new drugs and pipeline news reviewed at the …...new drugs and pipeline news reviewed at the...

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Health NewsflashA Quarterly PublicationNew Drugs and Pipeline News Reviewed at the January to March 2019 DEC Meetings

The Drug Evaluation Committee (DEC) of Express Scripts Canada conducts monthly reviews of all new drugs receiving their Notice of Compliance from Health Canada, to ascertain their place in therapy and their possible impact on the private payer sector. The prices quoted in this document are approximations for general information purposes only, and are not intended, nor should they be relied upon, for purposes of any actual claims adjudication or reimbursement. This publication, describing new drugs of significance, is provided to our customers on a quarterly basis as a value-added service. We hope that you will find this Health Newsflash informative, timely, and useful.

NEW DRUGS

Belsomra™ (suvorexant)Dosage Form DIN & Strength Manufacturer AHFS Class

Tablet

02483505 – 5mg02483513 – 10mg02483521 – 15mg02483548 – 20mg

Merck Canada Inc.28:24.92 – Miscellaneous

Anxiolytics Sedatives and Hypnotics

Clinical Notes

Belsomra (suvorexant) is an orexin receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the orexin receptor suppresses wakefulness.

The approval of Belsomra was based on three clinical trials in patients with insomnia characterized by difficulties with sleep onset and sleep maintenance. Two similarly designed, 3-month, randomized, double-blind, placebo-controlled, parallel-group studies were conducted (Study 1 and Study 2). In both studies, non-elderly (age 18-64) and elderly (age ≥ 65) patients were randomized separately. In both studies non-elderly adults were treated with Belsomra 20 mg or placebo. Elderly patients were treated with Belsomra 15 mg or placebo. In Study 1 and Study 2, Belsomra 15 mg or 20 mg was superior to placebo for sleep latency as assessed both objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra 15 mg or 20 mg was also superior to placebo for sleep maintenance, as assessed both objectively by polysomnography and subjectively by patient-estimated total sleep time. The effects of Belsomra at night 1 (objective) and week 1 (subjective) were generally consistent with later time points.

In a 1-month crossover study (Study 3), non-elderly adults (age 18-64 years, mean age 44 years) were treated with placebo and Belsomra at a dose of 10 mg, 20 mg, 40mg, or 80 mg. Belsomra 10 mg and 20 mg were superior to placebo for sleep latency and sleep maintenance, as assessed objectively by polysomnography.

Indication(s)

For the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

Dose

The recommended initial dose is 10mg, taken no more than once per night and within 30 minutes of going to bed, with at least 7 hours remaining before the planned time of awakening. If the 10mg dose is well-tolerated but not effective, the dose can be increased. The maximum recommended dose is 20mg once daily.

Therapeutic Alternatives

Ativan (lorazepam)*, Restoril (temazepam)*, Sublinox (zolpidem)*, Imovane (zopiclone)*, Silenor (doxepin)

*generics available

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Place in Therapy

Belsomra appears to be a therapeutic alternative to other available sedative-hypnotic insomnia treatments. Belsomra is contraindicated in narcolepsy, and also has a warning regarding sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms.

Pricing

N/A

Impact

Insufficient information.

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Brineura™ (cerliponase alfa)Dosage Form DIN & Strength Manufacturer AHFS Class

IntracerebroventricularInfusion

02484013 – 150mg/5ml Biomarin International Ltd. 44:00.00 – Enzymes

Indication(s)

For the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency or Batten disease.

Dose

The safety and efficacy of Brineura in children less than 3 years of age has not been established. Limited data are available for children aged 2 years and no clinical trial data is available in children below 2 years of age.

The recommended dose in patients 2 years of age and older is 300 mg cerliponase alfa (10 mL solution) administered once every other week by intracerebroventricular (ICV) infusion. Brineura is administered into the cerebrospinal fluid (CSF) by infusion via a specific surgically implanted reservoir and catheter in the head.


None. Brineura is the first agent approved for the treatment of CLN2.

Clinical Notes

CLN2 is an extremely rare (0.5 to 1 case per 100,000 live births) type of lysosomal storage disorder that affects cells in the brain. Lysosomes are in every cell and contain enzymes that break down materials in the cell. One of these enzymes is called TPP1, which is missing or not working properly in children with CLN2 disease. Onset of CLN2 generally occurs between 2 and 3 years of age, with complete loss of ambulation by 6 years of age, progressive vision loss, and death between 6 and 16 years of age. Brineura helps to replace the missing TPP1 enzyme.

The efficacy of Brineura was evaluated in one Phase I/II, single-arm, open-label, multicenter pivotal study in patients ≥ 3 years of age with CLN2 disease and a Motor-Language CLN2 clinical rating scale (CRS) score ≥ 3. Children’s ability to walk and crawl as per the CLN2 clinical rating scale include the following: 3 (normal), 2 (some difficulty walking), 1 (needs help walking), and 0 (loss of walking/crawling abilities. All patients were treated with Brineura 300 mg once every other week via ICV infusion. In the pivotal study [n = 23], at Week 48, 87% of Brineura-treated patients (n = 20/23) were “responders” (i.e., experienced a < 2-point decline in the Motor-Language CLN2 CRS score). In a descriptive, non-randomized comparison, the mean decline was -0.4 units in Brineura-treated patients vs. -2.2 units in a natural history cohort of patients with CLN2 disease not treated with Brineura (n = 42). At Week 96, 63% of patients receiving Brineura (n = 14/22) continued to be considered “responders” based on Motor-Language CLN2 CRS scores.

Warnings and precautions with Brineura include ICV access device-related complications, cardiovascular adverse events, and hypersensitivity reactions.

Place in Therapy

Brineura is an enzyme replacement therapy approved for the treatment of CLN2, an ultra-rare, fatal, pediatric neurodegenerative disease. Data are limited to one very small, unpublished, single-arm trial in which Brineura reduced disease progression in the majority of treated patients over a 48-week study period. There is currently no survival data available. Brineura is administered into the CSF via an ICV access device and, therefore, carries some unique safety concerns.

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There are no other agents to prevent, stop, or reverse progression of CLN2 disease. Current therapy includes symptomatic management, prevention and treatment of complications, and palliative measures to preserve quality of life. The long-term effectiveness of this drug has not been determined.

