Nov. 2 2010 - 2:02 pm
By ROBERT LANGRETH
In the heated race to develop new hepatitis C drugs that boost the cure rate, Wall Street thinks Vertex Pharmaceuticals has a slightly better drug than a rival entry from Merck, and thus will garner the large majority of sales.
Both companies were talking a good game as they presented new data at a conference of liver specialists wrapping up today(11/2). “The case for boceprevir is compelling,” Merck research head Peter Kim said in an brief phone interview with Forbes. “I am really excited about the profile we have. It is going to have a significant impact.” He touted his drug as “the only drug” whose trials have shown that shorter regimens are possible in patients who failed previous therapy. (Both drugs have been able to shorten the treatment regimen in some patients receiving initial treatment.)
“We think our data is the leading data,” counters Vertex chief medical officer Robert Kauffman. The Vertex drug’s cure rate of up to 75% “sets quite a high bar for the competition.” While Merck and Vertex are touting the ability of their drugs to cure difficult-to-treat “null responders” whose viral levels barely budged on existing therapy, Kauffman argued that Merck’s trial used potentially looser criteria that included patients who “would not fit the standard definition of null responder”.
But even with shorter regimens, both drugs will still have to be given with interferon alpha, the two-decade old antiviral drug made by Merck and Roche that causes nasty flu like side-effects, including fever and fatigue. It is a general antiviral agent that does not specifically target the hepatitis C virus at all.
This stands in contrast to AIDS where patients get cocktails of targeted pills that keep the HIV virus at bay for years. Company’s like Bristol-Myers and Gilead Sciences are trying hard, but no one has yet come up with a cocktail of antiviral pills that can kill off the hepatitis C virus without the need for interferon.
One reason is that the flat geometry of the hepatitis C protease protein made it is difficult target to hit with small-chemical drugs. Direct antiviral drugs for hep C are only now coming out after over a decade of work.
A bigger reason, says Vertex’s Kauffman, is that hepatitis c is a hugely efficient reproducer. It produces 1 trillion new viral particles a day–a far greater replication rate than HIV. Hepatitis C also makes many mistakes when it copies itself.
All this means that patients already have mutant viral particles inside their bodies that are likely to be resistant to direct antiviral drugs. Giving a cocktail of one or two antiviral drugs will smash down the viral levels in the short term, but ultimately will select for the resistant viruses in the long term. Interferon helps, despite the nasty side effects, because it works by a general antiviral mechanism that avoids these problems.
It is a numbers game. Until researchers can come out with a potent enough antiviral combo to account for the massive numbers of mutations that hepatitis c virus can produce, interferon will remain part of hepatitis C treatments.
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