Editor

When spoken, "ICAAC" might sound like a cat coughing up a hairball, but the well-known acronym for the Interscience Conference on Antimicrobial Agents and Chemotherapy held yearly by the American Society for Microbiology often means plenty of news, as biotechnology firms offer data from pet research projects.

This year, another, even more familiar acronym took center stage: HIV. Still a deadly scourge, HIV is targeted by many laboratories. Gilead Sciences Inc. has front-line therapy in the bag, thanks to Truvada, the combination of Viread (tenofovir disoproxil fumarate) and Emtriva (emtricitabine), but there's a scramble in the area of second-line treatments.

ICAAC provided a glimpse at many of those, and Gilead, of course, was on hand with results. The firm bolstered top-line results disclosed earlier from studies known as COMET, which stands for "Combination of Efavirinz and Truvada," and RAVE, which means "Randomized Abacavir Viread Evaluation."

Efavirenz, brand-named Sustiva, is the non-nucleoside reverse transcriptase inhibitor from Bristol-Myers Squibb Co., with which Gilead is collaborating to create a once-daily, triple-drug regimen that pairs the drug with Truvada. Abacavir is branded Ziagen by GlaxoSmithKline plc.

Gilead in February presented preliminary 48-week data from RAVE in Boston at the 12th Conference on Retroviruses and Opportunistic Infections. The study compares abacavir and Viread as replacement for a thymidine analogue as part of highly active antiretroviral therapy in 105 HIV-infected patients with lipoatrophy and controlled HIV RNA.

In November, the firm offered 24-week results from COMET at the 10th European AIDS Conference in Dublin, Ireland, showing that Truvada yielded a decrease in viral load in treatment-experienced patients who switched from twice-daily Combivir (made up of lamivudine 150 mg/zidovudine 300 mg), also from GSK.

Posters on both studies at this year's ICAAC, held in Washington, bolstered first reports and validated investor faith in Gilead, which in October reported third-quarter earnings that beat consensus estimates, thanks to the growth of the firm's HIV franchise. The company tallied net income of $179.2 million, or 38 cents per share, for the three months ending Sept. 30, compared to net income of $113.2 million, or 25 cents per share for the third quarter of 2004. Total revenues hit $493.5 million, with much of that coming from sales of Truvada and Viread.

Consensus estimates had projected total revenues of $487.6 million and earnings per share of 37 cents.

What's hottest in HIV? Integrase inhibitors, if you ask Andrew McDonald, analyst with ThinkEquity Partners, who called data with Merck & Co. Inc.'s twice-daily compound MK-518 the "show stealer" at ICAAC and described trial results as "phenomenal."

In the 10-day study, the drug reduced levels of the virus by at least 98 percent by blocking the enzyme integrase, which HIV needs to survive. About half of the patients showed a virus level of less than 400 copies per milliliter of blood.

"There are whispers of a paradigm shift when it comes to the integrase inhibitors, and I think that's absolutely true," McDonald said. Merck plans to file a new drug application for MK-518 in 2007.

Gilead has an integrase inhibitor, too the oral, once-daily GS 9137 licensed in March from Japan Tobacco Inc. That product began a Phase I/II study in June, with results expected next year. The structure of the compound "you can kind of figure out from the patent," and the drug seems likely to garner efficacy similar to Merck's.

"Truvada plus Sustiva [from BMS] is front line now," McDonald said. "You can see what Gilead's thinking. Why not replace Sustiva with its own integrase inhibitor? Instead of getting two-thirds, they could get the whole pie."

Among others with integrase inhibitor programs is Sunesis Pharmaceuticals Inc., which coincidentally is partnered with Merck in a separate Alzheimer's disease effort.

Also making a stir at ICAAC were two new protease inhibitors for HIV. Tibotec Pharmaceuticals Ltd. said primary 24-week data from the Phase IIb trial of TMC114 in treatment-experienced patients showed that 62 percent of patients won a reduction in viral load of 1 log¹⁰ or more in the highest dose group, compared to 14 percent in the control group. The compound has a "fantastic" profile against resistant HIV, McDonald said. Boehringer Ingelheim GmbH also showed strong data with its protease inhibitor Aptivus (tipranavir), already cleared for marketing in Europe.

Also of interest in the HIV field is Panacos Pharmaceuticals Inc., which this fall raised $86.6 million, largely on the strength of its Phase IIa results with PA-457. The data sent Panacos' stock upward by 45 percent when disclosed in August. The compound deploys a somewhat different mechanism of action by inhibiting newly formed HIV from maturing into infectious virus particles. (See BioWorld Financial Watch, Oct. 20, 2005.)

The Phase IIa study randomized treatment-naïve and treatment-experienced patients to get oral PA-457 in one of four dose levels 25 mg, 50 mg, 100 mg or 200 mg with six patients per group, compared to an eight-patient placebo group for a 10-day treatment period. Viral loads measured at day 11 showed that the two highest doses of PA-457 demonstrated statistical significance vs. placebo, with individual decreases in HIV levels of up to 1.7 log¹⁰. At the 200-mg level, the median viral reduction was greater than 1 log¹⁰, a 90 percent decrease.

The ICAAC poster detailed data from the Phase IIa study, and results from a drug-interaction study are expected near the end of this year or early in 2006, with a Phase IIb study likely to begin in the second half of next year.

Panacos went public this spring after a merger with V.I. Technologies Inc. (known as Vitex). The combined company went as "Vitex," but changed its corporate name to Panacos in August.

McDonald called the Panacos results "interesting" but noted one or two patients who failed to respond despite having high levels of the drug in their blood. Still, "the trend in the study was positive, in that the slope of the curve was continuing to decrease [viral load] with time," he said. "I'd like to see a little more data."

Another poster causing some buzz came from Achillion Pharmaceuticals Inc. (partnered with Gilead on an early stage hepatitis C drug, GS9132, in a potential $110 million deal), which reported on a dose-exploring Phase IIa trial with elvucitabine, an early stage nucleoside reverse transcriptase inhibitor. When given with the protease inhibitor Kaletra (a combination of lopinavir and ritonavir), from Abbott Laboratories, patients won a reduction in viral load with no safety issues like those noted with higher doses of elvucitabine.

Tanox Inc. also offered a poster at ICAAC, which detailed encouraging Phase II data revealed earlier this year from an ongoing trial with TNX-355, the entry inhibitor that could become the first monoclonal antibody available for the disease.

"It'' an intravenous product that has to be given every two to three weeks," McDonald pointed out. "One has to wonder how exactly that will fit in to the treatment paradigm." He allowed that patients who have failed multiple regimens would be "highly motivated" to get the I.V. treatment, but TNX-355 also failed to show an "appreciable increase" in CD4 count, which would have been more pleasing.

Although compounds such as those against methicillin-resistant Staphylococcus aureus infection shared the spotlight at ICAAC, McDonald said HIV was "still the star" of the 45th annual show.

"You've got so many patients living longer now, and correspondingly the number of patients in the third and salvage line is growing, and it's going to keep growing," he said. "Those markets will become even more significant."