Gilead Sciences had some great news at the end of last week after US regulators backed two drugs from its HIV portfolio - Truvada for reducing the risk of contracting the disease and its four-in-one Quad pill to treat it.
First up, in what some consider to be a controversial decision, the Antiviral Drugs Advisory Committee of the US Food and Drug Administration has voted in favour of approving Gilead's once-daily pill Truvada (emtricitabine and tenofovir disoproxil fumarate) to reduce the risk of HIV-1 infection among uninfected adults.
Members of the panel voted: 19 to 3 in favor of approving Truvada for pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM); 19 to 2 in support of its use in HIV-uninfected partners in serodiscordant couples; and 12 to 8 in others at risk of contracting HIV through sexual activity.
The positive recommendation comes on the back of data from several clinical studies showing the use of Truvada for PrEP to be safe and effective, including the 2,499 subject iPrEx study, in which a group of MSM taking PrEP Truvada had 43% fewer infections than those taking a placebo.
Truvada was first approved by the FDA in 2004 for the treatment of HIV-1 infection, and is currently the most-prescribed antiretroviral treatment in the US. If regulators give the drug the OK in the PrEP setting, it will be the first agent indicated for uninfected individuals to cut their risk of acquiring HIV.
But opinion over its use for PrEP is divided. In march this year, the AIDS Healthcare Foundation (AHF) filed a citizen’s petition with the FDA asking it to "delay or deny" approval of Gilead's additional marketing approval for Truvada for PrEP.
It argues that such a use would actually increase HIV infections, and notes that recent research has linked one of the components of Truvada - tenofovir - to a significant risk of kidney disease and damage.
"The idea of giving healthy people a toxic drug that will damage their kidneys in order to possibly prevent HIV – when simple condom use is 95% effective – is the height of irresponsibility and corporate greed,” said Michael Weinstein, AHF’s president, and added that “widespread use of PrEP has all the makings of a public health disaster – increased HIV infections, drug resistant strains of HIV, and tens of thousands of damaged kidneys".
And according to global business intelligence provider GlobalData, a number of other experts have expressed serious concerns regarding the use of Truvada as PrEP.
In particular, there are fears over whether at-risk patients will stop using other preventative methods like condoms, and, as the drug's efficacy depends on consistent daily administration, "there is concern that non-adherence will fail to prevent HIV transmission in people who would otherwise use a condom during sex".
Also, it says opponents are worried that treating HIV-naive patients with Truvada could foster the evolution of a drug-resistant HIV strain, making it even more difficult to treat and control.
Nevertheless, GlobalData anticipates that the FDA will approve Truvada for all three PrEP indications, and that this could "significantly increase" sales of the drug, which came in at $2.88 million last year, given that the Centre for Disease Control estimates that 415,000 in the US alone are at high risk for contracting HIV.
Support for the Quad
Meantime, an advisory committee has voted 13 to 1 in support of providing marketing clearance of the Quad - Gilead's single pill regimen containing elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate - for the treatment of HIV-1 infection in treatment-naive adults.
The Quad's application is supported by the positive results from two pivotal Phase III studies, demonstrating that the pill is non-inferior to the firm's own big selling combo Atripla (efavirenz/tenofovir/emtricitabine) after 48 weeks of therapy.
At the end of the trial, 88% of patients who took Quad had achieved HIV RNA levels (viral load) of less than 50 copies/ml, ie no detectable levels of HIV in their blood, compared with 84% for those on Atripla.
In addition, Gilead said the studies showed its product to be well tolerated, with adverse events mild-to-moderate in the main, including nausea, upper respiratory track infection and headache.
Marketing applications for the Quad have also been filed in Australia, Canada and the European Union.