Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations

Sherman, Kenneth E.; Fleischer, Russell; Laessig, Katherine; Murray, Jeffrey; Tauber, William; Birnkrant, Debra

doi:10.1002/hep.21985

Cited by 22 publications

(13 citation statements)

References 29 publications

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“…Among adverse events possibly or probably related to thymalfasin, most were mild and resolved without sequelae, and only one (nipple pain) occurred in 10% or more of thymalfasin-treated patients. These results are consistent with those of previous clinical studies, in which thymalfasin has been shown to have an excellent safety profile [32,[45][46][47][48]. When evaluating new agents for HCC, it is crucial to determine that they do not worsen outcomes and survival due to associated toxicity, compared with placebo or existing treatments [49,50].…”

Section: Discussionsupporting

confidence: 88%

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

et al. 2009

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Purpose Patients with advanced hepatocellular carcinoma (HCC) have few treatment options. Thymalfasin (thymosin a-1) is an immunomodulator that may increase response to ablative therapy through direct anti-tumor action or enhanced protection against infections. We compared transarterial chemoembolization (TACE) plus thymalfasin with TACE alone for unresectable HCC. Methods In this phase II, randomized trial, 25 patients received either TACE plus thymalfasin (1.6 mg SC, 5 times weekly; n = 14) or TACE alone (n = 11) for 24 weeks. Response was defined as transition to transplant eligibility or lack of disease progression through week 72. Survival was assessed through 24 months post-treatment. Results Eight of fourteen (57.1%) patients in the TACE ? thymalfasin group versus 5 of 11 (45.5%) patients in the TACE-only group became responders (P = 1.0). Four of fourteen TACE ? thymalfasin patients versus none of 11 TACE-only patients became eligible for transplant. Median overall survival time was 110.3 weeks for the TACE ? thymalfasin group versus 57.0 weeks for the TACE-only group (P = 0.45). Seven patients in each group experienced serious adverse events; there were no bacterial infections in the TACE ? thymalfasin group versus 4 in the TACE-only group. There were 3 deaths in the TACE ? thymalfasin group and 5 in the TACE-only group. Conclusions In patients with unresectable HCC, TACE ? thymalfasin resulted in numerically higher rates of survival and tumor response, including transplant candidacy, with fewer bacterial infections, than TACE alone. Treatment regimens for HCC including thymalfasin as an immunomodulator should be evaluated in larger trials.

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Section: Discussionsupporting

confidence: 88%

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

et al. 2009

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“…The regulatory decision-making process is based on the strength of data rather than theoretical considerations of benefi t. Important lessons from the HIV drug development arena will infl uence regulatory decisions with regard to HCV and include 1) the co-development of drugs in rational combinations (different mechanism of action and resistance profi les) makes sense and should be encouraged; 2) durability of response and tolerability of regimens are important; 3) concepts of resistance and cross-resistance for a class must be evaluated; and 4) the need for development and validation of biomarkers that are predictive of clinical benefi t. Unfortunately, no written guidelines from the US Food and Drug Administration (FDA) currently exist to guide HCV drug development, although there was one communication from an FDA advisory committee meeting in 2006 [30]. The result is a chaotic and unpredictable development paradigm for the many agents under clinical development.…”

Section: Regulatory Considerationsmentioning

confidence: 98%

STAT-C: New therapies cannot get here fast enough

Morelli

Nelson

2009

Curr hepatitis rep

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“…The FDA considers HIV/HCV co-infected patients as a special population for HCV drug development and mandates studies addressing drug–drug interactions and safety [24]. At this time, clinicians must make treatment intervention decisions without availability of complete data regarding background ART interactions with the approved DAAs.…”

Section: First-generation Direct-acting Antivirals (Daas)mentioning

confidence: 99%

Hepatitis C and HIV Co-Infection: New Drugs in Practice and in the Pipeline

Jennings

Sherman

2012

Curr HIV/AIDS Rep

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HCV/HIV coinfection continues to represent a serious health issue with risk of liver disease progression and development of hepatocellular carcinoma. Pegylated interferon with ribavirin is approved for treatment but results are suboptimal and tolerability poor. First-generation HCV protease inhibitors appear to significantly improve HCV treatment response in the setting of HIV infection. Interactions with HIV protease inhibitors have been documented, but the significance of this in terms of adverse reactions and HCV or HIV viral breakthrough remains uncertain. Next generation agents hold the promise of even better efficacy, with improved dosing schedules and perhaps decreased risk of drug:drug interactions.

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Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations

Cited by 22 publications

References 29 publications

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

STAT-C: New therapies cannot get here fast enough

Hepatitis C and HIV Co-Infection: New Drugs in Practice and in the Pipeline

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