Pricing

N/A

Impact


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Cresemba™ (isavuconazole)Dosage Form DIN & Strength Manufacturer AHFS Class

Intravenous injection; Capsule02483998 – 200mg/vial02483971 – 100mg capsule

AVIR Pharma 08:14.08 – Azoles

Dosage Form Loading Dose Maintenance Dose

100mg capsules 2 capsules every 8 hours for 6 doses (48 hours) 2 capsules once daily

200mg/vial1 reconstituted and diluted vial intravenously every 8 hours for 6 doses (48 hours)

1 reconstituted and diluted vial intravenously once daily


Vfend (voriconazole) and Fungizone/Ambisome (amphotericin B)

Clinical Notes

Invasive aspergillosis is an uncommon, but serious fungal infection that can be life-threatening. Invasive aspergillosis usually occurs in individuals with other underlying medical conditions (e.g., patients who have received a stem cell or solid organ transplant, patients taking high-dose corticosteroids or other immunosuppressive therapies).

Invasive mucormycosis is a rare, but very aggressive fungal infection. Immunosuppressed patients are at increased risk of developing invasive mucormycosis. The overall mortality rate is over 50% and it approaches 100% in patients with disseminated disease or those with persistent neutropenia.

The efficacy of Cresemba was established in two pivotal studies. SECURE was a randomized, double-blind, non-inferiority study comparing Cresemba with voriconazole for the primary treatment of invasive aspergillosis (n = 516). Patients in both the Cresemba and voriconazole groups were initially treated with IV therapy and then transitioned to oral therapy. Cresemba was non-inferior to voriconazole in the primary endpoint, all-cause mortality through Day 42, in the intent-to-treat (ITT) population (n = 516): 18.6% vs. 20.2%, respectively. Cresemba was non-inferior to voriconazole in the overall success rate (complete or partial response) at the end of treatment in the modified intent-to-treat (mITT) population (n = 272): 35.0% vs. 36.4%, respectively.

VITAL was an open-label, non-comparative study to evaluate the efficacy of Cresemba in patients with invasive mucormycosis (n = 37). Patients were treated with either oral or IV Cresemba. Efficacy measures were evaluated at the end of treatment (up to 180 days). At the end of treatment, 31.4% of patients had a successful overall response.

Indication(s)

Cresemba is an azole antifungal indicated for use in adults for the treatment of:

• Invasive aspergillosis; • Invasive mucormycosis.

Dose

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All-cause mortality through Day 42 was 37.8%. The most frequently reported AEs were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver function tests [LFTs] (16%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%). In total, 14% of patients permanently discontinued Cresemba treatment due to an adverse event; most commonly: confusional state, acute renal failure, increased blood bilirubin, convulsion, dyspnea, epilepsy, respiratory failure, and vomiting.

Place in Therapy

Invasive Aspergillosis: The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) recommend voriconazole as the drug of choice for the primary treatment of invasive aspergillosis. Both the oral and IV formulations of voriconazole can be used. The lipid formulations of amphotericin B may be considered as alternative primary therapy for some patients. Salvage therapy options include: lipid formulations of amphotericin B, oral posaconazole, oral itraconazole, caspofungin IV, and micafungin IV.

Invasive Mucormycosis: The American Thoracic Society (ATS) recommends conventional amphotericin B and the lipid formulations of amphotericin B as the drugs of choice. Oral posaconazole is recommended for patients who are intolerant of, or refractory to, amphotericin B.

Pricing

N/A

Impact


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Crysvita™ (burosumab)Dosage Form DIN & Strength Manufacturer AHFS Class

Subcutaneous injection02483629 – 10mg/ml02483637 – 20mg/ml02483645 – 30mg/ml

Kyowa Kirin Ltd. 08:18.24 – Monoclonal Antibodies

Indication(s)

Crysvita (burosumab Injection) is indicated for the treatment of X-linked hypophosphataemia (XLH) in adult and pediatric patients one-year of age and older.

Treatment should be initiated and monitored by a health professional experienced in the management of patients with metabolic bone diseases.

Dose

Pediatric Patients with X-linked Hypophosphataemia (1 to less than 18 years of age):

The recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.

Adult Patients with X-linked Hypophosphataemia (18 years of age and older):

The recommended dose regimen in adults is 1 mg/kg of body weight, rounded to the nearest 10 mg up to a maximum dose of 90 mg, administered every four weeks.

Dose recalculation should be performed if there are changes in patient weight of ±10%.

Crysvita is administered by subcutaneous (SC) injection and should be administered by a health professional.


None available. Symptomatic treatment with phosphate salts and calcitriol (Rocaltrol) have been used in the past; however, these therapies have a high risk of adverse events (e.g., kidney stones) and generally have sub-optimal outcomes (moderate increase in serum phosphorous levels but little impact on skeletal abnormalities).

Clinical Notes

X-linked hypophosphataemia (XLH) is a rare metabolic bone disease with significant clinical consequences in both children and adults, due largely to fibroblast growth factor 23 (FGF23) excess, which results in chronic low blood phosphorus levels. XLH affects an estimated 1:20-25,000 persons. XLH usually presents in early childhood as manifestations of rickets, usually as the child engages in weight bearing activities between the ages of one and two years. These are seen as bowing of the long leg bones, abnormalities in skull shape, and sometimes bone pain. Gross motor milestones are often delayed.

The efficacy of Crysvita was established in four pivotal trials, including two open-label, 64-week studies in pediatric patients, one double-blind, 24-week study in adult patients, and one single-arm 48-week study in adult patients with XLH.

• In Study 201 [n = 52], Crysvita SC (both every two weeks [Q2W] and every four weeks [Q4W] dosing) increased mean serum phosphorus levels in patients 5 to 12 years of age with XLH (mean 2.33 mg/dL at baseline to 3.16 mg/dL at Week 64; P < 0.001).

- Radiographic improvements were also observed. Crysvita improved the mean Thacher Rickets Severity Score (RSS) 44% to 58% from baseline to Week 64. Radiographic Global Impression of Change (RGI-C) scores also indicated healing from baseline (+1.62 and +1.53 at Week 64 with Crysvita Q2W and Q4W, respectively [P < 0.0001]).

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• In Study 205 [n = 13], Crysvita SC Q2W increased mean serum phosphorus from 2.5 mg/dL (baseline) to 3.5 mg/dL at Week 40 (interim analysis) in patients 1 to 4 years of age. Normal serum phosphorus (for age) was observed in 77% of patients at Week 40.

