Merck-Gilead Drug Duel Is Heating Up - TheStreet

A couple of experimental drugs designed to fight HIV in new ways will highlight an important and closely watched medical meeting next week.

Drugmakers

Merck

(MRK) - Get Report

and

Gilead Sciences

(GILD) - Get Report

are expected to present new clinical data at the annual Conference on Retroviruses and Opportunistic Infections, Feb. 25-28 in Los Angeles.

The CROI meeting brings together scientists and researchers from around the world and is generally viewed as one of the most important forums for the presentation of new HIV drug research. CROI is also a bit unique in that it bars entry to anyone connected to Wall Street, including sell-side analysts and fund managers. Even the financial press -- myself included -- isn't allowed to attend.

I may need to watch from the outside, but I'll still be covering the data duel between Merck and Gilead, both of which are developing similar HIV drugs known as integrase inhibitors. Merck is in the lead with about a 12-month time advantage over Gilead. But in HIV treatment, speed and being first to market don't guarantee victory.

The Hows of HIV

To understand why, start with a short lesson in the science behind HIV: In order for HIV (human immunodeficiency virus) to successfully replicate itself, the virus must first infect a host cell and integrate itself into the cell's genome. Three enzymes in the body help the virus accomplish this task: reverse transcriptase, protease and integrase. Once HIV gets cozy inside a host cell, it turns that cell into an HIV factory, capable of churning out new copies of the virus to seek out and infect new cells.

There are currently three major classes of antiretroviral drugs used to treat HIV. Two of these classes work by inhibiting the action of the reverse transcriptase enzyme; the third class inhibits the protease enzyme. Modern HIV therapy, which involves patients taking a cocktail of these drugs, does a remarkable job of tamping down the virus to undetectable levels. HIV and AIDS (acquired immune deficiency syndrome) used to kill patients quickly but now have been somewhat defanged, and HIV infection is treated more like a chronic disease. (There is still no "cure" for HIV because under current therapies, the virus is never 100% eliminated from the body.)

The problem, however, is that HIV is a smart virus and over time can mutate into forms that are resistant to existing drugs. That's why the development of new classes of HIV drugs that fight the virus in novel ways is important.

Drug Details

To that end, Merck and Gilead have developed drugs that fight HIV by inhibiting integrase. Specifically, integrase is the enzyme responsible for allowing viral DNA to enter the nucleus of the host cell and integrate into the host cell genome. Clinical data presented so far by both companies have excited HIV researchers because integrase inhibitors appear to be very effective in fighting the virus with fewer side effects than current HIV medicines.

Merck's drug goes by the name MK0518. At the CROI meeting, Merck will present for the first time clinical data from two phase III studies testing MK0158 in combination with other HIV drugs in treatment-experienced HIV patients. Said another way, these are patients in whom the virus has developed resistance to certain current HIV drugs.

Merck has already announced plans to seek approval of MK0158 with the Food and Drug Administration in the middle of the year. MK0518 could be approved and on the market by early next year, if Merck proceeds on plan.

Gilead's integrase inhibitor is called GS 9137. At CROI, data will be presented from a phase IIb study of GS 9137, also in treatment-experienced HIV patients. Gilead has already stated that it will start phase III studies of GS 9137 in mid-2007. If so, data should be available in mid-2008 and the drug could be approved in early 2009.

As in all HIV drug studies, the efficacy of both integrase inhibitors will be measured by the reduction in viral load. The gold standard is the percentage of patients who reach the detection limit of less than 50 copies per millileter. Such patients are deemed to have "undetectable" viral loads. Because current HIV treatment regimens get patients to undetectable levels, the safety profile of new HIV drugs is also very important, if not more important.

In Merck's phase IIb study, previously announced, between 57% and 67% of patients taking MK0518 were able to reduce their viral load to undetectable levels, compared with 14% of placebo patients. For the most part, this is the efficacy standard with which Gilead's GS 9137 will be compared when its data are presented next week. (Some differences in the design and conduct of the Gilead study will make comparison difficult.)

On the safety side, both drugs have looked relatively clean, although a handful of patients in previous MK0158 studies developed potential liver toxicity while on the drug. Any signal of future problems with liver toxicity with be carefully scrutinized in the Merck data to be presented next week.

Apart from that, the major difference between the two drugs is the way they are administered. Merck's MK0518 is taken twice daily; Gilead's GS9137 is taken once a day, although it must be given with a 100 milligram dose of ritonavir, another HIV drug that helps boost the therapeutic effect.

The race to get the first integrase inhibitor approved is not a winner-take-all game. As I said, safety and tolerability of the drugs is just as important as efficacy. And while Merck's drug now appears headed toward first approval and sale, doctors will be most likely to prescribe it to patients in combination with Gilead's core HIV regimen, Truvada. (Merck's phase III studies of MK0518 use Gilead's Truvada as the backbone regimen for patients.)

And because GS 9137 is a once-daily pill, Gilead could co-formulate it with Truvada to create a single-pill therapy. Gilead did just that recently with Atripla, which combines Truvada with the

Bristol-Myers Squibb

(BMY) - Get Report

drug Sustiva. Generally speaking, HIV patients prefer once-daily treatment regimens.

Below is a chart, recreated in part from a Jefferies & Co. report, that compares the drugs from Merck and Gilead Sciences:

As originally published, this story contained an error. Please see

Corrections and Clarifications.

Adam Feuerstein writes regularly for RealMoney.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;

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