers as at 31 October 2018

    Product/Strength/Pack size August September October

    WANT MORE LIKE THIS?

    October rises prompt concessions in the UKSteep price rises for several different generics prompted the UK’sDepartment of Health and Social Care (DHSC) to grant concessionsfor 25 molecules across 45 separate presentations in October.

    According to the latest figures from WaveData, ondansetron4mg tablets in 30-count packs saw their average price increase by815% to 17.66 (US$23.17) in October (see Figure 2). Although thepacks of 30 tablets were not included in the list of DHSC concessionspublished by the Pharmaceutical Services Negotiating Committee(PSNC), 10-tablet packs were granted a concession price of 16.59.

    Furosemide 40mg in 28-count packs saw a 270% averageleap to 0.74, prompting a concession of 2.49, although the 20mgpresentation that experienced a 260% jump to 0.72 did not featureon the PSNC list. Packs of 28 naproxen 500mg tablets that saw theiraverage price jump by 147% to 3.55 were granted a 5.00 concession,while the same pack sizes of allopurinol 100mg and 300mg tablets

    that saw increases of 142% to 1.50 and of 141% to 5.14 receivedconcession prices of 2.54 and 5.83 respectively.

    While telmisartan 20mg tablets in our ‘biggest risers’ and 80mgtablets in our ‘recent launches’ (see Figure 1) both experienced triple-digit average rises, only 40mg were granted concession.

    Chief among the fastest-falling average prices were sumatriptan100mg tablets in packs of six, which dropped by almost a third to4.52 (see Figure 3). Similar drops were experienced by olanzapine7.5mg tablets in 28-count packs and 500-tablet presentations ofmetformin 500mg.

    Omeprazole and simvastatin held onto their dominant positionsat the top of our table of ‘fast movers’ showing the number of offersin the marketplace (see Figure 4). Lansoprazole jumped up a coupleof places from September to overtake atorvastatin (Generics bulletin,26 October 2018, page 18). G

    Gen 16-11-18 Pgs.1-16.indd 12 14/11/2018 16:49

  • 13bulletin16 November 2018

    PRODUCT NEWS

    RESPIRATORY DRUGS

    Cipla rivals Seretide in FranceCipla’s rival to GlaxoSmithKline’s Seretide (fluticasone/salmeterol)125 g/25 g and 250 g/25 g have been added to France’s répertoireof substitutable generic equivalents.

    At the same time, France has added Arrow’s generic Ferriprox(deferiprone) 500mg and 1,000mg tablets to the répertoire, along withthe firm’s arelto (rivaroxaban) and Imovane (zopiclone) rivals.Teva hashad rivals to Celgene’s Revlimid (lenalidomide) capsules listed in 2.5mg,5mg, 10mg, 15mg and 25mg strengths, while multiple generic versionsof gefitinib 250mg tablets have been added alongside Astra eneca’sIressa brand. Krka’s perindopril/amlodipine 2.85mg/2.5mg and5.7mg/5mg rivals to Servier’s Amplival and Doliage’s version ofTobradex (tobramycine/dexamethasone) were also listed. G

    BIOLOGICAL DRUGS

    Pfenex sees date slidefor its US teriparatidePfenex has pushed back by a quarter its earliest anticipated USlaunch date for its PF708 rival to Forteo (teriparatide), to the end of2019. “We believe we are on track to submit the 505(b)(2) new drugapplication (NDA) for PF708 to the US Food and DrugAdministration(FDA) in the fourth quarter of 2018, which, if approved, could allowfor a potential commercial launch as early as the fourth quarter of 2019in the US,” said Pfenex chief executive officer Eef Schimmelpennink,noting that the osteoporosis drug was the company’s “major focus”.Previously Pfenex had targeted a launch in the third quarter of 2019(Generics bulletin, 31 August 2018, page 24).

    Noting that the FDA had been clear that a Phase III studywould be required for approval, Schimmelpennink said “we believewe are the only company that in the near-term will seek approvalof a recombinant-derived teriparatide, and we believe we are theonly company that has completed clinical studies to support itssubmission”. A “constructive pre-NDAmeeting” with the FDA in Julyhad suggested that “no additional clinical, non-clinical or toxicologicalstudies were needed”.