- Additionally, the mean RSS was reduced by 59% from baseline to Week 40 and at Week 40 all patients had an RGI-C score ≥ +2.0 (indicative of substantial healing).

• Study 303 [n = 134], a double-blind, placebo-controlled, multicenter, 24-week, Phase III study randomized adults with XLH to Crysvita 1 mg/kg SC or placebo Q4W.

- Significantly more patients achieved a mean serum phosphorus level > 2.5 mg/dL with Crysvita (94.1%) compared with placebo (7.6%) over the 24-week treatment period.

- Additionally, significantly more active baseline fractures/pseudofractures were healed with Crysvita (43%) compared with placebo (8%).

• Study 304 [n=14], an open-label, single-arm, 48-week, Phase III study assessed the effects of Crysvita on improvement of osteomalacia in adults with XLH. They received Crysvita 1mg/kg SC Q4W.

- Histomorphometric improvement in osteomalacia was observed in ten patients as demonstrated by decreases in proxy measure.

- Osteoid volume/Bone volume (OV/BV) changed from a mean (SD) score of 26.1% (12.4) at baseline to 11.2% (6.5), a reduction of 57% (n=11). Osteoid thickness (O.Th) declined from a mean (SD) of 17.2 (4.1) micrometers to 11.6 (3.1) micrometers, a reduction of 33% (n=11). Mineralization lag time (MLt) declined from a mean (SD) of 594 (675) days to 156 (77) days, a reduction of 74% (n=6).

The most common adverse effects, with reported incidence of 20% or higher, in children were headache, injection site reactions, vomiting, fever, pain in the extremities, low serum vitamin D, rash and toothache. Adults experienced these along with back pain and restless leg syndrome.

Place in Therapy

Based on the natural course of XLH, Crysvita would be considered the drug of choice for the treatment of pediatric patients with XLH. The initiation of the use of the drug in adult patients is less clear since much of the individual’s skeletal development has already taken place. The impact of Crysvita on long-term fracture prevention and pain reduction in adults has not been established.

Pricing

Annual cost: $139,000 - $1,200,000

Impact

High impact. Although utilization is expected to be low (XLH is a rare disease) cost per claimant is high.

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Demylocan™ (decitabine)Dosage Form DIN & Strength Manufacturer AHFS Class

Intravenous injection 02484811 – 50mg/vial Pendopharm Inc. 10:00.00 – Antineoplastic Agents

Indication(s)

Demylocan is indicated for the treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System (IPSS) groups.

Dose

There are two regimens for Demylocan administration. For either regimen, it is recommended that patients be treated for a minimum of 4 cycles unless unacceptable toxicity occurs after dose delays/adjustments or standard supportive care. Treatment should be continued as long as the patient continues to benefit or until disease progression.

Regimen 1: 15 mg/m2 IV (over 3 hours) repeated every 8 hours for 3 days. The cycle should be repeated every 6 weeks.

Regimen 2: 20 mg/m2 IV (over an hour) repeated daily for 5 days. The cycle should be repeated every 4 weeks.


Vidaza and generics (azacitidine – reserved for Intermediate-2 and High-Risk MDS)

Gleevec and generics (imatinib – indicated for MDS associated with platelet-derived growth factor receptor gene re-arrangement)

Revlimid (lenalidomide – indicated for transfusion-dependent anemia due to Low- or Intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with/without additional cytogenetic abnormalities)

Clinical Notes

Myelodysplastic syndromes (MDS) are a group of cancers that affect blood cells in the bloodstream and bone marrow. MDS starts in the blood stem cells of the bone marrow; there are changes in genes that cause abnormalities and impact the production of blood cells (red blood cells, white blood cells, platelets). Blood cells are either abnormal and defective or their number is decreased. Sometimes, they crowed the bone marrow or die as soon as they leave it, decreasing even more the number of viable blood cells available and deteriorating the cell production capacity of the bone marrow. There are many subtypes of MDS, classified depending upon the type and number of low blood cell counts, types of blood cells in the bone marrow that are abnormal, number of blast cells found in the blood and bone marrow, types of chromosome changes seen and the presence of red blood cells that have too much iron (ring sideroblasts). MDS may continue to get worse over time and in one third of patients, it can progress to a fast-growing and aggressive cancer called acute myeloid leukemia (AML).

Decitabine is believed to exert its antineoplastic effects by hypomethylation of DNA. It inhibits DNA methylation at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation.

Efficacy and safety of decitabine was demonstrated in two clinical trials: Study D-0007 and ADOPT.

Study D-0007 was a randomized Phase III trial conducted in 170 subjects with MDS. They were randomized to receive either intravenous decitabine (15 mg/m2 over a 3-hour period, every 8 hour, for 3 consecutive days) plus supportive care (SC) or SC alone. SC consisted of blood and/or blood products transfusions, prophylactic antibiotics and hematopoietic growth factors. The co-primary endpoints were overall response rate (partial and complete response) and time to acute myeloid leukemia (AML) or death. The overall response rate in the decitabine+SC arm was 17% versus 0% in the SC arm, with a median duration of response in responders of 288 days. However, decitabine did not significantly delay time to AML or death.

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The ADOPT trial was a single-arm study conducted in 99 patients with any French-American-British MDS subtype and IPSS Intermediate-1, Intermediate-2 or High-Risk prognostic scores. Patients received decitabine 20 mg/m2 by intravenous infusion over one-hour daily, on day 1-5 of week 1 every 4 weeks. Primary endpoint was overall response rate (partial and complete response). Overall response rate was 16%, with 15 patients achieving complete response and one patient only responding partially. The median duration of response was 443 days.

Place in Therapy

Decitabine is an additional treatment option for MDS, a family of rare blood cancers. As it is indicated for more subtypes of MDS compared to already available alternatives, it constitutes an interesting therapy for patients even though the only randomized clinical trial did not demonstrate a significant delayed time to death or acute myeloid leukemia.

Pricing

N/A

Impact


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Indication(s)

Idhifa™ (enasidenib tablets) is indicated for the treatment of adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. [NOC/c]

Treatment with Idhifa should be initiated following confirmation of IDH2 mutation through a validated test.

Dose

The recommended dose of Idhifa is 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity. It is recommended to treat patients for a minimum of 6 months to allow time for clinical response. Dosage reductions may be required due to toxicity and should be as directed in the product monograph.


Idhifa is the only targeted therapy for individuals with IDH2 mutations.

