Belgium’s Solvay and partner Wyeth’s hopes of launching bifeprunox, their investigational compound for schizophrenia, next year in the USA have been scuppered by US regulators.

The companies have received an action letter from the US Food and Drug Administration which rejects their New Drug Application for bifeprunox, an atypical antipsychotic reviewed for the acute treatment of schizophrenia, as well as the maintenance of stable adult patients. The agency stated that bifeprunox demonstrated effectiveness in the long-term maintenance study, and indicated that a second study could be sufficient to support a maintenance claim for the compound, but has concluded that “efficacy data, when compared to reference drugs, were not sufficient for approval”.

The FDA also requested further information regarding the human metabolism of bifeprunox, and information “regarding a complex case of a patient who died while participating in one of the trials”.

Laurence Downey, chief executive of Solvay’s US operations, said the firms will work with the FDA to address its comments and pursue the approval of bifeprunox as soon as possible, while Wyeth’s chief medical officer Gary Stiles claimed that the drug “offers the possibility of a new treatment approach for patients where maintaining stability is challenged by the metabolic consequences frequently encountered with long-term therapy”. He added that “we continue to support the development of the compound and the approach," and the firms are looking to speak to the agency shortly to discuss the design of this additional study.

Analysts not overly surprised at rejection

The FDA’s rejection is a major blow to both firms but did not come as a great surprise. Ahead of the FDA’s decision, analysts were stating that Wyeth’s forecasts that bifeprunox would be a $1 billion drug were a little premature and Barbara Ryan at Deutsche Bank predicted that the compound is "likely to face some challenges at the FDA due to onerous side effects and no real demonstrated efficacy advantages”. After the negative response from the agency, she said that bifeprunox would have “a very limited role in a crowded category that will include several widely used generic products”. Other analysts agreed that even if the drug wins approval for the maintenance of schizophrenia, as opposed to acute treatment, that market seems limited.

Solvay shares closed down 5% to 100.60 euros on the announcement while another bifeprunox partner, Danish drugmaker Lundbeck, saw its stock slip 3.2%. The latter firm announced in November 2005 that it was delaying filing for approval of the treatment in Europe until 2008 as it carries out additional Phase III testing.

However Wyeth was the worst hit, and its shares fell slightly over 6% to $46.59. The bad news about bifeprunox comes less than a month after the FDA requested additional clinical trial data for Pristiq (desvenlafaxine), the follow-up to its blockbuster depression drug Effexor (venlafaxine), that could push back the launch of that drug by a year or more. The delays to Pristiq and now bifeprunox spell serious problems for Wyeth as they were expected to buffer declining sales of the $3.5 billion-a-year Effexor when it comes off patent in 2010.

Wyeth, ViroPharma hepatitis trial flounders

There was some more bad news for Wyeth after the firm and partner ViroPharma announced that they will discontinue dosing patients in Phase II trial of its hepatitis C treatment candidate HCV-796, citing safety concerns. The decision follows a review by a joint safety review board which found that around 8% of patients receiving HCV-796 in combination with pegylated interferon and ribavirin had elevated liver enzymes.

"While substantial efforts are ongoing to continue analysis of these data, we consider it to be in the best interests of patients to discontinue dosing with HCV-796 at this time," said Colin Broom, ViroPharma's chief scientific officer. The firm’s chief executive, Michel de Rosen, noted that "this is a clear disappointment in light of the exciting antiviral activity observed to date in this study” and “although this represents a potential setback for hepatitis C patients…this decision was absolutely the right thing to do". ViroPharma shares sank almost 15% on the news to $8.70.