    Schimmelpennink noted that Pfenex was “working closely”with partner Alvogen – who will market PF708 in the US under acollaboration between the two firms (Generics bulletin, 15 June 2018,page 12) – adding that the Iceland-based company had “proved to be avaluable partner” in “offering us access to their team’s expertise”. G

    AUTOIMMUNE DISEASES TREATMENTS

    Momenta settles withAbbVie over HumiraAsixth global settlement enabling commercialisation of a biosimilarof AbbVie’s Humira (adalimumab) has brought the latest dateannounced thus far for US market entry, continuing the previous trend.

    Momenta Pharmaceuticals’ agreement with the originator providesfor US market entry for the firm’s M923 biosimilar adalimumabproduct on 20 November 2023, subject to approval by the US Foodand Drug Administration (FDA). A filing with the US regulator isplotted by the end of this year. The US-based player may also, under thesettlement agreement, launch in the European Union (EU) immediatelyupon approval by the European Medicines Agency (EMA), with afiling planned in the first half of 2019.

    AbbVie says that it will grant Momenta a non-exclusive licenseon specified dates to its Humira intellectual property in the US and invarious other countries around the world. Momenta, in turn, will payroyalties toAbbVie, which underlined that it would make no paymentsto Momenta. Financial terms of the settlement were not revealed.

    Amgen, Samsung Bioepis, Mylan, Sandoz and Fresenius Kabi –in that order chronologically – have all previously settled withAbbVieon Humira, providing US biosimilar entry dates. These begin on 31January 2023, for Amgen’s FDA-approved Amgevita, and stretchthrough to Kabi’s and Sandoz’ biosimilars on 30 September.

    In the EU, themarket for biosimilar Humira formed on 16Octoberwith Amgen, Mylan, Samsung and Sandoz launching simultaneously.

    “There are significant manufacturing expenses ahead to enable usto market this product candidate,” CraigWheeler, Momenta’s presidentand chief executive officer, said during the firm’s third quarter earningscall, “and we believe bringing a commercial partner onboard in thenear-term could meaningfully reduce our share of these expenses.”

    M923 is one of two biosimilars registered in Momenta’s pipeline,following a proposed rationalisation announced last month (Genericsbulletin, 5 October 2018, page 3). Five of six biosimilars previouslybeing developed with Mylan are intended to be axed with the firms’M710 Eylea (aflibercept) candidate spared from the cull. “There areongoing discussions with Mylan,” Wheeler revealed.

    Momenta also provided an update on its separate rationalisationscheme to reduce its workforce by “approximately 50%”, with theloss of 110 jobs in total across the company. By 5 October, 37% of theworkforce had been axed, the company said, “with an additional 13%reduction planned over the next two to 12 months”. G

    Gen 16-11-18 Pgs.1-16.indd 13 14/11/2018 16:49

  • 14 bulletin 16 November 2018

    PRODUCT NEWSHIV DRUGS

    Sandoz is rocked byDutch ‘status quo’Sandoz has been stopped at the last minute from launching itsgeneric rival to Janssen’s Prezista (darunavir) HIV treatment in theNetherlands after the originator’s licensing partner, Pfizer’s GD Searle,persuaded a district court in The Hague to maintain the status quo bygranting an injunction.

    Court documents show that Sandoz on 18 October this year,“without any prior notification”, obtained a listing for its darunavirgeneric on the Netherlands’ G-Standaard database of drug prices.“Furthermore,” the court noted in granting the injunction, “Sandoz hasalready offered its product to wholesalers and intends to place it ontothe market on 1 November.”

    Responding on 1 November to Searle’s petition for a preliminaryinjunction on the grounds of infringing its supplementary protectioncertificate (SPC) 300283, which expires on 23 February 2019, theHague court recognised that Sandoz had agreed during a hearing tohold off its launch plans for “one week”, but not until a full ruling onthe merits of the case was delivered.

    Thus, the court needed to decide whether to grant the originator’smotion for an injunction.

    “Searle’s request is by no means without reason and it hasconsiderable interests in maintaining the status quo,” the court stated.In particular, the court was convinced by the originator’s fears ofa “price decay” for Prezista if Sandoz were allowed to introduce“at risk” its generic darunavir, stressing that this case differed fromsituations where the generic had already been in the market for sometime and the alleged infringer had a substantial interest in maintainingthe status quo.

