Hepatitis C Drug Pipeline

It seems like every week, companies are issuing press releases about their new hepatitis C drug candidates—protease inhibitors, polymerase inhibitors, immunomodulators, you name it and it seems like everyone and their cousin is cooking something up in their labs. And every few months you’ll see a batch of reports from scientific conferences touting new data—this week it’s Digestive Disease Week (DDW) in New Orleans, last month it was the 39th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin. How do you keep up, and how do you make sense of it all?

If you want to hear about all the latest drug development news and data, here are three websites (in alphabetical order) that do a good job of covering the waterfront:

HCV Advocate/Hepatitis C Support Project

HIVandHepatitis.com

National AIDS Treatment Advocacy Project (NATAP)

All three sites compile news stories and conference reports, and all three let you sign up for email updates. Each is well worth checking out.

HCV Advocate also maintains a chart [PDF version] of hepatitis C treatments in clinical development (clinical = human studies; preclinical = in vitro/test tube and animal studies), last updated in February. Another chart that includes compounds in preclinical development is available here, last updated in November.

Now, as for making sense of it all….

First, some perspective: It typically takes several years of preclinical research before a company brings a compound into human studies. And then, it takes several years of human studies (say, 5-8 years) before there’s enough data for the Food and Drug Administration (FDA) can determine that the drug is safe and effective enough to be licensed for marketing and wide-scale use. Human studies are divided into phase I, phase II, and phase III trials – studies start off small to test safety and dosing, then get larger to look at whether the drug actually works, and collect safety data in more people using the drug for longer periods of time.

I’ll write about what happens in each phase in a future post (for now, see ‘From Test Tube to Patient: New Drug Development in the United States’ [PDF file] from the FDA, and ‘Clinical Trials’ and ‘FDA Overview’ [PDF versions] for an HIV activist perspective on the drug development and approval process from the Summer 2002 issue of Research Initiative/Treatment Action! [RITA!], published by Houston’s Center for AIDS: Hope & Remembrance Project). But for now, keep in mind that very few compounds make it through to FDA approval – most fail in the preclinical stage, and a high proportion fail in early clinical trials.

That being said, HCV Advocate just published a good review [PDF version] of the HCV drug development pipeline by Dr. Paul Pockros of the Scripps Clinic. The article covers new interferons and interferon delivery systems, immunomodulators and anti-fibrotics (treatments to prevent or reverse fibrosis), ribavirin-like molecules, and molecular therapies (e.g., protease and polymerase inhibitors). I’d quibble with some of his conclusions, and note that a couple of investigational drugs he discusses, levovirin and Heptazyme, are no longer being pursued. But it’s a solid, concise overview of the field.

I've also written (or co-written) a couple of recent overviews of the hepatitis C pipeline:

Looking forward to 2004: treatment for hepatitis C: A brief review of new hepatitis C drugs in development from aidsmap

Proliferation of Polymerase Inhibitors and Other Tales from the HCV Crypt: A longer review, with some general considerations for drug development, from TAGline (co-written with Tracy Swan)

(I've contributed a few chapters on hepatitis C drug development and basic science for Tracy's upcoming Hepatitis C and HIV/HCV Coinfection Report, to be released by the Treatment Action Group [TAG] this summer. The report will summarize available research on hepatitis C and offer policy recommendations and highlight key areas for research and advocacy.)

Coming soon: My short and selective list of some new hepatitis C drugs to keep an eye on -- focusing on drugs further along in clinical trials, that show signs of offering advantages to current treatment. I’ll cover the following drugs (company names in parentheses): viramidine (Valeant), merimepodib (Vertex), NM-283 (Idenix), R803 (Rigel), isatoribine (Anadys), and Actilon (Coley). And I’ll give an update on HCV protease inhibitor research in a separate post.

Comments

[Raquel Garijo]

Could I have the patent of R803 inhibitor of HCV?