New HIV Drugs Grab the Spotlight

Offerings by Gilead and Merck have rightfully garnered a lot of recent attention.
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The curtain has closed on the big HIV research meeting in Los Angeles, with new "integrase inhibitor" drugs from

Gilead Sciences

(GILD) - Get Report

and

Merck

(MRK) - Get Report

garnering much of the spotlight.

These new drugs represent a promising

novel class of therapies for HIV patients, especially for those with a virus that has mutated and become resistant to currently marketed HIV drugs.

Unlike existing HIV drugs, the new drugs from Gilead and Merck work by blocking integrase, an enzyme that helps the HIV virus merge its genetic material with that of a patient's host cell.

On the surface, the efficacy of Merck's drug, raltegravir, looked better than Gilead Sciences' drug, known as GS9137. This may account for some of the weakness seen last week in Gilead shares (in addition to the big downturn in the overall market.)

Gilead closed Friday at $70.44, losing 4.3% for the week. Merck closed Friday up 20 cents to $44.19.

But for important reasons that I'll detail below, it's difficult to make head-to-head comparisons between the two drugs. In fact, both drugs showed strong efficacy with clean safety profiles. Merck expects to seek FDA approval for raltegravir in the second quarter; while Gilead will start phase III studies of GS9137 by the middle of the year.

I put together a chart of the major data highlights from both drugs, which was presented at the annual meeting of the Conference on Retrovirus and Opportunistic Infections last week.

From an efficacy standpoint, the most stringent measure is the percent of patients achieving viral load less than 50 copies. It's at this point that HIV patients are deemed to have undetectable virus in their systems.

A glance at the chart shows that 61% and 62% of raltegravir patients achieved undetectable status compared with 44% and 36% in the controls arms of the two phase III studies.

Merck

Gilead Sciences

Raltegravir Benchmark 1

control

Raltegravir Benchmark 2

control

GS9137 phase IIB 125 mg

control

baseline HIV RNA (log)

4.6

4.5

4.7

4.7

4.7

4.54

baseline CD4 cell count

156

153

146

163

157

158

Efficacy

Time (weeks)

16

16

16

16

16

16

Mean viral load reduction

1.7

1.2

% less than 400 copies

77%

41%

77%

43%

% less than 50 copies

61%

44%

62%

36%

40%

30%

increase CD4 cells

83

31

86

40

61

28

In Gilead's study, 40% of GS9137 patients on the highest dose had undetectable virus compared with 30% of control patients.

What the chart doesn't tell you, however, is that patients in Merck's study had less-advanced disease and were less heavily pretreated with other HIV drugs than those enrolled in Gilead's study. For instance, 25% of HIV patients enrolled in the raltegravir studies had virus that was resistant to all currently marketed drugs. For the Gilead study, 48% of patients taking GS9137 were resistant to all drugs.

Furthermore, the Merck studies allowed potent protease inhibitors drugs to be included in the background regimen that all patients received in addition to raltegravir. But in the Gilead study, protease inhibitors were only allowed in the control arm at first, which put GS9137 patients at a clinical disadvantage. It was only partway through the trial that GS9137 patients were allowed to start taking protease inhibitors as well.

That's not to take anything away from Merck's drug, because it showed impressive efficacy, but the phase III studies were somewhat optimized to get the best results. The Gilead study, however, set up a more difficult challenge for GS9137. Viewed through that lens, the drug's efficacy still came through strongly.

Once approved, integrase inhibitors will likely be used in treatment-experienced HIV patients, although the drugs' clean safety profile could lead some doctors to use them off-label in newly diagnosed patients. Merck's raltegravir has a good 18-month lead on Gilead's drug, but once approved, raltegravir will likely be most used in combination with Gilead's top-selling HIV treatment backbone, Truvada.

Current HIV drugs most at risk for being shunted aside by the use of integrase inhibitors include the NNRTI class of drugs, such as

GlaxoSmithKline's

(GSK) - Get Report

Sustiva, and some older protease inhibitors, including

Abbott Labs'

(ABT) - Get Report

Kaletra.

Fuzeon, marketed by

Roche

and

Trimeris

(TRMS)

, also faces considerable headwind from new HIV drugs because Fuzeon must be given by injection and causes significant, painful side effects.

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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