Nature Medicine | Spoonful of Medicine

Gilead under pressure to produce stand-alone version of new HIV drug

TAF_TDF

National AIDS Treatment Advocacy Project

In 2001, the US Food and Drug Administration approved a new HIV medication called tenofovir disoproxil fumarate (TDF). Patient advocates hailed the decision, noting that it represented the first novel antiviral agent to get the green light after the FDA turned down a similar drug  two years earlier. But a lot changes in a decade. For one thing, the maker of TDF, Gilead Sciences of Foster City, California, has a newer, better formulation of tenofovir, called tenofovir alafenamide (TAF). Meanwhile, patient advocates at the International AIDS Society Conference in Kuala Lumpur this week are crying foul that the company isn’t working on a stand-alone version of TAF and plans to sell it only in expensive combination pills.

Currently, TDF is available from Gilead as a solo formulation (sold as Viread). It’s also available as part of Stribild, a fixed-drug combination ‘quad’ pill that also includes the drugs elvitegravir, cobicistat and emtricitabine—the four drugs designated for first-line treatment by the World Health Organization. TAF is currently in development as part of three different combination pills: as a dual-drug tablet with emtricitabine; and in two different combination pills, one of which uses TAF as a substitute for TDF in the currently available ‘quad’ pill, and then in another new single-pill treatment which contains darunavir, cobicistat, and emtricitabine.

Without a stand-alone version of TAF, health programs in poorer parts of the world cannot combine it with cheaper alternatives, such as lamivudine, which works like emtricitabine but, at $37 for a year of treatment, costs about half as much.

A letter, which carried almost 300 signatures from advocates around the world—including those from groups such as the New York-based Treatment Action Group, HIV i-Base in the UK and San Francisco’s Project Inform—was sent on 13 June to Gilead Sciences pleading the case for TAF development as a stand-alone drug.

“In the US, keeping TAF bundled with other brand-name agents would likely curtail our ability to benefit from TAF’s potential improved safety in combination with generic agents to reduce annual treatment costs,” says Tim Horn, HIV project director for the Treatment Action Group.

A stand-alone version of TAF would also make it possible for generic versions of the drug to perhaps become available—a huge boon in particular for populations in resource-limited countries—if Gilead eventually decides to license TAF with the Medicines Patent Pool, as it did with TDF in 2011.

An upgrade

A lot is at stake. Both TDF and TAF are what are known as nucleotide reverse transcriptase inhibitors (NRTIs), which slow the replication of HIV inside immune cells. But preliminary research suggests that the latter is a substantial upgrade. Studies show that 25 milligrams of TAF outperformed 300 milligrams of TDF—achieving seven times the tissue concentration of TDF— when tested in the four-drug ‘quad’ combo. TAF also had fewer side effects on kidney function and bone density. Even more promising, recent research shows TAF may work against HIV strains resistant to TDF and other NRTIs.

When reached for comment, Cara Miller, a spokesperson for Gilead, told Nature Medicine that the development of new single-tablet HIV regimens, including those containing TAF, is a priority for the company. However, solo-drug formulations of TAF only appear in the company’s drug development pipeline for phase 1 studies on chronic hepatitis B virus infections. Miller didn’t have any further information about TAF development at this time.

“We want there to be a fixed-dose combination because it helps people with compliance,” says Kate Krauss, executive director of the AIDS Policy Project in Philadelphia. “But, if the only thing available is a patented fixed-drug combination, the high price will put it out of reach for millions of people.”

“Other lifesaving AIDS drug combinations that could be created using a brand name Gilead drug and cheaper generics will not be possible,” Krauss adds. “When patients run out of drug combinations that work, they run out of time.”

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