Glaxo-Pfizer AIDS Pill May Dislodge Bristol’s, Study Suggests

A drug developed by GlaxoSmithKline Plc and Pfizer Inc. controlled HIV faster and more safely than Bristol-Myers Squibb Co.’s Sustiva in a study, suggesting the experimental medicine may one day be preferred to Bristol’s.

Dolutegravir, a product of Glaxo and Pfizer’s ViiV Healthcare joint venture, reduced HIV to undetectable levels in 90 percent of patients after 48 weeks, compared with 82 percent of those who got Sustiva, according to results presented at an AIDS meeting in Rome today. Dolutegravir also caused a significantly lower rise in bad cholesterol than Sustiva, at one-twelfth of the dose size.

Sustiva is one of three drugs in Gilead Sciences Inc.’s Atripla, the world’s best-selling AIDS pill, and brought New York-based Bristol $1.4 billion in sales last year. Today’s results could signal that dolutegravir may supplant Sustiva, also known as efavirenz, as a preferred treatment in first-line therapy, Michael Saag, director of the Center for AIDS Research at the University of Alabama in Birmingham, said in an e-mail.

“It does raise the possibility of one day replacing efavirenz as the most preferred agent,” Saag said.

The “impressive” results don’t mean dolutegravir has proven it’s superior to Sustiva yet, though that may be shown in a larger study, he said.

Sustiva is recognized by the U.S. Department of Health and Human Services as a component of preferred combination HIV therapy regimens for patients who are new to treatment, said Cristi Barnett, a Bristol-Myers spokeswoman, in an e-mail.

Sustiva’s Data

“While it would be premature for me to speculate on any future treatment guideline changes, Sustiva, as part of combination HIV therapy, has accumulated extensive clinical trial data and clinical experience for more than 12 years,” Barnett said.

The researchers, led by Jan van Lunzen at the University Medical Center Hamburg-Eppendorf in Germany, tested dolutegravir in 205 HIV patients who hadn’t received treatment before. They received one of three doses of either ViiV’s drug or Sustiva once a day for 48 weeks. The doctors involved in the trial could choose whether to combine the treatments either with Gilead’s Truvada or ViiV’s Epzicom.

Dolutegravir reduced HIV to undetectable levels in 92 percent of patients after 16 weeks, compared with 58 percent for a 600-milligram dose of Sustiva. By 48 weeks, 90 percent of those on dolutegravir had undetectable virus, compared with 82 percent of those on Sustiva.

Bad Cholesterol

Patients on dolutegravir, previously known as S/GSK1349572, also got a bigger boost in their CD4 cells -- the immune-system cells HIV infects and kills -- than those on Sustiva, and had a fraction of the rise in bad cholesterol. Some HIV medicines have been linked to an increase in cholesterol, which can lead to heart attacks.

Dolutegravir is in a class of AIDS drugs called integrase inhibitors that work by blocking HIV’s ability to replicate. Data presented at an AIDS meeting in Vienna last year showed dolutegravir was also better at controlling HIV than Merck & Co.’s Isentress, the only approved integrase inhibitor.

“It’s delivering on everything that we’ve asked for it,” said Garrett Nichols, Glaxo’s project leader for dolutegravir, in an interview. Dolutegravir “holds the best promise for long-term treatment success.”

ViiV is now testing dolutegravir in the third and final stage of patient studies usually required for regulatory approval in the U.S. The drug was developed jointly with Osaka, Japan-based Shionogi & Co. It’s also testing the drug with two-drug combination Epzicom as a three-in-one pill against Atripla.

Glaxo owns 85 percent of ViiV and Pfizer owns 15 percent. The two companies split the profits accordingly.

Other Studies

In a separate study, ViiV’s experimental drug lersivirine showed similar efficacy to Sustiva in controlling HIV, with fewer abnormal dreams and dizziness, but with more nausea and headache side effects. The company is now completing the second stage of human trials to get a better understanding of the drug.

“For a new drug to be competitive and offer an advantage over existing therapies it has to have at least equivalent antiviral activity and be better tolerated, or at least as tolerable,” Saag said. “The frequency of nausea in the phase II is key to determining if it should be taken further.” Saag has been a consultant for ViiV and is also a consultant for Bristol and Gilead, he said.

A third trial tested an older ViiV pill, Selzentry, against Gilead’s two-drug combination Truvada, when both were added to Bristol’s Reyataz and Abbott Laboratories’s Norvir. Over 48 weeks, Selzentry lowered HIV to undetectable levels in 75 percent of patients, compared with 84 percent of those on Truvada.

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