new hcv treatments any access to resource limited...

New HCV treatmentsAny access to resource‐limited countries ?

Maud LemoineMRC, The Gambia Unit, West Africa

10 REASONS TO OPEN ACCESS TO NEW HEP‐C TREATMENT IN RLC

A SPECIAL LOOK AT AFRICA

1‐ HCV infection is a public health issue in RLC

Jules L, NEJM 2008, Lavanchy, Clin MicrobiolInfect, 2011, Madhava, V Lancet 2002

SSA has the highest WHO estimated regional HCV prevalence : 5.3% = 32 million individualsHIV: 23.5 million (UNAIDS 2012)

P: 3% Median prevalence: 2.2 to 13.8%With large difference between three regions:Central Africa : 6% (Cameroun +++13.8%)East Africa and South Africa: 1.6%West Africa: 2.4%

170 million people infected with HCV‐ 3% of the world pop.3‐4 million new infections each year

HCV is a leading cause of deaths worldwide

• 350,000 annual deaths • 30% of cirrhosis• 20% of Hepatocellular carcinoma 5th cancer worldwide

Lavanchy, Liver Int, 2009Globocan, 2008Salmon‐Ceron D, 2009Gellad, ZF AVT 2012

1) 80% of deaths related to liver cancer occur in resource‐poor regions2) HCC: the third malignancy in poor countries

Liver‐related deaths occur in resource‐limited countries

GLOBOCAN, 2008, Lemoine M. Future Virol 2013

In Africa, HCC is a major killer

Jemal A, WHO/IARC, Cancer 2012

HCV: 20-50% of the cases according to the HCV local endemicityKirk GD, Hepatology 2004, Perz JF, J Hepatol 2006

Data on HIV‐HCV co‐infection are lacking and conflicting

• Cameroun: HCV‐HIV prevalence: 12.4% (n=169 HIV Pos)

Laurent C, HIV Med, 2010

• Nigeria, Jos University Teaching Hospital:n=19 408 HIV Pos (2014‐2010) HCV‐HIV prevalence: 11.3%

Ladep N, W J Gastro 2013

• Ghana: 3.6% (n=138 HIV subjects)Sagoe, KW J Med Virol 2012

• Senegal: 1.6% (95%[0.6‐3.5])Diop‐Ndiaye H, J Med Virol 2008

Liver disease has become a major cause of death in HIV patients

The D.A.D study group, AIDS. 2010 Jun 19;24(10):1537‐48.

11.5% hepatitis related

Resource‐limited countries will facethe same burden of liver‐related morbi‐mortality !

UNDETECTABLE FOR HCV

AS WELL ???

Only 5% of the 170 million HCV-infected people are aware of their infection

Thomas DL, Lancet 2010;376:1441‐1442Thomas DL, AVT 2012

Risk factors of HCV infection in Africa

Kandeel AM, BMC Infect Dis, 2012

Is injecting drug abuse an issue in SSA ?

Estimation of IDU number per countries‐UNODC 2008, RaguinG, Girard PM Trop Med Int Health 2009

0.5 to 3 million IDU

Dakar and urban areasn=1324 IDUSHIV: 5.2%HCV : 23.3% Ba I et al. 2011Tine J et al. Poster 20,interest 2013

NairobiHCV:22.2% in IDU(n=314)

Muasya,T . East Afr Med J 2008



2‐ New innovative diagnostic tools adapted to the resource‐poor settings

Innovative diagnostic tools

Rapid Testing‐ Point‐of‐care tests‐ Salivary rapid testing

Yaari,A J Viral Methods 2006

Easier assessment of the infection and the liver disease‐ Dry‐blood spots (HCV viral load quantification/genotyping)

Tuaillon E Hepatology 2010

‐ Portative Fibroscan (Echosens)‐ Portative sonography



3‐ HCV infection is a CURABLE disease

Treatment has been significantly improved% of p

atients w

ith su

staine

d virological respo

nse (SVR

)

IFN

24 W

70

50

30

20

10

60

40

IFN

48 W

IFN+RBV

24 W

IFN+RBV

48 W

PEG‐IFN+RBV

48 W

0

80

90

IFN = Interferon‐αPEG‐INF = Peg‐Interferon‐αRBV = RibavirinW = weeksPEG = PEG‐IFN‐α

