GSK sub’s injectable outperforms Gilead in late-stage PrEP trial

Since 2012, when Truvada was first approved as a preventative treatment for HIV, Gilead has had a monopoly on PrEP, or pre-exposure prophylaxis. Now, in a large NIH-backed trial, a new drug from a pair of Big Pharma rivals looked just as effective, if not more.

Investigators tested a long acting injectable from ViiV Healthcare — the joint HIV initiative between Pfizer and GlaxoSmithKline — against Truvada across 4,600 people at risk for HIV infection. The trial, although only powered for non-inferiority, showed those on the long-acting injectable were 69% less likely to contract HIV than those on Truvada, a once-daily pill.

The drug, called cabotegravir, enters into a shifting landscape for PrEP. Truvada is set to come off patent protection next year, setting the stage for the first generic competition. Gilead hopes their new formulation for treatment and prevention, Descovy, will prove a similar blockbuster, notably offering a better safety profile, but they are also facing lawsuits from activists accusing them of manipulating development times to extend their monopoly and from the US government, who in a rare move has accused the drugmaker of failing to license their intellectual property on the use of Truvada as HIV prevention.

ViiV and the NIH had until recently been running the trial as a superiority trial, study protocol chair Raphael Landovitz told Science. But earlier this year Covid-19 began disrupting the study, closing 11 of 43 trial sites and preventing participants at other sites from coming in. In April, investigators asked the data and safety monitoring board to change the study’s endpoints to non-inferiority, to ensure the study could be completed with an uncompromised data set.

On May 14, the DSMB did a scheduled review and found it had already met that threshold. The data showed 12 infections occurred in the cabotegravir group versus 38 in the Truvada group, or a 0.38% chance of infection versus 1.21%.

”We are thrilled with the results not only because of the high efficacy of cabotegravir but also because we have demonstrated high efficacy in a study that adequately represents some of the populations most disproportionately impacted by HIV — black MSM in the US, young MSM globally and transgender women,” ViiV R&D chief Kimberly Smith said in a statement, using an academic shorthand for men who have sex with men.

Truvada is highly effective at preventing HIV, and other studies have shown those who are infected while on the regimen missed had missed doses of the once daily pill. One of the goals of cabotegravir was to improve compliance, as it only has to be given once every two months.

Investigators are still unsure, though, why there were 12 infections in the cabotegravir arm, telling Science it could be because of weight differences or because infection occurred early in the trial, when patients in both arms had been required to take Truvada.

The company could face an uphill battle for approval, though. In December, the FDA hit ViiV with a CRL on its application to get a combination of cabotegravir and the antiviral rilpivirine approved as a monthly injectable treatment for HIV. ViiV said the issue was around chemistry manufacturing and controls — concerns that say little about the drug’s effectiveness but have held up companies for long periods in the past.

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