Idhifa™ (enasidenib)Dosage Form DIN & Strength Manufacturer AHFS Class

Tablet02485427 – 50mg02485435 – 100mg

Celgene Inc. 10:00.00 – Antineoplastic Agents

Clinical Notes

Acute myeloid leukemia (acute myelogenous leukemia, AML) is a malignant disorder of immature hematopoietic cells, characterized by inhibition of differentiation and rapid proliferation of abnormal myeloid precursors. These abnormal cells accumulate in the bone marrow and interfere with the production of normal blood cells.

The most recent incidence and mortality statistics for acute myelogenous leukemia in Canada are from 2013:

• 1,315 Canadians were diagnosed with acute myelogenous leukemia.

• 1,047 Canadians died from acute myelogenous leukemia.

• 740 men were diagnosed with acute myelogenous leukemia and 589 died from it.

• 575 women were diagnosed with acute myelogenous leukemia and 458 died from it.

Mutations of the IDH2 isoform are found in 8-19% of patients with AML. These mutations lead to the dysregulation of cellular metabolism and arrest of cell differentiation, which then leads to leukemic cell proliferation.

Idhifa blocks the activity of mutant IDH2 variants. By inhibiting the mutant IDH2 enzyme, Idhifa reduces blast counts, and increases the percentages of mature myeloid cells.

The efficacy of Idhifa was evaluated in one open-label, single-arm, multicenter, two-cohort, unpublished Phase I/II pivotal trial involving 199 adults with relapsed or refractory AML and IDH2 mutation. Patients had received a median of two prior therapies. The median follow-up was 6.6 months.

• Complete remission (CR) was achieved in 19% of patients. Complete remission with partial hematologic recovery (CRh) was noted in 4% of patients.

• For patients who achieved CR/CRh, the median time to first response was 1.9 months (range 0.5 to 7.5 months). The median time to best response for such patients was 3.7 months (range, 0.6 to 11.2 months).

• For patients achieving CR/CRh, the median duration of response (DOR) was 8.2 months.

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Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 34% of patients (n = 53/157) became independent of RBC and platelet transfusions. Continuous daily enasidenib treatment was generally well tolerated and induced hematologic responses in patients for whom prior AML therapy had failed. Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of Idhifa.

Place in Therapy

Idhifa is a targeted therapy for patients with relapsed or refractory AML who have the IDH2 mutation. Relapsed/refractory AML is complex and difficult to treat; chemotherapeutic and other modalities are limited for patients at this time. In addition, few options are available among those ineligible for intensive chemotherapy. Idhifa represents a unique agent for patients with relapsed or refractory AML who have the IDH2 mutation. Further studies, use in clinical practice, updated guidelines, and longer-term data will further define the role of Idhifa in AML management.

Pricing

Impact

High impact. Although low utilization is expected, drug cost very high.

Unit cost50mg Tablet 100mg Tablet

$1.22 $1.22

Monthly cost $36,500

Annual cost $438,000

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Indication(s)

Lorbrena (lorlatinib) is indicated as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib and alectinib. [NOC/c]

Dose

Recommended dose is 100 mg taken once daily orally. Treatment should be continued as long as the patient is deriving clinical benefit from therapy.


Avastin (bevacizumab, in combination with carboplatin/paclitaxel)

Off-label: Keytruda (pembrolizumab), Opdivo (nivolumab)

Lorbrena™ (lorlatinib)Dosage Form DIN & Strength Manufacturer AHFS Class

Tablet02485966 – 25 mg02485974 – 100 mg

Pfizer Canada Inc. 10:00.00 – Antineoplastic Agents

Clinical Notes

Lorbrena (lorlatinib) is a selective, adenosine triphosphate (ATP) competitive, brain-penetrant small molecule inhibitor of ALK and ROS/ tyrosine kinases that addresses mechanisms of resistance following treatment with ALK inhibitor therapy.

The safety and efficacy of Lorbrena was assessed in a single-arm clinical trial (B7461001) where a total of 197 patients with ALK-positive metastatic NSCLC, previously treated with one or more ALK TKIs were enrolled. 62% of patients had evidence of brain metastases. Patients received Lorbrena 100 mg once daily continuously. The primary efficacy endpoint in the Phase 2 portion of the study was objective response rate (ORR), including intracranial ORR. Secondary endpoints included: duration of response (DOR), intracranial DOR, time to tumor response (TTR) and progression-free survival (PFS). ORR was 47.2%, with 4 patients achieving complete response and 89 achieving a partial response. PFS was 7.4 months. Intracranial ORR was 53.0% and DOR was 14.5 months.

The most common adverse events (AEs) in patients treated with Lorbrena in the pivotal study (incidence ≥ 25%) were edema (57%), peripheral neuropathy (47%), cognitive effects (27%), dyspnea (27%), and fatigue (26%). Fatal AEs occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%).

Place in Therapy

Lorbrena is an additional alternative for the treatment of metastatic NSCLC, in a third-line setting. There are not many approved therapies for indications for a cancer as advanced, with only Avastin currently being approved by Health Canada.

Pricing

N/A

Impact


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Indication(s)

Onstryv is a monoamine oxidase type B (MAO-B) inhibitor that is indicated as an add-on therapy to a regimen that includes levodopa for the treatment of the signs and symptoms of idiopathic Parkinson’s disease (PD) in patients experiencing “off” episodes while on a stable dose of levodopa.

**Onstryv has not been shown to be effective as monotherapy for the treatment of PD**

Dose

The starting dose is 50 mg once per day. After 2 weeks the dose may be increased to 100 mg once per day.


Azilect (rasagiline)*; Eldepryl (selegiline)*†; Comtan (entecapone)*; Stalevo (levodopa-carbidopa/entacapone); Movapo (apomorphine HCl) subcutaneous injection

*generics available † brand discontinued

Onstryv® (safinamide mesylate)Dosage Form DIN & Strength Manufacturer AHFS Class

Tablet02484641 – 50 mg02484668 – 100mg

Valeo Pharma Inc. 28:36:32 – Monoamine Oxidase B Inhibitors

Clinical Notes

Patients with PD typically experience a smooth and even response to the early stages of levodopa treatment. As the disease advances, however, the effect of levodopa begins to wear off several hours after some or even all doses, leaving patients aware that the duration of action of a dose of levodopa is not being sustained. As many as 50 percent of patients on levodopa for several years will experience motor fluctuations and dyskinesia.