PEG‐IFN+RBV+new IP

TelaprevirOr Boceprevir

INF‐free regimens12 weeks

? 95‐100% SVR

2002

2011

1999

2014

0

10

20

30

40

50

60

70

80

90

Naive Prior relapsers Prior partialresponders

Prior nullresponders

Peg‐RibaPeg‐Riba + TelaprevirPeg‐Riba + Boceprev

SVR has been significanly improved with the first generation of Direct Antiviral Agents (DAA)

SVR(%)

+30%

But....Add-on drugs adds on costs, complexity

and side effects Boceprevir:

• Anemia• Nausea• Dysgeusia• Neutropenia• Headache

Telaprevir:• Anemia• Nausea• Rash, pruritus• Anorectal

signs/symptoms• Diarrhea

30 000 €25 000 €

Drug‐to Drug interactions is an issue=> interaction with ARV

Second generation of Direct Antiviral Agents (DAA)ongoing INF‐free therapy trials

INF‐free regimens Naive Genotype 1 patients

1. Sulkowski M, et al. AASLD 2012. Abstract LB‐2. 2. Gane E, et al. AASLD 2012. Abstract 229.3. Kowdley KV, et al. AASLD 2012. Abstract LB‐1. 4. Everson G, et al. AASLD 2012. Abstract LB‐3.

Sofosbuvir (Nuc) + daclatasvir(NS5A) + RBV x 24 wks

100

80

60

40

20

0

SVR4

, 12, or 2

4 (%

)

n/N =

100[1]

15/15

2‐3 DAAs + RBV

Sofosbuvir (Nuc) + daclatasvir (NS5A) x 24 wks

Daclatasvir (NS5A) + asunaprevir (PI) +BMS 791325 (NNI) x 12 wks

2‐3 DAAs, No RBV28/29

97[1] 94[4]

15/16

98[3]

77/79

ABT‐450/r (PI) + ABT‐333 (NNI)+ ABT‐267 (NS5A) + RBV x 12 wks

25/25

100[2]

Sofosbuvir (Nuc) + GS‐5885 (NS5A) + RBV x 12 wks

Treatment TreatmentDuration Population Results

Sofosbuvir + ledipasvir 8 weeks

GT 1 treatment‐naïve

95% (19/20) SVR 8

Sofosbuvir + ledipasvir + RBV

8 weeks GT 1 treatment‐naïve

100% (21/21) SVR 8


GT 1 treatment‐naïve

100% (19/19) SVR 4


GT 1 treatment‐experienced

95% (18/19) SVR 4

Sofosbuvir + ledipasvir + RBV

12 weeks GT 1 treatment‐experienced

95% (20/21) SVR 4

Gilead Press release-Phase 2 study

May 2, 2013

Sofosbuvir (Nuc) + RBV x 12 wks

Sofosbuvir (Nuc) + Daclatasvir (NS5A) ± RBV x 24 wks

Danoprevir (PI)/ritonavir + pegIFN + RBV x 12‐24 wks

100

80

60

40

20

0

SVR1

2 or 24 (%

)

n/N = 25/26

GT2 GT3Experienced

92[1]

85/92

GT2 Naive

96[2]

27/28

88[3]

14/16

GT4/6Naive

GT4Naive

97[4]

29/30

1. Jacobson Ira M, EASL, 2013 Positron study 2. Sulkowski M, et al. AASLD 2012. Abstract LB‐2. 3. Hassanein T, et al. AASLD 2012. Abstract 230. 4. Hezode C, et al. AASLD 2012. Abstract 760.5. Nelson D, EASL 2013 , fusion study Fusion study SVR12

Sofosbuvir (Nuc) + RBV + pegIFN x 24 wks

Genotypes 2‐6

96[5]

37[5]

14/38

68[1]

57/84

GT3 Naive GT2/3 Naive

Interferon therapy is not adapted to the African setting

1) INJECTABLE

2) REQUIRING COLD STORAGE (2° to 8°C)

3) SIDE‐EFFECTS FatigueFlu‐like syndromepsychiatric effects NeutropeniathrombopeniaAnemia

