Though mostly off the front pages these days, the war against HIV goes on - and last week a new therapeutic recruit showed some of its colors, as Incyte Corp. unveiled data from a Phase IIb trial with the once-daily pill Reverset, yet another nucleoside analogue reverse transcriptase inhibitor (NRTI).
Incyte called the news positive, but Wall Street balked, shearing away more than 15 percent of the company's stock value by day's end.
Study 203 tested Reverset in 199 patients at 25 sites in three doses, 50 mg, 100 mg, and 200 mg, with the largest dose gaining a 54 percent response rate compared to 40 percent in placebo patients.
One of the goals was to find the right dose for the Phase III trial, noted Pam Murphy, vice president of corporate communications and investor relations for Incyte, and the company has done that.
"We only had experience with 10 days," she told BioWorld Financial Watch, referring to an earlier Phase II study with Reverset in 30 patients, and the company wanted to prove a lasting, safe effect. That happened, too.
A third met goal was to uncover subsets of patients who might benefit especially from Reverset, which is designed to be used in combination with other drugs in treatment-experienced patients.
At two weeks, when Reverset was added to therapy, patients gained a 0.7 log drop in viral load overall as compared to placebo patients (who showed no change), and a 1.1 log drop in the subset of patients not using in their background treatment regimen GlaxoSmithKline plc's 3TC or Emtriva, the HIV drug also known as FTC, from Gilead Sciences Inc. Both are deployed as first-line treatments.
At 16 weeks in the overall group, when the 200-mg dose of Reverset was used as add-on therapy in either an optimized or non-optimized regimen, patients given the Incyte drug came up with a 1.2 log drop in viral load vs. a 0.8 log drop for placebo patients and a 1.4 log drop in viral load in the subset of patients not also getting 3TC or FTC, vs. a 0.5 log drop for placebo patients.
The trial was not geared to produce the kind of "p" value data that might be expected from a Phase III study, Murphy said - and that might be what disappointed some investors - but it yielded plenty of important data for the design of that study, expected to begin by year's end.
The overall group in Study 203 gained a 54 percent response rate vs. a 40 percent response rate as compared to placebo, with response defined as more than a 1.0 log drop in viral load. In patients not getting 3TC or FTC as background, the difference was 80 percent vs. 25 percent on placebo.
At 16 weeks in the non-optimized group, patients given the 200-mg dose got a 0.6 log drop in viral load as compared to non-optimized placebo patients, who achieved a 0.1 log reduction, and a 1.5 log drop in the subset of patients not getting 3TC or FTC, as compared to a 0.3 log increase in the non-optimized placebo patients.
"Robust" results in non-3TC/FTC patients proved surprising, Murphy said, adding that Reverset "could be" used as a monotherapy, though it's not being developed as a stand-alone drug.
The latest data were disclosed at the International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro, Brazil. Earlier results with Reverset came during the XV International AIDS Conference in Bangkok, Thailand, and more came last fall at the Interscience Conference on Antimicrobial Agents and Chemotherapy. The drug even worked against the notoriously difficult-to-treat resistant and mutated HIV strains - specifically, in those patients whose NRTI therapy (3TC and Viread [tenofovir disoproxil fumarate], also from Gilead) was failing.
Sadly, the market for HIV drugs is solid. A report this summer from the Centers for Disease Control and Prevention said the number of Americans living with the infection has, for the first time, exceeded 1 million, though about one-fourth don't know it.
Incyte has a collaborative licensing agreement for Reverset with Pharmasset Inc., signed in the fall of 2003, that gives Incyte exclusive rights in the U.S., Europe and certain other markets to develop, manufacture and market the drug.
There's more in the pipeline, such as INCB3284, an oral CCR2 antagonist at the Phase II stage for inflammatory disease such as rheumatoid arthritis and for diabetes. In Phase I, Incyte has an oral sheddase inhibitor for cancer, INCB7839, to be used first in combination with Genentech Inc.'s Rituxan (rituximab) for non-Hodgkin's lymphoma, and then tested against other tumor types.
Formerly known as Incyte Genomics, the firm has steadily retooled itself as a drug development concern. At the start of this year, Incyte sold its proteomics information business based in Massachusetts to the German firm Biobase GmbH.
For the moment, investor eyes are on Reverset.
Jason Napodano, senior biotechnology analyst with Zack's Independent Research, wrote in a June report that Reverset "may be relegated to second-line HIV patients," with physicians preferring to prescribe other, leading NRTI drugs first.
"In this scenario, we believe Reverset will compete with other add-on NRTI's, such as Emtriva and Epivir. The problem in this case is that Reverset will not be able to replace Emtriva and Epivir because of the existence of new combination pills."
GSK has a combo pill containing Retrovir (zidovudine) and Epivir called Combivir, and Gilead has developed a combination Viread/Emtriva pill called Truvada.
"Our belief is that physicians will prescribe Truvada and Combivir first, and then try Reverset if the patient is resistant or failing to show adequate response," Napodano wrote. "This would place the peak sales estimate closer to $200 million."
Napodano and others are likely to have more to say about Reverset - and Incyte in general - after a conference call Tuesday, during which company officials will discuss second-quarter earnings.