The main medical strategies for patients with PD who develop motor complications are (1) Adjusting the levodopa doses and dosing schedule and (2) Adding an additional antiparkinson medication, like Onstryv (an MAO-B inhibitor).

Safinamide is a highly selective and reversible inhibitor of monoamine oxidase B (MAO-B). By blocking catabolism of dopamine, inhibition of MAO-B (one of the main enzymes involved in the catabolic metabolism of levodopa) is thought to increase extracellular levels of dopamine in the striatum and subsequently increase dopaminergic activity.

The efficacy of Onstryv as an add-on therapy to a stable dose of levodopa, alone or in combination with other PD medications, was established in two pivotal, Phase III, randomised, double-blind, placebo-controlled, multi-centre clinical trials conducted over 26 weeks (Study 1 [N=669] and the SETTLE study [N=549]).

In both studies the primary efficacy endpoint was the mean change from baseline in total daily ON time without troublesome dyskinesia, based on 18-hour diaries completed by patients for at least 3 days before each scheduled assessment. ON time was defined as time when PD medication was providing benefit with regard to mobility, slowness and stiffness. ON time without troublesome dyskinesia was defined as ON time without dyskinesia plus ON time with non-troublesome dyskinesia.

Safinamide was effective as an adjunctive treatment with levodopa compared with placebo in these trials, safinamide increased mean daily "on" time without troublesome dyskinesia and improved motor function by approximately 1.4 hours, compared with 0.7 hours for placebo.

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Place in Therapy

Onstryv demonstrated efficacy as adjunctive treatment to levodopa in patients with PD experiencing “off” episodes and increased the mean daily “on” time by up to 1.4 hours compared with placebo in the pivotal trials which makes it a therapeutic alternative to other MAO-B inhibitors.

Therapeutic alternatives are used to reduce “off-time” or extend levodopa effectiveness. There are no oral alternatives for acute treatment of “off” episodes.

Comparative Pricing

Impact

Intermediate impact – shift from similar to lower cost alternatives.

Drug Estimated Annual Cost

Onstryv $2,500

Apo-Rasagiline $2,200

Teva-Seligiline $200 - $400

Apo-Entacapone Annual cost: $1,168 (at maximum dose)

Movapo Injection Annual cost: $7,740 (based on 48-hour stability)

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Indication(s)

Oxervate is indicated for the treatment of moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis in adults.

Dose

Instill one drop of Oxervate in the conjunctival sac of the affected eye(s), 6 times a day at intervals of 2 hours between drops, starting from the morning and within 12 hours. Treatment should be continued for eight weeks.


Artificial tears, surgical intervention

Oxervate™ (cenegermin)Dosage Form DIN & Strength Manufacturer AHFS Class

Ophthalmic solution 02485613 – 20 mcg/ml Dompé farmaceutici S.p.A. 52:92:00 – Miscellaneous EENT Drugs

Clinical Notes

Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by an impairment of corneal sensory innervation, characterized by decreased or absent corneal sensitivity resulting in epithelial keratopathy, ulceration, and perforation, it can progress to loss/impairment of vision and/or anatomical loss of the eye. Current treatment modalities (e.g., preservative-free artificial tears and ophthalmic antibiotics) are supportive therapies and do not accelerate corneal healing. Surgical intervention is only reserved for refractory cases.

Oxervate is a recombinant form of human nerve growth factor. Nerve growth factors play a role in supporting corneal innervation and integrity.

The efficacy and safety of Oxervate were evaluated in two multicenter, randomized, double-blinded, vehicle-controlled clinical studies (NGF0212 monolateral disease and NGF0214 bilateral disease) in adult patients with moderate (persistent epithelial defect) (PED) or severe (corneal ulcer) neurotrophic keratitis refractory to non-surgical treatments. In both studies, patients received Oxervate or vehicle six times daily in the affected eye(s) for eight weeks, and underwent a follow-up period.

The primary efficacy endpoint was the percentage of patients experiencing complete resolution of corneal staining, this was defined as no corneal fluorescein staining in the area of the PED or corneal ulcer and no persistent staining elsewhere in the cornea (i.e., 0 mm lesion size and no residual staining), as determined by a Central Reading Center, at the Week 4 and Week 8 visits. Significantly more patients receiving Oxervate achieved complete corneal healing compared to the vehicle arm (61.85% vs 22.6% respectively).

The key secondary efficacy endpoint was the percentage of patients achieving corneal healing, defined as the greatest diameter of <0.5 mm of the corneal fluorescein staining in the area of the PED or corneal ulcer (i.e., <0.5 mm lesion size), as determined by a Central Reading Center, at the Week 4 and Week 8 visits.

Oxervate treated patients demonstrated significant improvement compared to the vehicle arm (66.25% vs 33.65% respectively).

Place in Therapy

Oxervate is the first and only pharmacologic therapy approved for the treatment of neurotrophic keratitis. It has proven effective in treating patients with this condition. To date surgical intervention was the only treatment alternative. This is considered to be an invasive approach and while it is effective, the procedure may result in poor cosmetic outcomes (i.e., residual scar tissue, permanent eyelid fusion).

Pricing

N/A

Impact


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Indication(s)

Vizimpro (dacomitinib) is indicated for the first-line treatment of adult patient with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) with confirmed epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations. A validated test is required to identify EGFR mutation status.

Dose

The recommended dose is 45 mg taken orally once daily until disease progression or unacceptable toxicity occurs. Dose modifications may be required based on individual tolerability and safety.


EGFR TKIs: Tagrisso (osimertinib, 3rd generation); Iressa (gefitinib, 1st generation)*; Giotrif (afatinib, 2nd generation); Tarceva (erlotinib, 1st generation)*

*generics available

Vizimpro™ (dacomitinib)Dosage Form DIN & Strength Manufacturer AHFS Class

Tablet02486024 – 15 mg02486032 – 30 mg02486040 – 45 mg

Pfizer Canada Inc. 10:00.00 – Antineoplastic Agents

Clinical Notes

Vizimpro is a pan-human epidermal growth factor receptor (HER) (EGFR/HER1, HER2 and HER4) inhibitor, with clinical activity against mutated EGFR with deletions in exon 19 or the L858R substitution in exon 21. Unlike first generation EGFR TKIs (erlotinib, gefitinib), dacomitinib is a second generation TKI that binds selectively and irreversibly to all three HER family targets thereby providing prolonged inhibition.

