Some two million people may get access to lenacapavir, the twice-yearly antiretroviral injection that prevents HIV injection, within the next three years, thanks to the Global Fund and United States President’s Emergency Plan for AIDS Relief (PEPFAR).

The initiative is contingent upon regulatory approval from the US Food and Drug Administration (FDA), national pharmaceutical regulators, and a recommendation from the World Health Organization (WHO).

It is being supported by the Children’s Investment Fund Foundation (CIFF) and the Bill & Melinda Gates Foundation (BMGF) 

At present, lenacapavir is licensed in the US and other countries as a treatment for adults with drug-resistant HIV. 

However, in two clinical trials it has shown to almost completely block HIV when used as pre-exposure prophylaxis (PrEP).

Not a single one of the 2,138 women in PURPOSE 1 trial who received lenacapavir contracted HIV. In the PURPOSE 2 trial involving men and gender-diverse people, only two of the 2,179 participants became infected during the trial – a success rate of over 99%.

In both trials, lenacapavir was tested alongside oral PrEP and found to be superior as the twice-a-year injection is much easier to adher to than taking daily pills.

“We cannot reach a sustainable HIV response without rapidly reducing the 1.3 million new HIV infections that occur worldwide every year,” said Ambassador Dr John Nkengasong, US Global AIDS Coordinator head of PEPFAR in a statement on Tuesday.

“Lenacapavir offers a potentially tremendous opportunity to transform the impact of HIV programs to ensure adolescent girls and young women, key populations, and others who could benefit have access to highly effective HIV prevention, testing and treatment services and to end HIV/AIDS as a public health threat by 2030.”

In October the medicine’s manufacturer, Gilead, announced that it had signed non-exclusive, voluntary licensing agreements with six pharmaceutical companies to manufacture and supply generic versions of lenacapavir for 120 primarily low- and lower-middle-income countries.

Global regulatory filings

“Data from both PURPOSE 1 and PURPOSE 2 will support a series of global regulatory filings for lenacapavir for PrEP that will begin by the end of 2024,” Gilead announced.

The FDA has granted lenacapavir for PrEP “breakthrough therapy designation”, which is intended to expedite the development and review of new drugs that may demonstrate substantial improvement over available therapy.

The FDA has also granted a “rolling review” for lenacapavir for PrEP, which allows the FDA to fast-track the review of a drug application by allowing a company to submit sections of the application for review as they are completed.

In September, WHO announced that it is “working rapidly to convene a guideline development group with experts, ministries, partners and communities”.

This group will develop and issue guidelines based on a “rigorous assessment of the potential of lenacapavir for HIV prevention, evaluating key aspects such as efficacy, safety, cost-effectiveness, values and preferences from stakeholders and communities, and global scalability, among others”.

A WHO spokesperson told Health Policy Watch on Tuesday that the Guideline Group meeting will be held from 28-30 January and would have a recommendation by July 2025, at the latest.

“WHO has already listed lenacapavir on the Expression of Interest list (EOI) and has provided guidance on bioequivalence,” the spokesperson added.

It is also working to ensure rapid regulatory approval via the FDA and European Medicines Agency EMA Medicines4All pathways.

Once a Stringent Regulatory Authority (SRA) approval is obtained, the manufacturer can apply for pre-qualification using the abridged pathway.

“WHO is working with potential early adopter countries to anticipate and prepare for guidelines and country regulatory approvals,” the spokersperon said.

Excited by the promise

“At the Global Fund, we are incredibly excited by the promise of lenacapavir and its potential to help us achieve a further significant reduction in new infections among individuals at high risk of acquiring HIV,” said Peter Sands, Executive Director of the Global Fund. 

“As part of this coordinated effort, the Global Fund, PEPFAR, CIFF, and BMGF will work with Gilead and the voluntary licensing manufacturers to accelerate affordable and equitable access, so that more people can benefit from this powerful innovation from day one.”

CIFF founder and chair Sir Chris Hohn, said that innovations like lenacapavir can profoundly impact the lives of millions.

“It will be a travesty if the communities who need it most don’t have access. That is why this collaboration is so essential to ensure that lenacapavir is available as soon as possible for those who need it the most,” said Hohn.

Image Credits: Gilead.