With new positive data coming out of a Phase II trial of its lead HIV drug, Incyte Corp. is embarking on a second larger study to determine the long-term effects of Reverset.

The Wilmington, Del.-based company previously reported data showing 30 treatment-na ve patients demonstrated a marked reduction in viral load after 10 days of monotherapy treatment. At the 15th International AIDS Conference in Bangkok, Thailand, a Northwestern University researcher on Monday presented more promising data, this time in 10 treatment-experienced patients who received the therapy for 10 days.

"The most important thing that we showed here is that we saw very good responses also in people who have been heavily treated with antiretrovirals and were failing their previous regimens," said Rich Levy, Incyte's senior vice president of drug development.

The patients previously had failed a mean of 5.5 regimens and half of them had four or more thymidine analogue mutations at the start of Reverset treatment. Reverset demonstrated equal effectiveness in patients failing regimens of Epivir (Biochem Pharma Inc.) and Viread (Gilead Sciences Inc.). The most common adverse events were cold symptoms, headache and tiredness.

Reverset, a nucleoside analogue reverse transcriptase inhibitor, is being developed as a once-a-day oral therapy for use in combination with other antiretroviral drugs. In the Phase II trial, called Study 202, it was well tolerated at all doses studied and demonstrated a clinically significant reduction in viral load for all treatment-na ve patients and seven of eight patients who failed previous therapies.

Data showed that the mean reduction in viral load among the eight treatment-experienced patients receiving the highest dose was 0.8 log¹⁰ copies/mL. In the treatment-na ve patients who received either the 50-mg, 100-mg or 200-mg once-daily dose, the reduction ranged from 1.67 to 1.77 log¹⁰ copies/mL. Among patients receiving the highest dose, 87.5 percent of treatment-na ve patients and 50 percent of treatment-experienced patients achieved viral loads less than 400 copies/mL. The therapy was well tolerated and displayed no significant adverse events.

From his hotel in Bangkok, Levy told BioWorld Today that the company is enrolling about 180 patients in the second six-month Phase II trial called Study 203.

"We expect to be enrolled sometime by the end of the year," he said. "Hopefully we'll be able to report results sometime around a year from now."

After that, the company would move Reverset into a Phase III trial. If all goes well, it would file a new drug application in late 2006 and seek priority review.

Levy said the drug might offer an advantage over existing therapies.

"Based on looking at viruses in vitro, we expect to have a different resistance profile than other nucleosides on the market," he said.

In vitro studies have shown that Reverset inhibits replication of drug-resistant HIV strains commonly seen after treatment with zidovudine and lamivudine.

Pam Murphy, Incyte's vice president of corporate communications, said the company is considering development of Reverset as a first-line or second-line therapy. The potential market in the U.S. and Europe would be between $250 million and $500 million annually, she said.

Behind Reverset, Incyte is working on a CCR2 antagonist small molecule for inflammation that entered the clinic in May, and a small-molecule cancer compound that should enter the clinic early next year, Murphy said.

Incyte licensed Reverset in September 2003 from Atlanta-based Pharmasset Ltd., which was spun out of Emory University. Incyte gained exclusive development, manufacturing and marketing rights in the U.S., Europe and other unnamed markets. (See BioWorld Today, Sept. 9, 2003.)

Incyte's stock (NASDAQ:INCY) dropped 34 cents on Monday to close at $6.46.

In other news from the conference:

• Gilead Sciences Inc., of Foster City, Calif., said a special issue of the Journal of the American Medical Association published for the conference included data from two separate studies evaluating the efficacy and safety of Viread and Emtriva, compared with stavudine, in combination with other antiretroviral agents. Study 903, a three-year, international, randomized, double-blind clinical trial that evaluated 600 patients, showed that Viread and stavudine had comparable success in suppressing HIV, while certain adverse events attributed to mitochondrial toxicity were observed more frequently among patients receiving stavudine. Study 301a, a randomized study in which patients received once-daily Emtriva or twice-daily stavudine, in combination with once-daily efavirenz and didanosine, showed that the Emtriva regimen was superior in primary and secondary efficacy and safety endpoints. Viread is a nucleoside reverse transcriptase inhibitor, while Emtriva, stavudine and didanosine are nucleoside reverse transcriptase inhibitors to treat HIV. Gilead expects an FDA decision in September on its new drug application for a fixed-dose combination of Viread and Emtriva.

• GlaxoSmithKline plc, of London, and Boehringer Ingelheim GmbH, of Ingelheim, Germany, signed a letter of intent for an accelerated development program for a co-package of Combivir and Viramune for chronic treatment of HIV infection in the developing world. The companies are seeking regulatory approval for development of the co-package to increase treatment options for HIV. Combivir is a combination tablet containing Epivir (lamivudine, 3TC) and Retrovir (zidovudine, AZT). Viramune (nevirapine) is a non-nucleoside reverse transcriptase inhibitor. Both are indicated in combination with other antiretroviral agents to treat HIV.

• Guava Technologies Inc., of Hayward, Calif., said data from three study sites showed that results obtained using its EasyCD4 and EasyCD8 Assays for the enumeration of human CD4+ T cells and CD8+ T cells showed excellent correlation with the standard, clinically approved BD MultiTEST (flow cytometry) assay from Becton, Dickinson & Co., of Franklin Lakes, N.J. A plot of percent difference between EasyCD4 and EasyCD8 methods and the MultiTEST method showed no trends in bias across the observed range. The median percent differences for the three sites ranged from -1.8 percent to 8.3 percent for CD4, and from -13.1 percent to -8.6 percent for CD8. Similarly, the median between-site variability of the EasyCD4 and EasyCD8 was calculated to be 10.6 percent and 10.8 percent, respectively.

• Trimeris Inc., of Durham, N.C., presented data showing Fuzeon (enfuvirtide) suppresses HIV and provides continuous increases in immune cells over a period of 96 weeks. Fifty-six percent of treatment-experienced patients who began using Fuzeon at the outset of the study were successful in completing 96 weeks of treatment. The data presented were from an analysis of two randomized, open-label trials that enrolled about 1,000 HIV patients previously treated with an average of 12 antiretrovirals. Patients who were randomized to receive a Fuzeon-based regimen had significantly lower levels of the virus and higher CD4 counts, compared to those randomized to a regimen without Fuzeon. No new safety issues were identified, and patients in the Fuzeon arm experienced less diarrhea, nausea and fatigue associated with antiretroviral therapy. The most common adverse event was injection-site reactions. Fuzeon received accelerated approval from the FDA in March 2003. It also is approved in the European Union, Switzerland and Canada.

• Vertex Pharmaceuticals Inc., of Cambridge, Mass., and GlaxoSmithKline plc, of London, presented data showing that HIV treatment regimens containing the protease inhibitor Lexiva (fosamprenavir calcium) dosed with ritonavir or lopinavir and ritonavir were effective in suppressing HIV in patients who had failed prior PI-containing regimens. Data are based on 48-week results of a Phase III randomized trial that enrolled patients who had experienced virologic failure while receiving one to two prior PI regimens. There was little difference between the Lexiva/r and lopinavir/r study arms in the proportion of patients with virologic failure. Vertex and GSK co-discovered Lexiva, which is indicated for the treatment of HIV in adults in combination with other antiretroviral medications.