Expectations for HCV Therapy with Small Molecules: An Activist Perspective

Transcription

1 Expectations for HCV Therapy with Small Molecules: An Activist Perspective Tracy Swan, Treatment Action Group Second International Symposium on Hepatitis Care in Substance Users September 15-16, 2011 Brussels, Belgium

2 Disclosure This talk was intended to be from a patient perspective I don t have hepatitis My current substance use can only be described as unimpressive I am employed by a non-profit AIDS research and policy think tank in other words, I m a professional activist Therefore, this talk is from an activist perspective

3 From Representation to Participation What is needed to facilitate participation of HCV patients who use drugs?

4 About HCV Activism TAG s Hepatitis/HIV Project draws from the core values and history of AIDS activism. Social justice issues are inherent in drug development; hence oversight of HCV clinical trials is a major focus of my work. I work domestically and internationally, in collaboration with other activists from the viral hepatitis, HIV, harm reduction and human rights communities, people living with hepatitis C, clinicians, researchers, policy makers, regulatory agencies, pharmaceutical companies and other service providers.

5 Drug Development Approval Pyramid Cirrhosis, HIV+, HCV TX experienced DDIs, and studies in hepatic/renal impairment Mild-to-moderate liver scarringpopulations with limited DDI potential (HIVnegative, no OST) Population least risky to study: people with HCV, in otherwise flawless physical & mental health

6 < Risky populations Approval Drug Development Pyramid high-risk trials for people traditionally ineligible for clinical trials Asses safety in renal/hepatic impairment Characterize DDIs (if necessary), to facilitate and commence, if indicated, inclusion of people on ART, OST, psychotropic medications, etc, and people with cirrhosis

7 Activism & HCV Drug Development for People Using OST Assess risks/benefits of HCV treatment in the context of OST/ongoing drug use Failure to enroll current and former drug users/people on OST supports justification for withholding treatment In the context of collapsing public health systems, or urgent and unmet medical need, clinical trials may be the best or only option for access to HCV treatment

8 The Implied Population Special populations listed in regulatory guidance documents on HCV drug development: Decompensated liver disease and/or pre-transplant Post-transplant Hepatic impairment HIV/HCV coinfected patients PEG IFN and RBV intolerant patients, Patients with prior DAA experience Pediatric Sources: EMA: Guideline on Clinical Evaluation of Medicinal Products for Treatment of Hepatitis C. Draft for Consultation. January FDA: Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment. Draft Guidance. September 2010.

9 Gaps in HCV Drug Development: special populations in phase 3 trials Population Boceprevir Telaprevir Decompensated cirrhosis Compensated Cirrhosis 0% 0% ~9% naive 12% experienced Null responders 0% 27% ~ 8% naïve 25% experienced OST 0% 0.5% or 11/2,290 HIV/HCV coinfected 99; ongoing 60; ongoing

10 Drug-Drug Interactions: High Stakes Methadone Buprenorphine HIV antiretrovirals Antidepressants Hormonal contraception Anti-diabetics Lipid lowering drugs etc..

11 OST: Drug-Drug Interactions with DAAs EMA..priority should be given to studies of coadministration with other drugs used in the management of HCV, HIV, liver transplantation, depression and substance abuse, as well as oral contraceptives. Within these areas, essential drugs that have a foreseen potential for interaction, should be prioritized for study. Such data is expected to be available at the time of the marketing authorisation. FDA No mention of methadone or buprenorphine DDI studies

12 HCV Protease Inhibitors & OST Boceprevir: methadone and buprenorphine DDI study is not recruiting yet (as of 9/14/11) Telaprevir: methadone use w/monitoring; buprenorphine study completed--results not available (as of 9/14/11)

13 OST & The Next Wave of DAAs DDI studies: 1/13 protease inhibitors (methadone) 0/6 NS5a inhibitors 1/9 Non-nucleoside polymerase inhibitors (methadone) Drug-drug interactions may limit the use of certain DAAs in people on OST (especially methadone)

14 At These Prices Regimen Low End High End Boceprevirbased Reference: $ 45,227 to $ 80,675 32,954 28, 591 AUD 44,001 CAD 44,705 58,787 38, 197 AUD 78,493 CAD 79,746 Telaprevirbased Reference: $65,322 to $81,445 47,597 41, 299 AUD 63, 574 CAD 64, ,350 51, 510 AUD 79, 293 CAD 80,544

15 A Clinical Wish List Tolerability (IFN-free) Regimens that are safe to use with prescribed and illicit drugs Convenience Lack of food restrictions Coformulations/ lowest possible pill burden Once daily dosing ( HEP-TRIPLA ) Forgiving drugs to forestall resistance Shortest possible regimen Earliest possible stopping rule Innovative delivery systems (nanotechnology)

16 Infrastructure/Delivery Strategize/share information on delivering treatment in innovative ways to anticipate diminishing funding for social services Expand use of non-medical personnel (treatment educators, peers) Work closely with patient advocacy groups

17 Research Issues Registration trials usually exclude or grudgingly include people who use drugs (although rarely) Lack of clarity around concerns: safety, adherence? Lack of effort to address these, i.e. DDIs, training/ selecting experienced investigators Use of drug testing, which screens out the wrong people Under-utilization of multidisciplinary care No peer involvement Criteria are vague, and subjective (up to the investigator, but no guidance/information provided)

18 Next Steps Design trials to identify cost-effective strategies for HCV treatment and its delivery Develop research guidelines Create training for investigators Work with peers to help enroll and retain study participants Protest against drug testing during HCV clinical trials (unless there is reasonable basis for it) Advocate for: inclusion of people on OST in clinical trials development of compounds unlikely to interact with OST (esp methadone) access to buprenorphine