Washington Editor

Gilead Sciences Inc. on Tuesday released favorable clinical data on its newly acquired investigational HIV treatment, emtricitabine, and on long-term studies of its FDA-approved HIV drug, Viread.

Emtricitabine, also referred to as FTC or Coviracil, is a once-daily nucleoside reverse transcriptase inhibitor developed by Durham, N.C.-based Triangle Pharmaceuticals Inc. Gilead, of Foster City, Calif., acquired Triangle in a $464 million deal announced in December. (See BioWorld Today, Dec. 5, 2002.)

Viread, on the other hand, is a nucleotide analogue reverse transcriptase inhibitor approved for HIV in 18 countries including the U.S. Last year worldwide sales were $225.8 million.

On Tuesday at the 10th Conference on Retroviruses and Opportunistic Infections in Boston, French researchers presented 48-week data from a three-year, open-label, multicenter Phase III trial (ANRS 099 Alize) of FTC in 355 patients who at baseline had HIV RNA less than 400 copies/mL while receiving protease inhibitor (PI)-based antiretroviral therapy.

Erin Edgley, a spokeswoman for Gilead, told BioWorld Today the 48-week study shows that FTC suppresses HIV when taken as part of a once-daily, PI-sparing antiretroviral regimen.

In September, Triangle filed its new drug application for FTC under the name Coviracil (the name has yet to receive FDA approval). The application was based on positive data from a 48-week Phase III trial of 571 patients, plus supporting data from trials 302 and 303. (See BioWorld Today, Sept. 6, 2002.)

FTC's Prescription Drug User Fee Act action date is July 3.

According to a statement released by Gilead, at 48 weeks, 94 percent of patients receiving the once-daily regimen of FTC, didanosine and efavirenz had HIV RNA levels (viral load) less than 400 copies/mL, compared to 92 percent randomized to continue therapy in the PI-based arm (intent-to-treat population, assays performed at local laboratories at investigational centers).

The company reported that the proportion of patients with HIV RNA less than 50 copies/mL at week 48 was significantly higher in the once-daily treatment group. Ninety-five percent of patients in the once-daily group achieved this, compared to 87 percent in the PI arm (p=0.01). The median CD4 cell count increase was comparable in both arms, with an increase of 21 cells/mm3 for patients on the once-daily regimen and 13 cells/mm3 for those in the PI-based group.

Meanwhile, Gilead presented 96-week data from an ongoing, three-year, randomized, controlled trial (Study 903) of Viread in HIV patients.

Gilead said data demonstrates that that treatment-na ve patients who received Viread (tenofovir disoproxil fumarate) experienced substantially less lipodystrophy and lower elevations in fasting cholesterol and triglyceride levels, while achieving similar reductions in HIV viral load and increases in CD4 cell counts, compared to those who received stavudine (d4T). The study compares the efficacy and safety of a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a regimen of stavudine, lamivudine and efavirenz in 600 antiretroviral-na ve patients with HIV.

In the study, the Viread and stavudine arms reduced HIV RNA to less than 400 copies/mL in 82 and 78 percent of patients, respectively. Patients in both arms experienced substantial increases in mean CD4 cell counts, from the baseline mean of 276 to 537 cells/mm3 in the Viread arm and from the baseline mean of 283 to 549 cells/mm3 in the stavudine arm.

In other news from the conference:

• Mymetics Corp., of Annapolis, Md., presented data focused on the blocking ability of several of its peptides in vitro against a range of more than 10 strains of HIV. In certain cases, Mymetics said its peptides' in vitro activity matches or exceeds the entry inhibitor agents recently shown to reduce viral load in human clinical trials. For five of the HIV strains tested, peptides based on IL-2-homologous regions of HIV-gp41 were 28, 66, five, 13, and 37 times, respectively, more potent inhibitors of HIV replication than peptides derived from regions of HIV-gp41 that are not homologous to IL-2, it said.

• Panacos Pharmaceuticals Inc., of Gaithersburg, Md., reported data demonstrating the manner in which its drug candidate PA-457 attacks and disarms HIV. In a collaborative study with the National Institute of Allergy and Infectious Diseases, a unit of the National Institutes of Health in Bethesda, Md., Panacos demonstrated that PA-457 selectively blocks a key step in HIV maturation, a process that occurs as the virus buds from infected cells. Following PA-457 treatment, the released virus particles have a defective core structure and are non-infectious, pointing to a mechanism of action for PA-457 distinct from currently approved drugs.

• Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., reported data from a Phase II trial of its investigational HIV drug, PRO 542, corroborating the magnitude of viral load reductions observed in a previously completed clinical trial. The findings were correlated with viral susceptibility to the viral entry inhibitor prior to drug treatment, as measured by the PhenoSense HIV Entry assay from ViroLogic Inc., of South San Francisco. Also, patient virus collected six weeks after treatment initiation showed no evidence of having developed resistance to PRO 542, an antibody-like molecule designed to target and neutralize the virus in the bloodstream.

• Tanox Inc., of Houston, said results of its Phase Ia safety trial showed that TNX-355 was well tolerated and showed a significant decrease in viral load in patients with treatment-refractory HIV infection. TNX-355, a humanized, non-immunosuppressive anti-CD4 monoclonal antibody, is designed to directly block cellular infection by HIV by binding to the CD4 receptor on host cell surfaces. HIV binding to the CD4 receptor is an initial step in virus progression.

• Vertex Pharmaceuticals Inc., of Cambridge, Mass., and GlaxoSmithKline plc, of London, reported 48-week data from two Phase III trials, named NEAT and SOLO. The studies of treatment-na ve patients with HIV infection evaluated the resistance profile of the investigational protease inhibitor (PI) GW433908 (908) dosed twice a day or 908 boosted with the PI ritonavir (908/r) dosed once a day compared to the PI nelfinavir (NFV) BID. In the SOLO study, no patients in the 908/r arm, out of 32 subjects experiencing virologic failure or with ongoing viral replication, had detectable primary or secondary PI mutations. But 27 of 54 patients (50 percent) in the NFV arm developed primary or secondary PI mutations. In the NEAT study, five of 29 patients (17 percent) who experienced treatment failure in the unboosted 908 arm had mutations characteristic of APV resistance. NFV-selected mutations were observed in seven of 26 patients (27 percent) who experienced virologic failure in the nelfinavir arm.