GSK focuses on two-drug HIV treatment

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GlaxoSmithKline is pinning the future of its HIV business on an audacious bet: that their latest HIV pill is powerful enough to suppress the virus with the help of just one other drug, reports The Wall Street Journal.

The treatment of HIV, the virus that causes Aids, has changed little since the mid-1990s, when the introduction of a new class of drug dramatically improved HIV therapy. Doctors found that combining the newer type of antiretroviral drug with two drugs from an earlier class hindered the virus from developing resistance.

A three-drug regimen has remained the standard approach since then, with drug development efforts focused on making ever more powerful triple combinations. The report says Glaxo executives want to change that. They hope the UK-based drug company’s latest HIV pill is powerful enough to suppress the virus with the help of just one other drug. That, according to CEO Andrew Witty, would be a “game-changer,” because taking fewer drugs would produce fewer side effects.

Now, Glaxo’s majority-owned HIV business ViiV Healthcare is getting down to the long process of proving it.

The report says the drug in question, dolutegravir, is one of a class of HIV drugs known as integrase inhibitors that rapidly reduce the level of virus in the blood. It is already approved for use as part of traditional triple therapy and so far, there are no reported cases of the virus developing resistance to dolutegravir in patients who are new to treatment. That makes it unique among integrase inhibitors, according to David Hardy, an HIV doctor and a spokesperson for the HIV Medicines Association, an advocacy group.

While dolutegravir’s profile suggests it could potentially suppress HIV without the help of any other drug, Glaxo is taking a precautionary stepwise approach to investigating its promise, said a company spokesperson in the report.

The most important benefit of a two-drug regimen is that it would come with fewer side effects. Such effects, including nausea, diarrhoea, kidney problems and bone-thinning, are one of the most common reasons for patients to change an HIV regimen. It could also lighten the financial burden of HIV.

Rochelle Walensky, associate professor of medicine at Harvard Medical School, estimated that switching just a quarter of patients currently on triple therapy to dolutegravir plus 3TC – an older, generic HIV drug – would knock more than $3bn off the cost of treating HIV over a five-year period. The cost saving is less clear if both drugs in the regimen are still under patent protection.

Glaxo is putting “tremendous focus and priority” on the development of two-drug regimens, Witty said. According to analysis by UBS, the opportunity is significant: If dual therapy becomes the strategy that doctors prefer, Glaxo could grab a much bigger slice of the market and overtake Gilead Sciences to become the biggest player in HIV treatment within three years.

The report says over the past year, Glaxo has started several large clinical trials that aim to show that combining dolutegravir with just one other HIV medicine works as well as traditional triple therapy at suppressing the virus. In one set of trials, it is testing dolutegravir alongside rilpivirine, a brand-name HIV drug made by Johnson & Johnson unit Janssen Pharmaceuticals. In another, it is combining dolutegravir with 3TC, the generic drug used in Walensky’s analysis.

It also plans to start a late-stage trial combining an injectable version of dolutegravir with rilpivirine, the report says. An earlier trial showed this combination was as effective as a three-drug regimen when the virus had already been suppressed by an initial period of triple therapy.

The trials won’t start yielding results until next year, but, the report says, a small study led by Pedro Cahn, a doctor in Argentina, offers some reason for optimism. In that 48-week trial, dolutegravir plus 3TC suppressed HIV levels in 18 out of 20 previously untreated patients.

But, the report notes, even if Glaxo’s large clinical trials succeed, it could face another challenge: inertia. In the past year, Gilead has launched a series of triple therapies using a new HIV drug called TAF that can be administered at a much lower dose than its predecessor, causing less harm to the kidneys.

Christoph Wyen, an HIV specialist at the University Hospital Cologne in Germany, said the advent of these less-toxic triple therapies reduces the incentive for doctors to switch patients to simpler regimens. He said dual therapy might take off more quickly in older patients, who are more likely to have age-related health complications.

The report says Gilead and Glaxo both have strong positions in the HIV market with TAF- and dolutegravir-based triple regimens, respectively. But Gilead is developing a new integrase inhibitor that, if proven equal to dolutegravir, could give it an important advantage in the triple-therapy market.

The worst-case scenario for Glaxo would be for its dual therapies to fail and for Gilead’s integrase inhibitor – which, if successful, is expected to launch in 2018 – to steal market share from dolutegravir. That, the report says, could send Glaxo’s HIV business into decline after 2018, according to UBS, though Witty says that the downside is limited because dolutegravir will be well-established by the time Gilead’s competitor comes along.

“It’s not a foregone conclusion that (dual therapy0 is going to work,” said Hardy is quoted in the report as saying. But “I’ve watched the development of dolutegravir enough to understand why they are trying to do this.”

The Wall Street Journal report

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