Washington Editor

The FDA cleared the accelerated approval application for Fuzeon, a first-in-class fusion inhibitor for HIV-1 developed by Trimeris Inc., and partner F. Hoffmann-La Roche Ltd.

Approved under fast-track priority review guidelines, Fuzeon (enfuvirtide), in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

Unlike traditional HIV products that are designed to work inside the cell, Fuzeon is designed to work outside the cell and block the virus from entering. "But the most important feature is that Fuzeon is active against viruses that have developed resistance to the existing drugs," Dani Bolognesi, CEO of Durham, N.C.-based Trimeris, told BioWorld Today.

"We are living in the shadow of an epidemic of resistant viruses in HIV, and the best way to attack a virus that has developed resistance to existing drugs is to develop new drugs with different mechanisms of action that effectively combat multidrug resistant viruses," Bolognesi said. "I believe that Fuzeon is able to achieve that and I think it provides a large number of patients, who at the moment are in desperate need of new treatment options, some hope."

Trimeris' stock (NASDAQ:TRMS) fell $2.90 Friday to close at $41.05.

The companies hope to launch Fuzeon (formerly T-20) by the end of March, Bolognesi said. As for the price, several weeks ago Roche, of Basel, Switzerland, said it would charge European patients participating in certain early access programs about $20,000 a year for Fuzeon. When asked about it Friday, Bolognesi said patients should expect the price to be in that range. "Roche said it would like to have a global price instead of wide fluctuations in different markets," he said.

Indeed, Wall Street expects Fuzeon to be a big earner. The first year out, Dennis Harp, biotechnology analyst with Deutsche Bank-North America in New York, told BioWorld Today global sales should reach $59 million, compared to $342 million in 2004 and up to $900 million at peak. While Trimeris is developing a second-generation fusion inhibitor (T-1249), Harp said Fuzeon is expected to be the only product in its class for the next few years.

First-year sales are a little low, he said, because the companies likely will find it difficult to keep up with demand.

"This is an important new breakthrough therapy," Harp said. "Yes, it will be a more expensive product, but it is injectable and complicated to manufacture. Initially, it will be directed at patients whose virus has developed resistance to many, if not all, of the currently available drugs, so for many patients Fuzeon is a rescue. It will delay and perhaps prevent the onset of AIDS."

In a previous conversation with BioWorld Today, Robin Fastenau, Trimeris' manager of corporate communications, explained that Fuzeon is "one of the most complex and challenging molecules ever chemically manufactured by the pharmaceutical industry on such a large scale. There are more than 100 production steps, which is 10 times more than any other antiretroviral drug. It also requires 45 kg of raw materials to manufacture 1 kg of Fuzeon." (See BioWorld Today, Feb. 25, 2003.)

Harp said most HIV/AIDS drugs cost from $3,000 to $13,000 per year.

The FDA is the first regulatory authority to clear Fuzeon, a twice-daily subcutaneous injection. However, European approval is expected in the first half of this year.

Meanwhile, Bolognesi said FDA approval triggers a milestone payment for Trimeris, but would not disclose the exact amount. The overall deal with Roche dates back to 1999 when Bolognesi and Tom Matthews, Trimeris' senior vice president of research, sought a partnership to help develop T-20, which they had discovered while working as researchers at Duke University in Durham.

Trimeris and Roche share development expenses 50-50 in the U.S. and Canada. Outside those areas, Roche will fund all development costs and will pay Trimeris royalties on net sales of Fuzeon and T-1249, which is slated to enter Phase II trials this year.

Regulatory submission for Fuzeon was based on data from two 24-week Phase III pivotal studies of about 1,000 patients. The trials were TORO 1 (T-20/Fuzeon vs. Optimized Regimen Only), conducted in North America and Brazil, and TORO 2, conducted in Europe and Australia.

According to statements released by the companies, the studies showed that treatment-experienced patients receiving Fuzeon as part of an optimized background regimen (individualized combination of anti-HIV drugs) experienced greater immunologic improvements and were twice as likely to achieve undetectable plasma levels of HIV (HIV-1 RNA of <400 copies/mL, compared to patients receiving an individualized regimen alone). Also, those patients with two or more active drugs in their background regimen were more likely to achieve undetectable levels of HIV.

Bolognesi said the TORO 1 and TORO2 trials would continue to 48 weeks, a time period necessary to gain full FDA approval.