The efficacy and safety of Vizimpro were demonstrated in the ARCHER 105 clinical trial conducted in patients with unresectable, locally advanced or metastatic NSCLC harboring activating mutations of EGFR (confirmed EGFR exon 19 deletion or 21 L858R substitution mutations by a standardized and commercialized test). Patients were randomized to receive either Vizimpro 45 mg once daily or gefitinib (Iressa) 250 mg once daily until disease progression/unacceptable toxicity. The primary endpoint was progression-free survival (PFS), other efficacy endpoints included objective response rate (ORR), duration of response (DoR) and overall survival (OS). Tumor assessments were conducted every 8 weeks.

Vizimpro demonstrated a statistically significant and clinically meaningful improvement in PFS compared to gefitinib (14.7 months versus 9.2 months). Overall survival analysis showed a hazard ratio of 0.760 and a gain of 7.3 months in OS for Vizimpro.

The most common adverse events (AEs) in patients treated with Vizimpro in the pivotal studies (incidence ≥ 20%) were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). Serious AEs occurred in 27% of patients treated with Vizimpro and the most common serious AEs were diarrhea (2.2%) and interstitial lung disease (ILD) [1.3%]. AEs leading to permanent discontinuation of Vizimpro occurred in 18% of patients, primarily due to rash (2.6%), ILD (1.8%), stomatitis (0.9%), and diarrhea (0.9%). Compared with other EGFR-TKIs, the incidence and severity of AEs were higher with Vizimpro.

Place in Therapy

Vizimpro is another treatment option available for the treatment of EGFR mutated NSCLC in an already crowded pharmacological area. It has been proven superior in terms of progression-free survival, duration of response and time to treatment failure compared to a first-generation TKIs.

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Comparative Pricing

Impact

Intermediate impact – potential cost-shift from lower priced alternatives.


Vizimpro $43,000

Apo-Gefitinib $23,000

Teva-Erlotinib $26,000

Tagrisso $108,000

Giotrif $27,000

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Indication(s)

Vyzulta (latanoprostene bunod ophthalmic solution, 0.024%) is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Dose

The recommended dosage is one drop in the conjunctival sac of the affected eye(s) once daily in the evening.


Xalatan (latanoprost)*; Lumigan/Lumigan RC (bimatoprost)*; Travatan Z/Izba (travoprost)*; Xalacom (latanoprost/timolol)*; DuoTrav PQ (travoprost/timolol)

*generics available

Vyzulta™ (latanoprostene bunod)Dosage Form DIN & Strength Manufacturer AHFS Class

Ophthalmic solution 02484218 – 0.024% Bausch & Lomb Inc. 52:40.28 – Prostaglandin Analogs

Clinical Notes

Vyzulta (latanoprostene bunod) ophthalmic solution 0.024% is a nitric oxide (NO)-donating prostaglandin F2a analogue approved for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension. It is thought to lower IOP by increasing aqueous humour outflow through the uveoscleral pathway (mediated by latanoprost acid) and increasing aqueous humour outflow through the trabecular meshwork pathway (mediated by NO).

The efficacy of Vyzulta was evaluated in two non-inferiority pivotal studies: APOLLO and LUNAR.

• In the APOLLO study [n = 420], the mean IOP in the study eye was significantly lower in the Vyzulta arm compared with timolol 0.5% arm (range of 17.8 to 18.7 mmHg in the Vyzulta arm vs. 19.1 to 19.8 mmHg in the timolol 0.5% arm) at all efficacy time points (up to 3 months); non-inferiority of Vyzulta to timolol 0.5% was demonstrated.

• In the LUNAR study [n = 420], the mean IOP in the study eye was significantly lower in the Vyzulta arm compared with timolol 0.5% arm (range of 17.7 to 19.2 mmHg in the Vyzulta arm vs. 18.8 to 19.6 mmHg in the timolol 0.5% arm) at the majority of time points measured (up to 3 months); non-inferiority of Vyzulta to timolol 0.5% was demonstrated.

Glaucoma is a clinical term referring to a variety of conditions with the common feature of an optic neuropathy (i.e., glaucomatous optic neuropathy [GON]) characterized by a distinctive loss of retinal nerve fibres and optic disc changes. Loss of this neural tissue can lead to an irreversible loss of visual field (VF), usually beginning paracentrally, but becoming complete if the disease is unchecked. GON can develop under a number of circumstances with varying contributions by several known and as yet unidentified risk factors. The clinical term glaucoma is sometimes used when one risk factor, elevated intraocular pressure (IOP), is extreme and GON is impending, but not yet present (i.e., acute glaucoma).

Place in Therapy

Vyzulta is a modification of the prostaglantin analogue, latanoprost, which potentially provides an additional mechanism of action: nitric oxide-mediated relaxation of the trabecular meshwork/Schlemm’s canal. The duo-mechanism allows for aqueous humour outflow through both the trabecular meshwork and the uveoscleral pathway (the typical prostaglandin analogue mechanism).

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Pricing

Impact

Intermediate impact. Higher cost than available generics but potentially more efficacious (no direct data available).


Vizulta $110

Sandoz-Latanoprost $45

SDZ-Latanoprost / Timolol $51

DuoTrav PQ $115

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Indication(s)

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Dose

Yescarta is provided as a single-dose, one-time treatment in a patient-specific infusion bag. Each single infusion bag of Yescarta contains a suspension of anti-CD19 chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The target dose is 2 x 106 CAR-positive viable T cells per kg body weight (range: 1 x 106 – 2.4 x 106 cells/kg), with a maximum of 2 x 108 CAR-positive viable T cells for patients 100 kg and above.

Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on the fifth, fourth and third day before Yescarta infusion.

Premedication with acetaminophen and diphenhydramine is recommended 1 hour before infusion. Avoid prophylactic systemic corticosteroids as they may interfere with the activity of Yescarta. Ensure that Actemra® (tocilizumab injection for IV use) is available for the management of cytokine release syndrome (CRS).