    Referenced English rulingIn weighing the balance of interests of each party, the Hague

    court referenced a parallel Prezista SPC ruling by English High CourtJudge Richard Arnold in which he denied Sandoz’ argument that thelocal SPC was invalid because darunavir was specified or identifiedin the claims of the patent to which the SPC referred, European patentEP0,810,209 that Searle licenses to Janssen (Generics bulletin, 12May 2017, page 15).

    Sandoz had argued in the English case that the breadth of claim 1of the European patent EP0,810,209, to which the SPC referred, was sovast that a skilled person could not realistically produce all the coveredcompounds, nor could all the compounds plausibly be efficacious asprotease inhibitors.

    But Arnold ruled there was not “any tenable interpretation”of Article 3(a) of the EU’s SPC Regulation 469/2009/EC wherebydarunavir was not protected by the ‘209 patent.

    And while Sandoz had subsequently convinced the UK Court ofAppeal to refer to the Court of Justice of the European Union (CJEU)questions around the precise meaning of “the product is protectedby a basic patent in force”, as described in Article 3(a) of the SPCRegulation (Generics bulletin, 2 February 2018, page 15), the Haguecourt pointed out that neither the Court of Appeal nor the CJEU haddelivered a verdict in Sandoz’ favour.

    As a result, the Hague district court forbade Sandoz from offering,marketing and supplying its generic darunavir and set a penalty of50,000 (US$56,715) per violation of the prohibition. The courtalso ordered that its form of the antiretroviral be removed from theG-Standaard list as soon as possible. Gn [email protected]

    CIPLA has received final approval from the US Food and DrugAdministration (FDA) for its AB-rated generic version of Roche’s

    c e ncic ir 450mg tablets. The Indian firm said thedrug “is available for shipping immediately”.

    SANDOZ is voluntarily recalling one lot of s r n ssir c r i i e 100mg/25mg tablets at the consumer level

    in the US. The company said this was due to the trace amountof an impurity, N-nitrosodiethylamine (NDEA) contained in theactive pharmaceutical ingredient (API) losartan, manufactured byhejiang Huahai. Noting that its losartan tablets were produced by

    its Slovenian Lek subsidiary, Sandoz stressed that to date it had “notreceived any reports of adverse events related to this lot”. Separately,Aurobindo is voluntarily recalling 22 batches of ir es r n itsupplied to ScieGen Pharmaceuticals, also due to the detection ofNDEA in the API.

    ONCOBIOLOGICS has begun dosing patients in its first clinicaltrial for ONS-5010, its e ci biosimilar candidate, inpatients with wet age-related macular degeneration (wet AMD). Thefirst clinical study is set outside the US and is designed to serve asthe first of two adequate and well controlled studies for wet AMD,while the US portion of the second study is scheduled to begin inearly 2019 upon the submission of an investigational new drug (IND)application. Oncobiologics noted the drug was not being developedunder the biosimilar drug-development pathway.

    LUPIN has obtained an establishment inspection report (EIR) fromthe US Food and Drug Administration (FDA) after the agencycompleted a pre-approval inspection (PAI) at the Indian firm’s localfacility in Nagpur, Maharashtra, for its en in s i extended-release 100mg capsules. An audit carried out at the oral-soliddosage manufacturing plant in September was concluded “withoutany observations”, Lupin noted. Furthermore, the company haslaunched in the US a generic rival to GlaxoSmithKline’s e r n

    ne oral suspension 750mg/5ml following FDAapproval.Lupin has also received US approval for its generic version ofGenzyme’s ec r ( erc ci er ) 4 g/2ml multi-dose vials.

    INNOVENT BIOLOGICS – a Chinese biopharmaceutical player– has had its IBI303 biosimilar ir ( i ) candidateaccepted for filing by the country’s regulator, the recently-renamedNational Medical Products Administration (NMPA). “The new drugapplication(NDA)isbasedonanalytical,clinicalandpharmacokineticsdata generated from three clinical studies,” Innovent said of its NDA,the company’s second accepted by the NMPA. Phase III comparativeefficacy and safety studies were conducted in patients with ankylosingspondylitis. Michael u, Innovent’s head, said the company had “10products in clinical development, four in Phase III clinical trials.”