4) AFRICAN HCV‐infected SUBJECTS:Genotype 1 and 4,non‐C/C IL28B

=> LOWER RESPONSE to Peg‐INF‐ RBV therapy

Interferon‐free regimensalso affordable to resource‐limited countries



4‐ Hep.C treatment is feasible in RLC

Ford N et al , Bull WHO 2012

n=12, 213 patients93 studies from 17 RLC

SVR

The adherence and the rate of side‐effectswere similar to those reported in

the western studies



5‐ In the absence of vaccine, treatmentis preventive

Durier N et al Plos One 2012

Treatment is cost‐effectiveGelad, Antiviral Therapy 2012



6‐ A recent political will


7‐ A duty to treat

1‐ Access to Health is a Fundamental Human RightUniversal Human Right Declaration and WHO constitution, 1948

2‐ States and Supranational institutions Moral Obligation to ensure access to health for all

3‐Medical and scientific knowledge= common good accessible for all

4‐ United Nations Millenium Development Goals (2000)« ….to provide access to affordable medicines in developing countries in cooperation with pharmaceutical companies”

• Since 1995, the Trade‐Related Aspects of Intellectual Property Rights

(TRIPS) agreements (World Trade Organisation)

20‐years patent protection to pharmaceutical products

Incentives needed for Research and Development ?

90% of investments for R&D concern 10% of the richest world’s

population

Hoen et JAIDS 2011, Lemoine M, Future Virol 2013

Yet…..

“There is no evidence that the implementation

of the TRIPS agreements in developing countries

will boost research on diseases affecting these

countries”

Commission on Intellectual Property Rights, WHO, 2006


8‐We must and we can challenge the drug market

The Doha Declaration (2001)the TRIPS Agreements “can and should beimplemented in a manner (...) to protect public healthand to promote access to medicines for all”.

Each country has the right to declare any disease asa urgent public health issue

=> And to generate „compulsory licences“ to makepatented drugs available at affordable prices in the"public health interest."

The example of India

From 4,000 euros to 150 euros/month

The Egyptian experience

• Reiferon Retard®(MINAPHARM company)Biosimilar of PegINF

• Price has been negociated and divided by 15 over the last years

0

10000

20000

30000

40000

50000

60000

70000

2008 2009 2010 2011

1500

3000

Cost of treatment (€)N of patients treated/y

http://www.medicinespatentpool.org

India and China80 % of the worldwide medicine production

Lula da Silva set up the first ARVfactory in AfricaMaputo, Nov. 2010

Factory launched in July 2012


9‐ Lessons from HIV/AIDS experience

1) COST:• In 2000: ART: $10,000‐15,000/patient/year• Today < $100/year

In 2000, only 0.1% received ARV in Africa Today, almost 50%

2) COMPLEX and POLITICALLY DISREGARDED

• “Many people in Africa have never seen a clock or a watch their entire lives. If you say one pm in the afternoon, they do not know what you are talking about“.

Andrew Natsios, former USAID director, 2000

• Until 2002, WHO did not to consider ARV as essential medicines

L‘ histoire se répète ....


10‐ Respond to the civil society

4‐5 million HIV‐HCV infected peopleMostly living in RLC

International conference on HIV/AIDS, Washington 2012

CONCLUSION

• Hepatitis C in RLC is a neglected public health issue• Screening and access to treatment are critical• High time to implement programs and guidelines on Hep.C adapted to the local poor settings

• The new era of new DAA is a PERFECT opportunity to improve the burden of Hep.C and HCC in RLC

Time for action We should not let DAA being

Discriminating Access to Antivirals

AckowledgmentsFrance Isabelle CheminPierre‐Marie GirardKarine LacombeMaimuna MendyGilles RaguinChristopher WildFabien Zoulim

UK (Imperial College London) Mark ThurszSimon Taylor‐RobinsonHelen HolmesDebbie GarsideGraham CookMary CrosseyShevanthi NayagamTorben Kimhofer

The GambiaRamou NjieHarr NjaiGibril NdowYusuke ShimakawaSaydiba TambaMavis Foster‐NyakoAbdullah JattaUmberto D‘allessandroTumani CorrahMakie TaalMustapha KhalilOusman Nyan

SenegalMourtalla KaSouleyman MboupCoumba Toure‐KaneAmina Sow

NigeriaNimzing LadepMarie DuguruYakubu FiyaktuVirginia SaleSolomon BanwatEdwin Adoga

Ivory CoastSerge Eholie

new hcv treatments any access to resource limited...

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