An active pipeline
There are 24 new PrEP products in development, as well as 24 other multipurpose prevention technologies (MPTs), which are combination products containing PrEP and one or two other medications.
These 48 products include 28 unique antiviral and contraceptive drugs and 12 delivery methods or formulations. “Why so many?” Dr. Hendrix asked. “Many will not make it through development.”
Pills that include HIV PrEP and contraception or PrEP and sexually transmitted infection (STI) treatment are being evaluated, for example. “HIV risk, pregnancy risk, and other viral STIs overlap. Ideally, you can have one target for all three. That would increase efficiency of dosing and adherence,” Dr. Hendrix said.
Dual prevention pills (DPPs) hypothetically provide HIV PrEP and contraception better than either product alone, Dr. Hendrix said. Plans are to market them as family planning or women’s health products to avoid any stigma or distrust associated with HIV PrEP. An initial rollout is planned in 2024 in sub-Saharan Africa where the unmet need is highest, he added.
“Imagine how effective this could be in women in the United States,” Dr. Hendrix said. “My hope is fourth-quarter 2024” availability in the United States.
A way to prevent STIs and HIV in an all-in-one product “would be terrific,” Dr. Hendrix said.
“I think we’re going to see a lot more innovation going in that direction. The pill is close. The other things are going to be further off because the regulatory pathway is a little more complicated.”
Longer lasting protection?
All of the innovations have gone one of two directions, Dr. Hendrix said. One direction is to make PrEP even longer acting, “so that you have even less to worry [about] in terms of adherence.”
Going forward, “most of the focus has all been on continuously acting or long-active PrEP. It’s getting longer and longer: We’ve got 2 months, and they’re looking at a 6-month subcutaneous injection,” Dr. Hendrix said. The investigational agent lenacapavir is in development as PrEP, as well as for HIV treatment.
“This could get us from 2 to 6 months,” Dr. Hendrix said.
Some of the subcutaneous implants look as if they could provide PrEP for up to 12 months, he added. “An implant could also avoid peaks and troughs with bi-monthly injections.”
On-demand PrEP
The other direction is on-demand. “This is for the folks that don’t want drug in their body all the time. They only want it when they need it. And a twist on that ... is actually using products that are already used with sex now but medicating them.”
On-demand rectal options include a medicated douche and a fast-dissolving insert or suppository.
Fast-dissolving vaginal inserts are also in development. “These inserts are small, easy to store, inexpensive, and possibly inapparent to a partner,” Dr. Hendrix said.
Phase 2 studies will need to determine if these products “fit into folks’ active sex lives,” he said. “There’s still a need for human-friendly, human-designed products.”
A rectal microbicide that got as far as Phase 2 research provides a cautionary tale. The concentrations and the biology worked fine, Dr. Hendrix said. “It was a gel with an applicator, and it just was not liked by the folks in the study.” He added, “Your adherence is going to be in the tank if you’ve got a product that people don’t like to use.”