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Glaxo, Shionogi Say HIV Drug Beats Gilead Atripla in Test
  Bloomberg. By Makiko Kitamura and Simeon Bennett - Jul 15, 2012 7:01 PM ET

GlaxoSmithKline Plc (GSK) marketed the first HIV drug a quarter century ago before losing out to Gilead Sciences Inc. (GILD) as the world's biggest maker of AIDS medicines. Now Glaxo is staging a comeback.

Glaxo's HIV-focused joint venture with Pfizer Inc. (PFE), ViiV Healthcare Ltd., has produced the first drug to beat Gilead's top-selling Atripla pill in a study. The experimental dolutegravir medicine, combined with ViiV's older two-in-one treatment Epzicom, reduced the virus to undetectable levels in more people than the three-in-one Atripla, with fewer side effects, ViiV said last week.

Together with a previous trial that showed dolutegravir works better than Merck & Co. (MRK)'s Isentress, the results suggest the pill may become a preferred first option for HIV treatment, adding as much as $2.8 billion to sales and raising the likelihood that ViiV will sell shares in an initial public offering, according to Deutsche Bank AG. While that possibility has been raised since ViiV's inception in 2009, an IPO isn't management's priority, said Dominique Limet, ViiV's chief executive officer.

"My ambition is to rebuild a very well-known and recognized company specializing in HIV and AIDS," Limet said in an interview at ViiV's headquarters in Brentford, England, just outside London. "After a period of setbacks in terms of R&D and decline of our sales, with a forthcoming pipeline of products, we can re-energize the sales momentum."

Drug Combinations

Glaxo developed the first drug against HIV, Retrovir, in 1987. The virus became resistant to the treatment when given on its own, leading to the development of therapeutic cocktails consisting of three medicines that stop HIV from replicating, curbing its attack on the body's immune system.

Atripla, which earned Foster City, California-based Gilead $3.2 billion in sales last year, was the first treatment to pack three HIV drugs into a single pill, taken once daily. It combines Gilead's two-in-one drug Truvada with a third medicine called Sustiva from New York-based Bristol-Myers Squibb Co. (BMY)

Now ViiV's studies are spurring doctors and Limet to consider which combinations of drugs will work best for patients. While ViiV is formulating a single pill that combines dolutegravir with Epzicom, it is exploring other combinations, Limet said.

'The Beginning'

"It's just the beginning of the journey," he said. A major focus for ViiV is to "reduce the burden of not only the disease but the burden of treatment schemes."

Doctors cite concerns for side effects that plague both ViiV's Epzicom and Gilead's competing Truvada, which is included in Atripla as well as its forthcoming Quad pill.

A study published in The Lancet medical journal in 2008 found abacavir, a component of Epzicom, was associated with an increased risk of heart attack in HIV patients. The U.S. Food and Drug Administration last year said it analyzed 26 clinical trials on abacavir conducted between 1996 and 2010 and concluded that taking the drug isn't linked to heart attack risk.

Still, there remains a prejudice against abacavir, especially among doctors in the U.S., as some haven't tracked all of the follow-up studies showing the drug's safety, said Jeffrey Laurence, senior scientific consultant at the New York- based Foundation for AIDS Research and professor at Weill Cornell Medical College.

"That initial study made a huge splash," he said.

Side Effects

Gilead's Truvada, for its part, contains tenofovir, which may cause kidney damage or bone loss, according to the drug's prescribing information.

"It's a bit like football teams: some support abacavir, some hate abacavir, some support tenofovir, some hate tenofovir," said Mark Nelson, a consultant HIV physician at Chelsea and Westminster Hospital in London.

Doctors may consider prescribing dolutegravir with Truvada, which is the basis of the four first-line treatment regimens in the U.S recommended by the Department of Health and Human Services, said Paul Sax, an HIV physician and a clinical director at Brigham and Women's Hospital in Boston. That combination also enables patients to avoid the exhausting nightmares that accompany taking Sustiva, which is contained in Gilead's Atripla pill, he said.

In ViiV's study comparing dolutegravir with Isentress, dubbed Spring-2, participants in both treatment groups took either Truvada or Epzicom as the backbone medicine. More details on side effects and efficacy will be presented at the International AIDS Conference in Washington starting this weekend.

Changing Perception

"The combination with Truvada will get a very close look," Sax said. "A lot of the patients in that study, we can expect, took Truvada with dolutegravir, and it would not surprise me at all if that group does extremely well, and has fewer safety concerns, at least up front, than abacavir."

Epzicom is more widely accepted in Europe, where it's marketed as Kivexa, and "I feel very confident that over time, we will be able to see a change everywhere in the world in regards to perception," Limet said. "We have accumulated such a body of evidence, and that's what the FDA has recognized."

Still, doctors will have the option to prescribe dolutegravir on its own with any other approved drugs, he said. While single-pill combination drugs are convenient for patients, "it's important that physicians not trade potential side effects for the sake of simplicity."

Bone Density

Garry Brough, who was diagnosed with HIV in 1991, has taken both abacavir- and tenofovir-containing treatments. After seven years on the abacavir-based therapy, he switched to the other while being treated for hepatitis C, as recommended by his doctor.

Two years later, he said he was diagnosed with low bone density, an early warning sign for potential osteoporosis. That prompted him to switch back.

"I'm very happy with the treatment," said Brough, 45, a membership involvement officer at patient advocacy group Terrence Higgins Trust in London. "I'm not worried about my cardiovascular risk. But reduced bone density? I didn't like that one as much."

ViiV, with 1.57 billion pounds ($2.44 billion) in annual sales in 2011, is awaiting results from two more studies on dolutegravir for treatment-resistant patients that will be released by the end of the year. The company will probably file for regulatory approval early in 2013, Limet said.

Sharing Sales

The company's partner is Osaka, Japan-based Shionogi & Co. (4507), which will take half the earnings from sales of dolutegravir. As Glaxo owns 85 percent of ViiV, it will take 42.5 percent of profit from the drug and New York-based Pfizer will receive 7.5 percent.

Shionogi established its European headquarters in London in February to market dolutegravir in the region.

In addition to developing treatments for HIV, ViiV is also working on medicines to restore the body's immune system while on treatment and also a potential cure for AIDS, which may materialize by 2025, Limet said. The latter project will require partnerships with academic institutions and other drugmakers, he said.

"Our employees went through a number of setbacks and disappointments," Limet said. "And they were so resilient, so adamant to demonstrate that some of the statements were possibly overstated, about side effects, about the fact that we were no longer leading the HIV fight." With dolutegravir, "a new hope has emerged in our team."

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