    CHUGAI has decided to withdraw its lawsuits and petitions forprovisional disposition order that were filed independently to theTokyo District Court against Daiichi Sankyo and Pfizer Japan,demanding the suspension of manufacturing and distributingbiosimilars of Genentech’s erce in ( r s ). Herceptinlicensee Chugai filed the lawsuit and petition in mid-October.

    FOAMIX PHARMACEUTICALS has announced top-line resultsfrom its Phase III program evaluating FM 103 in c c ine 1.5%foam, used to treat moderate-to-severe papulopustular rosacea. Twodouble-blind, randomised, vehicle-controlled studies – conducted ina total of 1,522 adults in the US – met both co-primary endpoints.The safety profile of FM 103 was “found to be favourable”. G

    IN BRIEF

    Gen 16-11-18 Pgs.1-16.indd 14 14/11/2018 16:49

  • 15bulletin16 November 2018

    PRODUCT NEWS

    AUTOMIMMUNE DISEASES TREATMENTS

    German funds selectImraldi due to priceDeep initial discounts of up to 40% versus AbbVie’s Humira(adalimumab) original have won Biogen’s Imraldi alternative anationwide supply contract with Germany’s GWQ group of healthinsurance funds.

    “With a discount of up to 40%, Biogen’s product offers by far thegreatest price advantage over the Humira original,” GWQ commentedas it claimed to have had Germany’s first nationwide contract forthe “particularly cost-effective adalimumab biosimilar” listed inpharmacy software.

    While Biogen set the pace by offering an Imraldi launch discountof just over 40% versus the list price for twoHumira pre-filled syringes(Generics bulletin, 2 November 2018, page 11), that advantage willdisappear once a price cut for Sandoz/Hexal’s Hyrimoz adalimumabbiosimilar enables it to match Imraldi from 15 November. The latestdata cited by the association of statutory health insurance doctorsfor Germany’s North Rhine region, the KVNO, shows that Amgen’sAmgevita will have a slightly higher price from 15 November, butwill still offer a discount of up to 38% versus Humira (see Figure 1).

    ‘Enormous savings’ expectedStressing that Europeanbiosimilars offered “absolutely comparable

    quality, safety and efficacy” versus their reference products, GWQsaid Imraldi’s lower price would release “enormous savings in thishighly prescribed therapeutic category”. Biogen Germany’s managingdirector,Wolfram Schmidt, said the company was delighted to continueits “proven collaboration” with the GWQ partner funds for Imraldi,the company’s third biosimilar anti-tumour necrosis factor (anti-TNF)alongside Benepali (etanercept) and Flixabi (infliximab). G

    RESPIRATORY DRUGS

    Hikma and Vecturaally on Ellipta rivalsHikma has announced a global development and marketingcollaboration deal with Vectura aimed at developing genericversions of GlaxoSmlithKline’s (GSK’s) Ellipta respiratory portfolio.The agreement on rivals to Ellipta – which builds on an existingcollaboration between the two firms to develop a generic version ofGSK’s Advair Diskus (fluticasone/salmeterol) – will use Vectura’sproprietary ‘open-inhale-close’ dry-powder inhaler device.

    According to Hikma, the deal “presents a significant opportunity,with net sales for Ellipta products in the US projected to be US$4 billionby 2024 and approximately US$5.5 billion globally”. GSK’s portfolioincludesBreoEllipta (fluticasone/vilanterol), TrelegyEllipta (fluticasone/umeclidinium/vilanterol), Relvar Ellipta (fluticasone/vilanterol), AnoroEllipta (umeclidinium/vilanterol) and Incruse Ellipta (umeclidinium).

    “The open-inhale-close dry powder inhaler programme includesthe development of AB-rated substitutable generics of up to fiveGSK respiratory medicines,” Hikma stated. “Hikma and Vectura haveagreed to develop and commercialise at least three of the portfolioproducts. A substitutable generic version of Breo Ellipta will beprioritised for the first wave of development,” Hikma noted, addingthat “pharmaceutical and device-development work has progressed inparallel with partnering discussions”.

