GlaxoSmithKline's HIV PrEP challenge looms as ViiV's long-acting drug tops Gilead's Truvada in women

GlaxoSmithKline’s ViiV Healthcare unit has been hoping to launch its PrEP challenger to simultaneously help both men and women prevent HIV. But that plan depended on very optimistic expectations for results from a head-to-head clinical trial against Gilead Sciences' Truvada in women. Now, it has those data.

ViiV’s injectable cabotegravir, given every two months, was 89% more effective at preventing HIV in cisgender women than daily oral Truvada, which is the current standard of care, according to data from the HPTN 084 study, the company revealed Monday.

The landslide clinical win in women came about a year ahead of schedule: After analyzing interim results, an independent data monitoring board recommended stopping the blinded phase of the trial and offering the ViiV injectable to the trial’s Truvada recipients.

It also came just a few months after cabotegravir topped Truvada at preventing HIV among men and transgender women in the HPTN 083 trial. Both studies were run by the National Institute of Allergy and Infectious Diseases under its HIV Prevention Trials Network (HPTN).

“With the combined landmark findings of HPTN 084 announced today and HPTN 083 announced earlier this year, we’ve confirmed that long-acting cabotegravir is a superior HIV prevention option for men and women,” Myron Cohen, M.D., co-principal investigator of the HPTN, said in a statement.

ViiV’s been aiming to file cabotegravir for FDA approval in the first half of 2021 and potentially launch in the first quarter of 2022, ViiV CEO Deborah Waterhouse said in an interview in October. The only moving part to that plan was whether HPTN 084 could read out in time to support its use in women.

RELATED: GSK's ViiV, touting superior long-acting data, can challenge Gilead in HIV prevention: analyst

HPTN 084 enrolled more than 3,200 participants across seven countries in sub-Saharan Africa. At the interim analysis, 38 women in the study had acquired HIV. Among them, four belonged to the cabotegravir arm and 34 received Truvada. This translated into an HIV infection rate of 0.21% for the ViiV injectable and 1.79% for Truvada.

As for HPTN 083, which enrolled 4,600 subjects, cabotegravir slashed HIV acquisition by 66% compared with Truvada, with a lower infection rate of 0.38%, versus the Truvada group’s 1.21%, according to data unveiled at the virtual International AIDS Conference in July.

Participants’ nonadherence to daily Truvada likely tipped the results in cabotegravir’s favor. But the convenience of reducing dosing to just six times a year from 365 is part of the ViiV med’s inherent appeal.

And still, ViiV said Truvada adherence appeared to be higher in this study than in previous HIV prevention trials. Preliminary assessment in a random subset of 362 HPTN 084 participants showed detectable tenofovir—one of two active ingredients in Truvada—in 64% of women, and 48% of all samples tested showed daily dosing levels. Tenofovir was found in 87% men in HPTN 083. Previous studies have suggested that women need better adherence than men for Truvada to work properly, probably because of differing drug concentrations in genital tissues.

Cabotegravir, if eventually approved, could pose another serious threat to Gilead, which is already facing generic Truvada; Teva launched its copycat version in October. During the company’s third-quarter call a few days ago, Gilead’s chief commercial officer, Johanna Mercier, warned investors to brace for a significant Truvada sales decline in the fourth quarter.

Gilead already has a countermeasure in Descovy. Approved by the FDA in PrEP last fall, Descovy uses a different version of tenofovir that carries lower risks of bone and kidney side effects. As of Q3, Gilead has successfully converted 46% of Truvada takers to Descovy, ahead of the company’s previously stated goal of up to 45%.

RELATED: Gilead's Truvada faces Teva generics assault amid Descovy switching campaign

As ViiV’s Waterhouse sees it, that kind of conversion rate bodes well for cabotegravir as it shows “there’s a willingness to switch even to a non-inferior product that has some side effect benefit.” Cabotegravir, with its “strong value proposition” based on superior efficacy and convenience, would be able to gain traction, she said.

Now, with data in both men and women, ViiV could go after Truvada in both populations, even though Gilead has historically indicated that women only make up about 10% of Truvada’s PrEP use. Cabotegravir’s “faster time to market and superiority improve the outlook for GSK’s franchise,” SVB Leerink analyst Geoffrey Porges wrote in a July note to clients.

Truvada was approved by the FDA in PrEP in 2012 for all uninfected at-risk individuals despite lacking data in women. That broad approval wasn’t given to Descovy, as the FDA only indicated it for men. Gilead’s now running clinical trials of both drugs, as well as an investigational agent called lenacapavir, in women at risk of HIV.

An injectable combo of cabotegravir and Johnson & Johnson’s rilpivirine, known as Cabenuva, has been approved as a once-monthly therapy to treat HIV in infected patients in Canada. GSK’s previous application was rejected by the FDA in late 2019 due to manufacturing concerns. A refiling has been accepted with an FDA target decision date set for Jan. 28, 2021. Bi-monthly Cabenuva data have also been positive.