Trimeris Inc. and Hoffmann-La Roche Inc. on Tuesday filed a new drug application for Fuzeon, a fusion inhibitor designed to treat HIV patients.
Fuzeon (enfuvirtide) is a twice-daily subcutaneous injection formerly known as T-20.
Trimeris, of Durham, N.C., and Roche, of Nutley, N.J., referred to the drug as "the front-runner in a new class of anti-HIV drugs."
Indeed, Dennis Harp, a biotechnology analyst with Deutsche Bank-North America in New York, told BioWorld Today that Fuzeon is the only such drug that prevents HIV from entering the T cells. "All the other drugs work after viral entry has occurred and they work by preventing the virus from replicating. This actually prevents viral entry."
As a result, Harp expects Fuzeon is bound for FDA approval early next year. He anticipates peak annual sales to reach $600 million worldwide.
The companies have sought six-month priority review status and should be notified within two months as to whether they receive it.
Officials at Trimeris remain in a quiet period following a proposed public offering in late August. Trimeris registered to sell 2.3 million shares at $48.29 per share for up to $111 million in proceeds. (See BioWorld Today, Aug. 26, 2002.)
On Tuesday, Trimeris' stock (NASDAQ:TRMS) closed at $46.18, up 35 cents.
Dani Bolognesi, Trimeris' CEO, released a prepared statement saying, "Fuzeon was designed from the outset to block HIV replication in a completely different manner than current antiretroviral drugs, while not substantially adding to the toxicity of other agents. Fuzeon's unique mode of action is designed to block HIV before entering the human cell and if approved, it will represent the first of a new class of anti-HIV drugs in seven years."
Bolognesi and his colleague, Tom Matthews, discovered T-20 as researchers at Duke University. Later, the two founded Trimeris, and in 1999, signed a deal with Roche to develop the drug.
Georges Gemayel, vice president at Roche, released a prepared statement saying filing the NDA is an important step, and Heather Van Ness, a spokeswoman for the company, discussed the clinical trials with BioWorld Today.
"These studies have been conducted in patients who are treatment-experienced who have taken multiple drugs and developed resistance to several different combinations," she said. "We conducted the trials in this way because the greatest need for new treatments at this time in the developed world is in the area where patients have developed resistance and are running out of options."
According to a Trimeris-Roche press release, 78 percent of patients receiving treatment in North America and Europe are infected with a strain of HIV that has developed resistance to one or more anti-HIV drugs.
The NDA is based on two 24-week international Phase III trials referred to as TORO 1 and TORO 2 (T-20 vs. Optimized Regimen Only). Trimeris said data indicated that combination therapy with Fuzeon reduced HIV to undetectable levels in the blood in at least twice the percentage of patients as those who did not take the drug. (See BioWorld Today, July 9, 2002.)
TORO 1 included 491 patients who had been treated with 12 antiretroviral agents. Fifty-two percent of patients receiving Fuzeon experienced a 1.0 log10 or greater reduction in HIV levels. TORO 2 enrolled 504 patients who had previously been treated with 11 antiretroviral drugs. Twenty-eight percent of patients who received Fuzeon in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 14 percent receiving an optimized background regimen alone (p<0.0001).
Harp said it's not likely that Fuzeon will be used only in patients who have developed resistance. "Because the drug is administered as an injection twice a day, it is less convenient than the other medications that are available. While it is not a requirement that it is given to patients who have developed resistance, in practice, most patients will be put on the oral agent first and once resistance develops, they would move on to Fuzeon. I would say it can be administered at home; it's the type of injection that would be similar to what an insulin-dependent diabetic might self-administer."
Also on Tuesday, the companies said they validated the first of three commercial batches of active ingredient for Fuzeon at the Roche Colorado manufacturing facility.
The companies initially entered a partnership to develop Fuzeon and T-1249 in 1999. (T-1249, also a fusion inhibitor, is in Phase I/II studies.) But in June 2001, the two extended the partnership to equally fund research for additional candidates.
As part of the deal, the companies 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 the net sales of these products.
Roche would not discuss the amount it has paid Trimeris, but in April, Bolognesi told BioWorld Today the figure was about $12 million. (See BioWorld Today, April 19, 2002.)
The companies plan to file for approval in Europe before the end of September.