    Hikma will make an upfront payment of US$15million to Vectura,which will fund and be responsible for initial device and formulationdevelopment. Meanwhile, Hikma will be responsible for clinicaldevelopment, regulatory submission and commercialisation.

    AUS$5 million milestone payment will be made by Hikma whenthe first product is transferred to Hikma for clinical manufacturing,with subsequent milestone payments of up to US$75 million due “atvarious stages of development”, including pharmacokinetic trials,clinical trials, abbreviated new drug application (ANDA) submissionsand US Food andDrugAdministration (FDA) approvals. On approval,Hikma will pay a profit share “up to a mid-teen percentage” for eachproduct, as well as sales milestones. In return, Vectura will contributeup to US$70 million towards Hikma’s development activities. Thiscontribution will be deferred and made through “a reduced profit-share mechanism following commercial launch of the first product”.

    “The generic respiratory market is a key area of pipeline focus forHikma,”observedSiggiOlafsson,Hikma’s chief executiveofficer. “Thisagreement leverages the investment we have made and the experiencewe have gained through our generic Advair Diskus programme.”

    Vectura chief executive JamesWard-Lilley said the deal “validatesVectura’s rare, industry-leading development capabilities” and reflects“our increased focus in our complex inhaled generic portfolio”.

    Hikma and Vectura’s US application for its VR315 rival toAdvairwas knocked back by the FDA earlier this year after the agencyrequested an additional clinical endpoint study (Generics bulletin, 16March 2018, page 1). The firms stated at the time that they anticipatedsubmitting new clinical data to the FDA“as early as possible in 2019”,with potential approval and launch in 2020.

    “Following interactions with the FDA,Vectura and Hikma believethe open-inhale-close dry powder inhaler device has the potential to bedeveloped as an AB-rated substitutable drug-device combination forgeneric versions of the GSK Ellipta portfolio,” Hikma stated. “Thenew device is an evolution of Vectura’s lever-operated multi-dosedevice and builds on Vectura and Hikma’s shared experience with thegeneric Advair Diskus programme.” Gn [email protected]

    Figure 1: List prices in Germany for packs of two and six adalimumab pre-filledsyringes as of 15 November (Source – KVNO)

    Brand Two-syringepack (€)

    Discount toHumira (%)

    Six-syringepack (€)

    Discount toHumira (%)

    Humira 1,911.47 – 5,324.49 –

    Amgevita 1,172.30 -38 3,420.27 -35

    Hyrimoz 1,144.65 -40 3,354.43 -37

    Imraldi 1,144.64 -40 3,354.43 -37

    HEPATITIS C DRUGS

    MPP gets new AbbVie licenceThe Medicines Patent Pool (MPP) has signed a new licence withAbbVie that the organisation says will “expand access to a keyhepatitis C treatment, glecaprevir/pibrentasvir”, a World HealthOrganization (WHO) recommended first-line treatment for peopleliving with the disease.

    The royalty-free licence for the oral once-daily combinationregimen “will enable quality-assured manufacturers to develop andsell generic medicines containing glecaprevir/pibrentasvir in 99 low-and middle-income countries (LMICs) and territories at affordableprices, enabling access to and treatment scale-up with the mosteffective pan-genotypic regimens”.

    MPPgovernanceboard chair,Marie-PauleKieny, saidglecaprevir/pibrentasvir was a “priority therapy for licensing for the MPP”. G

    Gen 16-11-18 Pgs.1-16.indd 15 15/11/2018 09:42

  • 16 bulletin 16 November 2018

    PEOPLE

    RESIGNATIONS

    Intellipharmaceutics seeks CFOIntellipharmaceutics has begun searching for a new chief financialofficer after n re ien announced plans to resign from 30November “to pursue another opportunity”.

    Patient “has agreed to continue to offer his services to the companythrough 31 December 2018, and is willing to continue thereafter on aconsulting basis at the company’s discretion”, the controlled-releaseoral-solids drug-delivery specialist noted.

    “The company has commenced a search to fill Patient’srole,” Intellipharmaceutics announced. “Pending the hiring of areplacement,” it indicated, “the functions of chief financial of