Long-Acting Cabotegravir Injection Performs Better as an HIV PrEP than Daily Pills

By Pavel Ryzhov, Ph.D.

Since the discovery of HIV in 1981, the search for a preventive agent has been a pursuit for generations of scientists. The strides made in our understanding of disease progression, the protective measures taken to curtail spread, and the concurrent development of novel treatments, have all significantly improved the mortality rate and quality of life in AIDS patients [1].

The daily pre-exposure prophylaxis (PrEP) regimen involving Gilead Sciences’ pill, Truvada, was FDA approved in 2012 to reduce the probability of HIV infection in high-risk patients. However, the stringency of this treatment makes adherence difficult and the need for a less labor-intensive therapy has become all the more pressing [2]. Now, the results from a Phase IIb/III clinical trial conducted by a global HIV focus company is about to challenge this standard of care [3].

ViiV Healthcare is a firm whose majority stake is owned by GSK with Pfizer and Shionogi Limited being shareholders. According to the recent press release from the company, its lead candidate drug, cabotegravir {CAB LA (long-acting)}, has demonstrated superior effectiveness in preventing HIV over Truvada, (emtricitabine/tenofovir disoproxil fumarate or FTC/TDF).

HPTN 083 study – Cabotegravir vs. Truvada

Cabotegravir is a small molecule integrase inhibitor, while FTC/TDF combo drug targets HIV’s nucleoside reverse transcriptase. Specifically, this head-to-head quadruple-blinded randomized study demonstrated that the long-acting cabotegravir was 69% (95% CI 41%-84%) more effective than FTC/TDF in preventing HIV acquisition.

Among the 4,600 individuals who participated in the study, 50 of them contracted HIV. From that, 12 participants were administered cabotegravir (CAB LA) intramuscular injections every two months, and 38 were subjected to daily oral FTC/TDF treatments. The HIV acquisition rate of cabotegravir and FTC/TDF was 0.38% and 1.21%, respectively.

With this result, the trial achieved its primary endpoint of non-inferiority and offered compelling evidence that the infrequent administration of CAB LA was effective as compared to the daily dose of the competitor. As a result, the independent review board and NIAID have recommended an early halt to the study. They have further recommended releasing the results, and administer CAB LA to the rest of the FTC/TDF arm patients.

Notably, this study enrolled HIV-negative men who have sex with men (MSM) and transgender women who have sex with men (who are considered HIV infection risk). Two-thirds of the participants were under 30 years, and 12% were transgender women. Half of the participants in the US identified as African-American or black. Another ongoing study, also co-sponsored by NIAID and ViiV Healthcare, aims to elucidate the effectiveness of CAB LA among women. The trial has already crossed 3,000 enrolled women across 7 countries in Africa.

Cabotegravir / Rilpivirine Combo

With the results of this clinical trial announced, it is worth revising a previous new drug application (NDA) from ViiV Healthcare filed based on the positive results from ATLAS and FLAIR clinical trials. The two trials compared the long-acting cabotegravir in combination with rilpivirine (non-nucleoside reverse transcriptase inhibitor) against the standard of care in HIV-1 infected individuals to assess non-inferiority.

The NDA was subsequently rejected by the FDA and the drug combo was not approved on the basis of Chemistry Manufacturing and Controls. ViiV has started working with the agency towards the next steps in the resubmission process. It would be very interesting to see how these new trial results would affect the previous NDA and the subsequent journey of CAB LA treatment.

Regardless, the positive outcome of this study shows the progress that we have made to address the pressing issue of HIV infection rate and it is a matter of time before these medicines will become available to people who need it.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: Kainos Medicine’s New HIV Drug Kicks Off Phase III Trial in China

References

1. https://www.nejm.org/doi/10.1056/NEJM199803263381301
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224042/
3. https://viivhealthcare.com/en-gb/media/press-releases/2020/may/global-hiv-prevention-study-to-stop-early-after-viiv-healthcares/

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Author

Pavel Ryzhov