Kymriah (tisagenlecleucel-T)

Allogenic hematopoietic cell transplantation (HCT)

Yescarta™ (axicabtagene ciloleucel)Dosage Form DIN & Strength Manufacturer AHFS Class

Intravenous injection02485648 – maximum of 200,000,000 anti-CD19

CAR T CellsGilead Sciences Canada Inc. 10:00.00 – Antineoplastic Agents

Clinical Notes

Aggressive B-cell lymphoma is a subtype of B-cell non-Hodgkin’s lymphomas (NHLs) that encompasses a clinically and molecularly heterogeneous group. In this group, diffuse large B-cell lymphoma (DLBCL) is the most common with ~22,000 cases a year in the US and it represents 30%–35% of all lymphomas. Within DLBCL itself, there is additional heterogeneity and this is reflected in the World Health Organization 2016 classification that lists further subtypes of DLBCL to include high-risk histologies such as high-grade B-cell lymphomas not otherwise specified (NOS) and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, known as double (DHL) or triple hit lymphomas (THL). Primary mediastinal B-cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL) are less frequent, but important variant subtypes that are also described.

One mechanism by which the immune system is able to recognize and fight cancer cells is through activation of T-lymphocytes that use T-cell receptors to recognize tumor peptides presented on major histocompatibility complexes. Once the T cells are activated, proliferation of T cells and cytotoxic granule secretion ensues, which leads to antitumor activity and lysis of tumor cells. However, tumors perform immune evasion by several mechanisms including increased expression of immune checkpoints (that limit T-cell activation and cause T-cell exhaustion) and effects of the tumor microenvironment. The design of CAR T cells is intended to enhance T-cell responses against tumor cells.

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Yescarta is a cell-based gene therapy that combines three innovative technologies: cellular therapy, gene therapy, and immunotherapy. Each Yescarta dose is customized and created using an individual patient’s lymphocytes which are obtained by a standard leukapheresis procedure. The patient’s T cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein, a chimeric antigen receptor (CAR) that directs the T cells to recognize and eliminate the leukemic cells that contain a specific surface antigen (CD19). After modification and expansion, the cells are infused back into the patient to destroy the cancer cells. Patients receive lymphocyte-depleting chemotherapy before the Yescarta infusion. Of note, patients undergo a waiting period when the cell product is prepared for administration (approximately 3 to 4 weeks) at a specialized facility. Upon reintroduction of the modified T cells into the patient, CAR T engagement of CD19-expressing cancer cells results in T-cell activation, proliferation and secretion of inflammatory cytokines and chemokines resulting in tumor cell lysis.

The efficacy of Yescarta was established in one single-arm, open-label, Phase II, multicenter trial that included adult patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), ZUMA-1. Yescarta was given as a single infusion after lymphocyte-depleting chemotherapy. In total, 101 of 111 patients who underwent leukapheresis received Yescarta and most (76%) had DLBCL, 16% of patients had transformed follicular lymphoma, and 8% of patients had primary mediastinal large B-cell lymphoma. The median number of prior therapies was three. The median dose was 2.0 x 106 CAR-positive viable T cells.

• At a median follow-up of approximately 8 months, the objective response rate was 72% (n = 73/101). The complete remission rate was 51% and the partial remission rate was 21%.

• The published data report that at a median follow-up of 15.4 months 42% of patients continued to have a response. The overall survival rate at 18 months was 52%.

A black box warning is in place on the product monograph for two key serious, potentially fatal, adverse effects.

Cytokine release syndrome (CRS): Yescarta therapy has led to CRS, which has been fatal or life-threatening. In the pivotal study, CRS of any grade occurred in 94% of patients (n = 101/108) receiving Yescarta; 13% of patients (n = 14/108) had ≥ Grade 3 CRS. The median time to onset was 2 days (range, 1 to 12 days) and the median duration of CRS was 7 days (range, 2 to 58 days). Before infusion of Yescarta, ensure that two doses of Actemra (tocilizumab) are available.

Neurologic toxicities: After treatment with Yescarta, neurologic toxicities were observed in 87% of patients, some of which were fatal or life-threatening, also known as CAR-T Related Encephalopathy Syndrome (CRES). CRES is related to CRS. Most of the neurologic toxicities (98%) were reported within the first 8 weeks of Yescarta infusion, with a median time to onset of 4 days (range, 1 to 43 days). The median duration of neurologic toxicities was 17 days. Neurologic toxicities ≥ Grade 3 occurred in 31% of patients.

Place in Therapy

Yescarta is the second CD19-directed genetically-modified autologous T cell immunotherapy that employs an innovative new technology. Relapsed or refractory DLBCL and related conditions have a paucity of highly-effective therapies. Yescarta therapy led to a very good objective response rate and a complete remission rate. Responses appear durable, although a longer duration of follow-up is desired. Long-term follow-up, additional published data, and clinical experience will further define Yescarta’s place in therapy.

Pricing

N/A

Impact

Administration of this drug requires highly specialized facilities (e.g., hospitals that conduct stem cell transplants) and is not expected to impact private plans.

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Generic Name Reference Drug(Brand)

Rank by ingredient cost in 2018 Manufacturer Route of

AdministrationApproved Indications/

Comments

acetaminophen Ofirmev 381 Avir Phama Inc. IntravenousManagement of acute pain and fever

arsenic trioxide Trisenox N/A Teva Canada Ltd. IntravenousInduction of remission and consolidation in patients with acute promyelocytic leukemia

budesonide Entocort 1038Tillots Pharma

GmbHCapsule

(controlled-release)Mild to moderate active Crohn's disease

dexmedetomidine Precedex N/A Auro Pharma Inc. IntravenousFor sedation of non-intubated patients prior to or during surgical procedures

fulvestrant Faslodex 425 Teva Canada Ltd. IntramuscularAdvanced or metastatic breast cancer

itraconazole Sporanox 515 Jamp Pharma Corp. Oral Solution

Treatment of oral and/or esophageal candidiasis in HIV-positive or other immunocompromised patients

methylphenidate hydrochloride

Biphentin 5Bard

Pharmaceuticals (1990) Inc.

Extended-Release Capsule

Treatment of ADHD in children (6-11 years of age), Adolescents (12-18 years of age), Adults (> 18 years of age)

mupirocin Bactroban Cream 490Glenmark

Pharmaceuticals Canada Inc.

Topical CreamInfected lesions such as lacerations, sutured wounds/abrasions

Biosimilar Name Reference Biologic (Brand)

Rank by ingredient cost in 2018 Manufacturer Route of

AdministrationApproved Indications/

Comments

Fulphila Neulasta 62 BGP Pharma ULC Subcutaneous

Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive antineoplastic drugs

First Time Generic Drugs (Notices of Compliance (NOCs) from November 28, 2018 to March 6, 2019)

New Biosimilars (Notices of Compliance (NOCs) from November 28, 2018 to March 6, 2019)

FIRST TIME GENERICS

NEW BIOSIMILARS

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Brand name Chemical name Manufacturer Dosage form Type of Line Extension Specifics /Comments

Adcetrisbrentuximab

vedotinSeattle Genetics Inc.

