Gilead currently controls the market for HIV prevention thanks to PrEP med Truvada. But GlaxoSmithKline, seeking an entry, now has proof its long-acting injectable cabotegravir works significantly better.
Injectable cabotegravir, given every two months, reduced HIV acquisition by 66% compared with daily oral Truvada after 1.4 years of median follow-up in the HPTN 083 trial, according to data presented at the virtual 23rd International AIDS Conference. That number is now confirmed as having crossed the statistical bar for GSK to tout superiority.
The win came over one year ahead of schedule, at the first interim analysis. “[B]oth the faster time to market and superiority improve the outlook for GSK’s franchise,” SVB Leerink analyst Geoffrey Porges said in a Wednesday note to clients. Consensus forecasts currently peg cabotegravir's peak sales at £750 million ($945 million), indicating it can grab about one-third of the current PrEP market, which is monopolized by Gilead.
The 4,570-subject study stopped early after an independent data monitoring panel found cabotegravir was highly effective. In the final analysis, just 13 HIV infections (0.41%) occurred in the cabotegravir arm, versus 39 cases (1.22%) among those who took Truvada.
Patients not sticking to their meds certainly contributed somewhat to the higher rate of infections seen in the Truvada arm, Porges noted. But it wasn't solely responsible for the win: ViiV labeled Truvada compliance as “high,” with 87% of a randomly selected subset of 372 Truvada recipients showing detectable tenofovir—one of two drugs that make up Truvada, a fixed-dose combo—in their blood. Seventy-five percent of those tested showed blood concentrations of the drug consistent with daily dosing.
Plus, Truvada compliance issues only underscore the importance of having long-acting options. A key advantage rests on the assumption that, by significantly cutting the frequency of dosing, at-risk patients will stay with their therapy regimens.
One of the challenges related to oral Truvada is that although individuals may start out adherent, that adherence wanes over time and, as a result, they become increasingly at risk of contracting HIV, Kimberly Smith, ViiV’s head of R&D, told reporters in a press briefing ahead of the data readout. “That’s something we can avoid by taking away that need for daily adherence,” she said, adding that there’s a lot of excitement for the long-acting injectable.
But again, adoption remains a question. Injectable cabotegravir will need to be administered by a healthcare professional. That could pose a hurdle at a time when COVID-19 is pushing physicians and patients to look at care options with little in-person interaction.
GSK plans to file bi-monthly cabotegravir for FDA approval in the first half of 2021, Porges noted. By the time it’s approved, the drug will need to compete against cheap, generic Truvada, which is expected to hit the market in September.
With an eye on that copycat entry, Gilead’s been busy switching PrEP patients to its newer Descovy, which boasts a better safety profile thanks to an improved tenofovir component. About 38% of individuals on PrEP are now taking Descovy, and Gilead’s aiming for around 40% to 45% by the end of 2020, Chief Commercial Officer Johanna Mercier said during the company’s first-quarter earnings call in April.
Descovy as a PrEP therapy is currently only approved in cisgender men and transgender women, the same population included in HPTN 083. A companion study, HPTN 084, is underway pitting cabotegravir against Truvada in cisgender women in Africa. Interim data from that trial could come out next year, maybe in time for a combined application together with HPTN 083.
Meanwhile, ViiV is pairing cabotegravir with Johnson & Johnson’s rilpivirine in a monthly HIV treatment called Cabenuva. Its application was previously slapped with an FDA complete response letter related to manufacturing issues. The company now plans to refile in the coming weeks.