West Coast Editor

Positive Phase II data with Gilead Sciences Inc.'s HIV drug GS 9137 (elvitegravir) came as no surprise - the company already had disclosed plans for Phase III trials - and results suggested the integrase inhibitor could have an edge in dosing convenience over its would-be competitor from Merck & Co. Inc., already in Phase III trials.

James Loduca, manager of public affairs for Foster City, Calif.-based Gilead, said the company is reviewing the Phase II data with the FDA, and has not decided when the Phase III study will begin.

Presented at the Conference on Retroviruses and Opportunistic Infections in Los Angeles, the Phase II data showed statistically superior reductions in viral load among HIV-positive, treatment-experienced patients given 125 mg of GS 9137 once daily, boosted with 100 mg of ritonavir, compared to those receiving a boosted protease inhibitor (usually darunavir or tipranavir), both in combination with an optimized background regimen.

The trial started out dosing at 20 mg, 50 mg, and 125 mg, but the 20-mg patient group was switched at the eighth week to 125 mg due to high rates of virologic failure. A monitoring panel also advised Gilead to change the protocol slightly, letting patients in the GS 9137 arm add darunavir or tipranavir to their background regimens. But only 15 percent did so before 24 weeks passed, thus mostly preserving the head-to-head match of GS 9137 versus protease inhibitors - "particularly before week 16," Loduca said. "Prior to that, only four patients had added a protease inhibitor, so it's the most pure comparison."

At 16 weeks and 24 weeks, patients in the GS 9137 arm showed statistically significant reductions in viral load versus control patients, and the mean time-weighted average drop from baseline viral load was 1.7 log in the GS 9137 125-mg arm versus 1.2 log in the control arm. Ninety-two percent of patients on high-dose GS 9137 had a greater than 1 log viral load reduction at 24 weeks compared to 61 percent of patients in the control arm, which also was statistically significant.

At 24 weeks, 36 percent of GS 9137 patients had a viral load of fewer than 50 copies/mL, compared to 27 percent of patients in the control arm. GS-9137 increased CD4 count, too, by 57 cells/mL compared to 53 cells/mL for the control group.

GS 9137, also known as JTK-303, was licensed by Gilead from Japan Tobacco Inc. in March 2005. Gilead has exclusive rights to develop and commercialize the compound in all countries of the world, excluding Japan where JT retains rights.

The once-daily dosing might give Gilead a leg up on Trenton, N.J.-based Merck's twice-daily Isentress (raltegravir), also known as MK-0518, though Isentress (also an integrase inhibitor) is about a year ahead of GS 9137 and is not boosted. Merck offered Isentress data at the CROI meeting, too, with 16-week results from a Phase III study proving the compound effective and well tolerated.

Although the single daily dose might be more important in treatment-na ve patients, Gilead needs to do more clinical work to better understand how GS 9137 would work in that population compared to treatment-experienced patients. But integrase inhibitors, making up a novel class of drugs, are particularly important for patients who have run out of options, Loduca noted.

Gilead has enjoyed a strong year so far. IMS Health reported that Truvada, the combination HIV drug made of the company's Viread (tenofovir disoproxil fumarate) and Emtriva (emtricitabine), sold $64.6 million in January, beating estimates Lazard Capital Markets' estimate and implying $216.5 million in sales for the first quarter, compared to Lazard's guess of $192.2 million.

Atripla, which combines Truvada with New York-based Bristol-Myers Squibb Co.'s HIV compound Sustiva (efavirenz), sold $52.7 million in January, according to IMS, implying $187.5 million for the first quarter. Lazard had estimated $171.5 million. Viread sold $24.1 million in January, and Hepsera (adefovir dipivoxil) for hepatitis B sold $9.2 million, both in line with Lazard's estimates.

Last month, the FDA granted priority review for the Gilead's new drug application related to the pulmonary arterial hypertension therapy, ambrisentan, with a target review date of June 18. Gilead filed a new drug application in December for the endothelin receptor antagonist, which previously won orphan designation for PAH.

In other news from CROI:

• Idenix Pharmaceuticals Inc., of Cambridge, Mass., said preclinical data from two novel non-nucleoside reverse transcriptase inhibitors for the treatment of HIV-1, IDX899 and IDX989, demonstrated potent and selective activity in vitro against a broad panel of wild-type isolates, and the drugs retained potency against panels with various single and double NNRTI mutations. Both compounds exhibited good oral bioavailability with a favorable pharmacokinetic profile, Idenix said. Separately, the firm said Sebivo (telbivudine) won approval in China as a once-a-day treatment, taken orally with or without food, for the treatment of chronic hepatitis B virus. Telbivudine is approved in the U.S. and certain other countries under the name Tyzeka. The drug is partnered in co-promotion arrangements in the U.S. and Europe with Novartis Pharma AG, of Basel, Switzerland. (See BioWorld Today, Oct. 27, 2006.)

• Trimeris Inc., of Morrisville, N.C., said 98 percent who received the Merck's Isentress along with Fuzeon (enfuvirtide) and a darunavir boost achieved undetectable levels of HIV (less than 400 copies/mL of blood). Such a high response rate has never been seen in patients who have developed resistance to at least one agent in each of the first three classes of antiretrovirals. Fuzeon was co-developed by Trimeris and Basel, Switzerland-based F. Hoffmann-La Roche Ltd.