Intravenous injection

New indicationTreatment for patients with primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides.

Bosulif bosutinib Pfizer Canada Inc. TabletNew indication, new strength

For adult patients with newly diagnosed chronic phase Philadelphia chromosome positive chronic myelogenous leukemia.

Cystadrops cysteamineRecordati Rare Diseases

Canada Inc.Ophthalmic

solutionNew brand,

new dosage formTreatment of corneal cystine crystal deposits for patients with cystinosis.

Envarsus PA tacrolimus Endo Venturs Ltd.Extended release

tabletNew brand,

new dosage formProphylaxis of organ rejection in allogenic kidney or liver transplant.

Erelzi etanercept Sandoz Canada Inc.Subcutaneous

injectionNew indication

Reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in adult patients with psoriatic arthritis.

Foquestmethylphenidate

hydrochloridePurdue Pharma

Controlled release capsules

New indication

Treatment of Attention Deficit Hyperactivity Disorder in patients ≥6 years of age. Previously only indicated for use in adults (≥ 18 years of age).

Giotrif afatinib Boehringer Ingelheim Ltd. Tablet New indicationMonotherapy for patients with locally advanced or metastatic non-small cell lung cancer.

Humira adalimumab AbbVie Corp.Subcutaneous

injectionExpansion of

indication

Treatment of active moderate to severe hidradenitis suppurativa in adult and adolescent patients (12 to 17 years of age weighing ≥ 30 kg), who have not responded to conventional therapy (including systemic antibiotics). Previously only indicated for use in adults (≥ 18 years of age).

Treatment of chronic non-infectious anterior uveitis in pediatric patients from 2 years of age. Previously only indicated for use in adults (≥ 18 years of age).

Imbruvica ibrutinib Janssen Inc. Capsule New indicationIn combination with rituximab for the treatment of Waldenstrom macroglobulinemia.

Influvac Tetraquadrivalent

influenza vaccineBGP Pharma ULC

Intramuscular injection

New brand Prevention of influenza infection.

New Drugs and Product Line Extensions (Notices of Compliance (NOCs) from November 28, 2018 to March 6, 2019)

NEW DRUGS AND PRODUCT LINE EXTENSIONS

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Invokana canagliflozin Janssen Inc. Tablet New indication

Add-On Combination in patients with established cardiovascular disease to reduce the risk of adverse cardiovascular events in adults with Type 2 diabetes.

Jinarc tolvaptanOtsuka Canada

Pharmaceutical Inc.Tablet New indication

Slow the progression of kidney enlargement and kidney function decline in patients with autosomal dominant polycystic kidney disease.

Kalydeco ivacaftorVertex Pharmaceuticals

(Canada) Inc.Table, oral granules

New indication

Treatment of children with cystic fibrosis aged 12 months and older and weighing 7 kg to less than 25 kg who have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R. Previously limited to use in children 2 years of age and older. Removal of G970R CFTR mutation due to lack of efficacy.

KamRABhuman rabies

immunoglobulinKamada Ltd.

Intramuscular injection

New brandFor passive, transient post-exposure prophylaxis of rabies infection.

Lenvima lenvatinib Eisai Ltd. CapsuleNew indication, new strengths

First-line treatment for patients with unresectable hepatocellular carcinoma.

Orkambilumacaftor/ivacaftor

Vertex Pharmaceuticals (Canada) Inc.

Oral granulesNew indication, new dosage form

Expand indication to include individuals between 2 to 6 years of age. New dosage form of oral granules to support the expansion of the indication.

pdp-Amlodipineamlodipine besylate

Pendopharm (Division of Pharmascience Inc.)

Oral Solution New dosage formTreatment of mild to moderate hypertension and management of chronic stable angina.

Renvelasevelamer carbonate

sanofi-aventis Canada Inc.Powder for oral

suspensionNew indication, new dosage form

Control of hyperphosphatemia in adult and pediatric (≥6 years of age and a Body Surface Area (BSA) of ≥0.75 m2) patients with end-stage renal disease undergoing dialysis. Previously only indicated in adults. New dosage form of powder for oral suspension supports expanded indication.


(continued next page)

NEW DRUGS AND PRODUCT LINE EXTENSIONS (continued)

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Rexulti brexpiprazoleOtsuka Pharmaceutical

Co. Ltd.Tablet

New strength, new indication

Adjunct to antidepressants for treatment of major depressive disorder. Previously only indicated for schizophrenia. New strengths (combo packs) support titration phase of new indication.

Tolak fluorouracil Hill Dermaceuticals Inc. Topical CreamNew brand,

new strengthTreatment of actinic keratosis lesions of the face, ears, and/or scalp.

Verkazia cyclosporine Santen Inc.Ophthalmic emulsion

New brand, new strength

Treatment of severe vernal keratoconjunctivitis in children from 4 years of age through adolescence. Currently available as Restasis for dry eye disease at a lower strength.

Vonvendivonicog alfa /von Willebrand Factor

ComplexShire Pharma Canada

Intravenous injection

New brandTreatment and control of bleeding episodes in adults with von Willebrand Disease.

Xtandi enzalutamideAstellas Pharma Canada

Inc.Capsule New indication

Treatment for patients with non-metastatic castration-resistant prostate cancer.

Yervoy ipilimumabBristol-Myers Squibb

CanadaIntravenous

infusionNew indication

In combination with Opdivo for adult patients with intermediate/poor-risk advanced or metastatic renal cell carcinoma.

Zaxine rifaximin Salix Pharmaceuticals Inc. Tablet New indicationTreatment of irritable bowel syndrome with diarrhea.

NOC/c = marketing approval with conditions

Authors: Joen Reyes, Farah Belayadi, PharmD; Suzanne Easo, RPh, BScPhm; Mai Khalil, BSc (Pharm), Aaron Aoki, RPh, BScPhm, MBA, CDE, CRE


NEW DRUGS AND PRODUCT LINE EXTENSIONS (continued)

new drugs and pipeline news reviewed at the …...new drugs and pipeline news reviewed at the...

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