Looking for a more traditional Fuzeon approval, Trimeris Inc. and F. Hoffmann-La Roche Ltd. submitted longer-term data to the FDA for review.

The partners filed 48-week safety and efficacy data from two pivotal studies of the HIV drug, a fusion inhibitor, to support full approval. The application comes nine months after the agency approved Fuzeon (enfuvirtide) in an accelerated process following submission of 24-week data. The drug is indicated for combination treatment with other antiretroviral agents for HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. It also is approved in the European Union, Switzerland and Canada and generated about $18.3 million in sales through Sept. 30. (See BioWorld Today, March 17, 2003.)

The latest findings point to its use as part of combination regimens to improve virologic and immune responses for a period twice as long as originally shown. And the partners said there is no waiting list for the drug, which costs about $20,000 per year, as they have sufficiently scaled-up manufacturing operations to meet demand.

"If granted, a full approval for Fuzeon would be significant because it would recognize the durability of efficacy and safety results seen through 48 weeks in the pivotal trials," Robin Fastenau, manager of corporate communications at Durham, N.C.-based Trimeris, told BioWorld Today. "Achieving a long-term, durable response has been one of the most significant challenges in managing treatment-experienced patients."

She added that researchers and clinicians see the long-term data as indicative of establishing Fuzeon-based combination regimens as a new standard of care for such a patient population. An endorsement would lend itself toward potentially boosting drug-related revenue, though Trimeris and Basel, Switzerland-based Roche have not publicly forecasted potential peak sales guidance.

Among the findings submitted to the FDA are data showing that at 48 weeks, 30 percent of patients on a Fuzeon regimen had undetectable levels of HIV (less than 400 copies/mL of blood) compared to 12 percent on a regimen without Fuzeon. Also, 80 percent of patients who achieved undetectable levels of the virus at 24 weeks maintained the response at 48 weeks.

On average, patients receiving a Fuzeon-based regimen experienced an increase of twice as many CD4 immune cells from baseline as those achieved by patients on a regimen absent Fuzeon (increase of 91 cells/mm3 in the Fuzeon arm vs. 45 cells/mm3 in the control arm) at 48 weeks. In addition, patients on a Fuzeon-containing regimen had 32 weeks of virological benefit, compared to 11 weeks for patients on regimens without Fuzeon.

All the results, reported at various scientific meetings this year, were statistically significant (p<0.0001). (See BioWorld Today, July 16, 2003.)

Among patients with less advanced disease (less than 100,000 copies of HIV per mL of blood and immune cell count greater than 100 cells/mm3), 47 percent of those on Fuzeon-based regimens achieved undetectable levels of HIV, compared to 18 percent for those not receiving Fuzeon (p<0.05). In that group, patients receiving a Fuzeon-based regimen had a mean CD4 immune cell increase of 103 cells/mm3 from baseline compared to 51 cells/mm3 for patients receiving a regimen without Fuzeon.

Patients with the most advanced disease (baseline viral load greater than 100,000 copies of HIV per mL of blood and immune cell count less than 100 cells/mm3) were more than three times as likely to achieve undetectable levels of HIV with a Fuzeon-based anti-HIV drug regimen vs. patients receiving a regimen without Fuzeon (15 percent vs. 4 percent, p<0.05). Among the same patients, those taking a Fuzeon-based regimen experienced twice the CD4 immune cell increase from baseline as patients receiving a regimen without Fuzeon (mean CD4 immune cell increase of 84 cells/mm3 vs. 40 cells/mm3, respectively).

Still in the pipeline, Trimeris and Roche are developing T-1249, a second-generation fusion inhibitor designed to be more potent than Fuzeon. The product is scheduled to enter Phase II testing in the coming year.

Trimeris' stock (NASDAQ:TRMS) fell 32 cents Tuesday to close at $20.28.

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