Post-BIO News Roundup

Been focusing on Chicago and this year’s BIO extravaganza all week? Here’s a sampling of news you might have missed.

Pirfenidone rejected

In a surprisingly twist, FDA refused to approve InterMune’s lung treatment pirfenidone, despite a positive recommendation from its advisory committee. The agency wants another lengthy trial to better demonstrate pirfenidone is effective at treating idiopathic pulmonary fibrosis, a debilitating and ultimately fatal lung disease for which there are no approved treatments in the U.S. or Europe. InterMune’s stock fell over 75% on the news. Check out this piece in Forbes’ health care blog on whether FDA is these days less likely to listen to its advisory panels.

Birth Control Pill Exalted

The mainstream media celebrated as “The Pill” turned 50. Technically, they’re celebrating the 50th anniversary of its approval by FDA. C&EN covered the chemistry story of the pill in “The Top Pharmaceuticals That Changed The World” special issue, back in 2005. Don’t miss the classy 1950s era photo of Carl Djerassi.

Resveratrol Trial Halted

A GlaxoSmithKline clinical trial studying a reformulated version of resveratrol was suspended on April 22 due to safety concerns, but company officials say the complications may or may not be related to the drug. The big question remains-what does this all mean for the effort to make drugs out of resveratrol, the trace component of red wine that’s been touted as a cancer fighter and a fountain of youth in a bottle?

Resveratrol research has been in the spotlight a lot lately, not just for good reasons. GSK got the reformulated resveratrol (also called SRT-501) when it acquired biotech company Sirtris in 2008, to the tune of $720 million. Sirtris based its business around evidence that resveratrol turned on enzymes called sirtuins. The belief was that this activity could underlie some of resveratrol’s beneficial effects. Sirtris developed other drug candidates based on this idea that the company says look nothing like resveratrol, and some of those entitites are in clinical trials as well.

But the sirtuin connection has been called into question on multiple occasions.

And now, with news that some patients in the resveratrol clinical trial developed cast nephropathy, a condition that can lead to kidney failure, the Wall Street Journal Health Blog is wondering aloud whether resveratrol’s 15 minutes of pharmaceutical fame are coming to an end.

GlaxoSmithKline officials say they are studying the data further, and that they stopped the trial “out of an abundance of caution”, according to the Wall Street Journal. The trial was conducted in patients with multiple myeloma, and apparently, cast nephropathy is common in myeloma patients. Commenters at “In the Pipeline” (which, by the way, got a shout-out from WSJ for breaking the story) have discussed this at length.

So how do you untangle whether the condition was caused by resveratrol, by bortezomib, or by something else? This study assessed the reformulated resveratrol either alone or in combination with the already-approved multiple myeloma drug bortezomib. It would be easier to untangle the data if there were a bortezomib-only group, but there isn’t. It isn’t even random who got what course of therapy. Here’s the relevant part of the trial description:

After the first two cycles of SRT501 treatment and review of the efficacy and response analysis, any subject who exhibits stable disease or better with SRT501 monotherapy may continue on SRT501 monotherapy (5.0 g/day) for an additional two cycles. If, after the first two cycles of SRT501 monotherapy, a subject exhibits PD, then that subject will receive bortezomib (1.3 mg/ m2 on Day 1, Day 4, Day 8, and Day 11 in a 21 day cycle) in conjunction with SRT501 (5.0 g/day).

This is a really tiny study, and other trials of the reformulated resveratrol have been completed. Still, given the trial’s design, I don’t see how it’s possible to figure out what really happened here- though feel free to correct me in the comments if you think I’m wrong.

Telaprevir Resistance

A Bloomberg story highlighted a recent study by researchers at Los Alamos Laboratory that highlighted the risk of the Hepatitis C virus developing resistance to Vertex Pharmaceutical’s telaprevir. The study showed that up to 20% of viral particles in most common strain of Hepatitis C developed resistance to telaprevir in just two days. The resistance story isn’t new to anyone following drug development in HCV, and the tone of the article–that somehow telaprevir was expected to one day be used on its own–felt misleading. There was a time when scientists thought it might be possible for telaprevir alone to quell HCV—that time has long since passed.

In fact, the emergence of resistance in Vertex’s own two-week studies of the use of telaprevir as a monotherapy led FDA to put strict guidelines on trials for all direct-acting antivirals. Today, companies can only study an HCV antiviral as a monotherapy in humans for three days.

Vertex will soon unveil Phase III studies of telaprevir in combination with the current standard of care, pegylated interferon and ribavirin, and will first seek FDA approval as an add-on to that regimen. As C&EN’s cover story this week outlines, everyone in the HCV world acknowledges that if the only hope of getting rid of the current standard of care is to develop a cocktail of several antivirals with different targets, and therefore different resistance profiles.

Indeed, Vertex is about to start a trial testing telaprevir, a protease inhibitor, in combination with VX-222, a polymerase inhibitor. Likewise, Bristol-Myers Squibb, Roche, and Gilead Sciences are all exploring combinations of small molecules to shut down the infection. Whether two drugs will be enough to overcome resistance remains to be seen.

Author: Lisa Jarvis

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