West Coast Editor
Idenix Pharmaceuticals Inc.'s FDA-ordered clinical hold on the nucleoside inhibitor valopicitabine for hepatitis C virus comes just a month after encouraging Phase II data, and probably means death for the drug also known as NM283, thanks to gastrointestinal side effects that the agency found serious enough to stop development.
"I have to tell you that we were very surprised - Idenix and Novartis - by their perspective," Jean-Pierre Sommadossi, chairman and chief executive officer of Cambridge, Mass.-based Idenix, told investors during a conference call.
Wall Street didn't like it, either. Shares of Idenix (NASDAQ:IDIX) closed Friday at $3.57, down $2.22, or 38.3 percent.
"We're evaluating our options for the program, but I want to tell you up front that I am not optimistic" about valopicitabine's viability, Sommadossi said.
Douglas Mayers, chief scientific officer for Idenix, noted that the company recognized the GI problems.
"I think we reached the same quantitative conclusions," he said, but Idenix believed valopicitabine was worth another test to find the right dose. The FDA disagreed.
In spring 2006, Idenix reduced dosing in a Phase IIb trial in a bid to dodge the GI side effects, and the firm's stock fell 28 percent on the news. Basel, Switzerland-based Novartis exercised its option to license the product anyway, in a deal valued as high as $525 million. Under a collaboration begun in 2003, Novartis holds the right of first refusal on Idenix's entire pipeline. (See BioWorld Today, March 30, 2006.)
An increasingly crowded HCV space has led the FDA to consider tweaking its clinical requirements for compounds designed to treat the disease, and the Antiviral Drugs Advisory Committee convened late last year specifically to discuss the issue. (See BioWorld Today, Nov. 1, 2006.)
The FDA cleared Idenix/Novartis' nucleoside analogue for hepatitis B virus, Tyzeka (telbivudine), in October, and the drug is called Sebivo outside the U.S.
Last month, Foster City, Calif.-based Gilead Sciences said Study 103, its second Phase III trial of the anti-HIV drug Viread (tenofovir disoproxil fumarate) in treating HBV, met its primary efficacy endpoint. The data showed that Viread is non-inferior to the company's once-daily antiviral drug Hepsera (adefovir dipivoxil) among patients with "e" antigen (HBeAg)-positive chronic disease.
"We will have to wait and see" what Viread's progress means for Tyzeka, Sommadossi said, adding that not all the data have been presented in a scientific forum. "Let's not forget in our Phase IIIb/Phase IV program [with Tyzeka] we initiate combination therapy actually with tenofovir. We believe that the future of treatment for hepatitis B is going to be a combination of a nucleoside and a nucleotide," so a combination of Tyzeka and Viread could be "ideal," he said.
Mayers said HBV therapy will become a "many-year proposition" in which blocking resistance and getting response that lasts will be critical, and a combo therapy could provide "durable responses for a decade or more."
In the works by Idenix are a non-nucleoside reverse transcriptase inhibitor being evaluated in Phase I for HIV. The HCV discovery push goes on, and includes a preclinical, second-generation nucleoside polymerase inhibitor, and programs with an HCV non-nucleoside polymerase inhibitor and an HCV protease inhibitor.
As of June 30, 2007, Idenix had approximately $160 million of cash, cash equivalents and marketable securities. Ronald Renaud, Idenix's recently appointed chief financial officer, said guidance remains unchanged, and the firm expects to end 2007 with $100 million to $110 million.
Asked about in-licensing possibilities, Renaud said the firm is "very comfortable with what we have here and what we're investing in, in terms of our internal pipeline, and I think that's going to be our primary focus on a going-forward basis. In terms of the guidance for Tyzeka, we still stand behind [an estimate of] total worldwide sales of $20 million" for the year, he said.