A medical landmark that might call for fanfare -- a second drug to prevent HIV infection -- is receiving boos from HIV/AIDS advocates who say its rollout could be a step backward, not forward, in access to HIV prevention. In early October, the U.S. Food and Drug Administration (FDA) approved Descovy (emtricitabine/tenofovir alafenamide), manufactured by Gilead Sciences, for men who have sex with men and transgender women as a daily pill for pre-exposure prophylaxis, or PrEP. But the drug isn't approved for vaginal sex -- the company didn't test for it -- and that ignores a crucial at-risk part of the population, critics say. Gilead has been touting Descovy's safety -- inflating its safety, detractors say -- to convert patients from the older PrEP formula, Truvada (FTC/tenofovir disoproxil fumarate), which will lose patent protection next September and face an onslaught of cheaper generics. The potential problem with that switchover, critics say, is that it will boost the company's bottom line more than it will improve public health and safety.
Descovy, one of Gilead's tenofovir alafenamide (TAF)–based meds, was approved in 2016 to treat people living with HIV before its approval for PrEP. It is technically not a new drug, but rather a reformulation of Gilead's older medication, Truvada, which has been used to treat people living with HIV since 2004. Truvada, approved as a daily pill for PrEP in 2012, is recommended for on-demand use, also called 2-1-1 dosing, by many HIV advocates and some municipal health departments -- though, like Descovy for daily use, not for cis women or trans men.
Descovy's FDA approval does not outline a plan for making the drug available to women who have vaginal intercourse, though the agency did put out a statement that Gilead agreed to conduct studies for the drug’s effectiveness for protection against HIV in the vagina. The DISCOVER trial only tested Descovy's efficacy regarding anal sex. Some activists and scientists said the approval sets a dangerous precedent by allowing companies to dodge the expensive trials needed to test medicines in women.
In an email, a spokesperson for Gilead explained the company's exclusion of cisgender women in trials: "Because of the variable results seen previously with Truvada for PrEP in large clinical trials in ciswomen, we and the FDA were unable to align on an appropriate or feasible design for a phase 3 trial in ciswomen." The email continued, saying Gilead is now "committed to generating data in women and we have agreed with FDA on the framework of a novel trial design to assess Descovy for PrEP in ciswomen. A protocol will be complete by early 2020, and the trial will be conducted soon thereafter."
In an email, Sybil Miller, communications manager for SisterLove, Inc., said the lack of safety and effectiveness testing in cisgender women is a barrier to PrEP access. Miller said she would like to see greater knowledge and awareness of and for black women about both Truvada and Descovy, as well as a guideline for PrEP that doesn't skew "bias" against prescribing to most women. "Less than 10% of PrEP users are cisgender women, and most of them are not African American," Miller told TheBody. "Although there is a disconnect, there's also room for opportunity for education and dialogue on the topic."
Jim Pickett, senior director of prevention and advocacy for gay man's health at AIDS Foundation of Chicago, was more blunt, saying there is no excuse for Gilead to exclude cisgender women. "It's BS that the tests are too complex to recruit women. Every trial is complex. [Gilead] didn't want to spend the money, because their market for full-price Descovy is in the U.S. and it's mostly men."
In a statement following the FDA approval of Descovy, Treatment Action Group (TAG) slammed Gilead's "entirely inadequate engagement with community previously as part of the phase III Discover trial that led to such an inequitable FDA approval."
And it criticized the company's messaging around Descovy: "TAG also calls on Gilead to stick to the evidence, and immediately cease all messaging claiming that F/TAF is safer or more effective than its current marketed PrEP product TDF/FTC (Truvada), which will go off patent in 2020. In an effort to maintain its $2 billion in domestic PrEP profits, the company appears to be desperately trying to switch patients over to F/TAF by misrepresenting TDF/FTC. In fact, while the Discover trial showed minor improvements in bone density and renal health indicators in F/TAF compared to TDF/FTC, it has a worse obesity and cardiovascular risk profile than TDF/FTC. Particularly in light of F/TAF's narrow indication as PrEP, it is essential for all to know that TDF/FTC is a safe and effective option for PrEP."
Elaborating on the statement regarding Gilead's misrepresentation of Descovy, Jeremiah Johnson, TAG's HIV director, said that legally the company can only say that Descovy is not inferior to Truvada and that the company announced the non-inferiority of Descovy.
"But in slides in presentations, Gilead has clearly said Descovy is safer," Johnson says. The bottom line, Johnson claims, is that Gilead has been laying the groundwork to switch over to Descovy right before Truvada goes off patent, based on spurious claims. "For 10 years, the company worked with communities saying Truvada is safer than aspirin, [but now] they are expressing concerns about its safety," he said.
"We're worried that people will be deterred from using Truvada when Descovy won't necessarily be better," Johnson continued. "And private insurers will create hurdles to prevent you from going on the expensive meds, and if people fear using Truvada and can't afford Descovy or don't know about patient assistance, they might not use any meds at all. At a time we're hoping to fill the gaps in a broken health care system, we have to contend with messaging that may exacerbate the problem."
Gilead said that the list price for both Truvada and Descovy is $1,758 per month. It also said it has several patient assistance programs in place to help people access Descovy.
In a statement, Gilead disputed claims that it had misrepresented the safety of Descovy, saying that in presentations on the results of the DISCOVER trial -- at the Conference on Retroviruses and Opportunistic Infections (CROI), sharing additional results at the International AIDS Society Conference on HIV Science, and at the IDWeek conference -- the company "clearly stated that the efficacy of Descovy is non-inferior to Truvada for the prevention of HIV."
"In addition, all of the claims featured in Gilead's promotional materials are consistent with the results of the DISCOVER trial and approved product labeling, and all trial data presentations in the materials clearly state the non-inferior efficacy outcome," the statement read.
Still, advocates are concerned that doctors and patients will think that Descovy is replacing Truvada because it's safer. Part of that worry comes from the class-action suit involving 140 patients in 31 states accusing Gilead of promoting drugs the company knew led to bone and kidney damage in patients. The lawsuit claims the company's switch to the newer drug depended on "the very benefits that Gilead could have and should have incorporated into its prior product designs but withheld from doctors and patients for over a decade."
Pickett said the lawsuits over Truvada's safety could, in a roundabout way, help the company launch Descovy at the expense of the older drug. "The lawsuits have been scaring people and leading them to go off Truvada," Pickett said.
Pickett brings up one possible side effect to the Descovy rollout, involving medical centers participating in the 340B drug discount program, which requires drug manufacturers to provide outpatient drugs to eligible health care organizations at significantly reduced prices.
"Right now, centers that participate [in 340B] can buy name brand drugs at a significant discount for their Medicaid clients, save the difference, and put that money back into other services. In order to get that deep discount once the huge rebates for Truvada stop when it goes generic, what are [340B programs] likely to do? They'll prescribe the expensive drug, Descovy. But they will only be prescribing it to get the money back, not because Descovy is better. It's a perverse incentive that says volumes about the [health care and pharmaceutical] system, and Gilead is responsible for the mess we're in."