Pipeline for new PrEP drugs has ‘exciting’ options

SAN FRANCISCO, 17 October 2022—Product launches for novel HIV pre-exposure prophylaxis (PrEP) drug formulations are looking promising, a speaker said at the 2022 ACCP Global Conference on Clinical Pharmacy.

“There are a lot of options coming down the pipeline for PrEP, so this really excites me,” said Emily Drwiega, PharmD, BCIDP, BCPS, AAHIVP, an infectious diseases/HIV clinical pharmacist at the University of Illinois Health, in Chicago.

One novel formulation already on the market is cabotegravir (Apretude, ViiV Healthcare), an extended-release injectable suspension that was approved by the FDA in December 2021. The drug is indicated for use in at-risk adults and adolescents with body weight of 77 pounds or more. The medication, an integrase strand transfer inhibitor, is given first as two initiation injections administered one month apart, and then every two months thereafter.

On the investigational front, there is another formulation of cabotegravir—a long-acting subcutaneous implant—that offers some unique dosing options. The medication is in preclinical trials, with evaluations of pharmacokinetics and safety in non-human primates in a variety of doses and durations, noted Dr. Drwiega, who is also a visiting clinical assistant professor of pharmacy practice at the University of Illinois Chicago’s College of Pharmacy.

One study (J Control Release 2021;330:658-666) suggested the drug could be detected in the experimental animals for up to a year, she said, and the majority of subjects had an undetectable cabotegravir concentration within two weeks of implant removal. This is a feature that could be desirable for patients if they have adverse effects or become pregnant and want a much more rapid decline in concentration than an intramuscular injection, she said.

Other implants also are being studied for tenofovir alafenamide, as well as the combination product tenofovir alafenamide plus emtricitabine. (Gilead’s Biktarvy, a combination of bictegravir, emtricitabine and tenofovir alafenamide, is currently available as a tablet.)

Another PrEP long-acting pipeline agent, an injectable formulation of lenacapavir, has advanced to clinical trials, Dr. Drwiega said. The PURPOSE 1 trial (ClinicalTrials.gov Identifier: NCT04994509), for example, is assessing the drug for PrEP in adolescent girls and young women at risk for HIV infection, Dr. Drwiega noted.

From a regulatory standpoint, lenacapavir, a capsid inhibitor, is farther along for multidrug-resistant HIV. The twice-yearly subcutaneous injection was approved by the European Commission in August for that indication, but not yet for PrEP. The drug is on a similar regulatory path in the United States.

The initial distribution of lenacapavir is a little slow, so that “may require some type of oral overlap or lead-in during the initial injection, until concentrations are sufficient for HIV prevention,” Dr. Drwiega said.

Early in vitro studies of lenacapavir demonstrated an absence of cross-resistance to other currently used antiretroviral therapies, so this may be beneficial in that clinicians will still have all initial treatment options as therapy for incident infections if they occur, she said.

Other products under study are vaginal rings—flexible, silicone rings that slowly release drugs. A potential benefit is that they can deliver higher concentrations of drug locally while reducing systemic exposure, Dr. Drwiega noted. There also is the potential for self-insertion, which could be helpful for patients who won’t need to visit a provider for the insertion.

Dapivirine, another promising PrEP pipeline agent, is a non-nucleoside reverse transcriptase inhibitor being studied as one-month and three-month formulations. The phase 3 ASPIRE and Ring trials of the one-month formulation have been completed, along with follow-up HOPE and DREAM studies, with “promising results,” Dr. Drwiega said.

Once-monthly dapivirine rings have been approved for use in some sub-Saharan African countries. However, the product was voluntarily withdrawn from FDA consideration after the developer, the nonprofit International Partnership for Microbicides, received feedback from the agency that the data are unlikely to support approval in the United States at this time. The three-month formulation is in phase 1 studies.

“We’ll be seeing those pharmacokinetic studies coming soon, hopefully, so I don’t think that this is going away despite the withdrawal from the approval process,” Dr. Drwiega said.

Additional vaginal rings are in development for the release of tenofovir disoproxil fumarate and for vicriviroc, as well as many others in early preclinical and phase 1 clinical trials underway in combination with antiretroviral therapy as well as contraception.

A variety of topical products are in development for PrEP, she said, including vaginal/rectal gels, dissolving vaginal films, sustained-release vaginal tablets, suppositories and enemas.

By Karen Blum