Second Pivotal Trial of Twice-Yearly HIV Prevention Injection Safe and Highly Effective

AVAC welcomes the groundbreaking results of the PURPOSE 2 HIV prevention study of twice-yearly injectable lenacapavir for PrEP among 3,200 cisgender men, transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Among more than 2,000 people in the trial who received lenacapavir, there were only two HIV infections.

Press Release

Second Pivotal Trial of Twice-Yearly HIV Prevention Injection Safe and Highly Effective: PURPOSE 2 Trial Among Gay Men, Trans and Nonbinary People  

AVAC Calls for Accelerated Regulatory Review and Ambitious, Equitable Access Plans

New York City, September 12, 2024 – AVAC welcomes the groundbreaking results of the PURPOSE 2 HIV prevention study of twice-yearly injectable lenacapavir for PrEP among 3,200 cisgender men, transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Among more than 2,000 people in the trial who received lenacapavir, there were only two HIV infections.

Preliminary safety and efficacy results were reported today by Gilead Sciences, the drug’s developer. An independent data and safety monitoring board (DSMB), at a scheduled review of the trial data, found the regimen to be safe and highly effective, with a 96% lower HIV rate compared with the expected background incidence of HIV infection and 89% lower compared with oral TDF/FTC. These results follow the results of PURPOSE 1, released earlier this year, that showed 100% efficacy of lenavcapavir among cisgender women in South Africa and Uganda.

“This is the second impressive result for this new HIV prevention option, opening up more possibilities for choice for even more people to find an option that is right for them,” said Mitchell Warren, AVAC’s executive director. “Beyond expanded choice, a twice-yearly injection has the potential to transform the way we deliver HIV prevention to people who need and want it most – from an easier to follow regimen for individuals to a decreased burden on healthcare systems that are stretched to the limit. But these data only matter if the field moves with speed, scale and equity.”

“Having results from a trial population that includes trans men and women, nonbinary people and gay men is an important milestone for community inclusion in HIV prevention studies,” said Kenyon Farrow, AVAC communications director and PrEP user since 2015. “I am excited that people who want to use PrEP or who fear stigma or discrimination, may soon have the possibility of another option that could be much easier to use and provide more discretion. It is imperative that we accelerate planning for rollout of lenacapavir. We know that even with the most ambitious timeline, it will take time for lenacapavir to be rolled out to all who need and want to use it.”

The study evaluated the safety and efficacy of twice-yearly injectable lenacapavir for PrEP compared to once-daily oral emtricitabine/tenofovir and background HIV incidence. All trial participants will now be offered lenacapavir. Additional studies in critical populations, including PURPOSE 3 among cisgender women in the US and PURPOSE 4 among people who inject drugs, are also underway. It will be imperative to understand how today’s results influence these trials. A schematic of the suite of studies is here.

“We applaud Gilead’s commitment to Good Participatory Practice in this and the other PURPOSE studies, especially through the inclusion of multiple populations in the PURPOSE studies and a commitment to including community voices in trial design and in access plans” said Stacey Hannah, AVAC director of research engagement. “Access and implementation plans must be shaped and informed by continuous, robust participatory engagement. AVAC and our partners look forward to continuing engagement with Gilead and other key stakeholders in this process.”

Importance of Access and Equity 

Gilead said it is committed to making lenacapavir available for prevention in countries where it is needed most and to granting direct voluntary licenses for longer-term availability. Today’s results make it clear that Gilead, along with regulatory and normative agencies, funders and civil society, must work on an accelerated timeline to ensure broad and timely access to individuals and communities everywhere.

“In an updated access statement today, Gilead committed to beginning global regulatory filings by the end of 2024 and to facilitating faster access to target populations and countries,” Warren said. “This raises the stakes to accelerate speed, scale and equitable access. Gilead needs to urgently grant these licenses even before regulatory approval and name its prices, so that funders can prepare to accelerate product introduction. And WHO must urgently initiate its guideline review process so that lenacapavir, if approved by regulatory agencies, can be immediately added into the PrEP method mix. There is no time to waste if we are to translate these exciting clinical trial results into actual public health impact.”

“We now know that lenacapivir for PrEP is safe and highly effective among a range of populations,” Farrow added. “Even as we await regulatory submission and review, there is urgent work to be done now by communities, policy makers, funders and program implementers to design and build HIV prevention programs and prepare health systems to deliver the growing array of biomedical PrEP options, including the addition of twice-yearly injectable lenacapavir. The full range of PrEP products—including oral PrEP—must be made feasible choices for all people who need and want HIV prevention options.”

Lessons learned from rollout of daily oral PrEP, and more recently the dapivirine vaginal ring and injectable cabotegravir, can help speed regulatory approval and guideline development in key countries, design of effective programs, and community understanding of and acceptance of lenacapavir for PrEP. 

“For many years, AVAC and a coalition of international partners have been planning for successful, accelerated introduction of PrEP at scale and with equity. There can be no excuses, no delays, and no repeats of the failures of oral PrEP rollout. We must move with speed, scale, and equity to ensure lenacapavir has the impact we need to prevent new HIV infections,” said Warren.

###

About AVAC

AVAC is an international non-profit organization that provides an independent voice and leverages global partnerships to accelerate ethical development and equitable delivery of effective HIV prevention options, as part of a comprehensive and integrated pathway to global health equity. Follow AVAC on Twitter @HIVpxresearch; find more at www.avac.org and www.prepwatch.org. 

Avac Event

Do Vaginas Demand Perfection? Implications for Event-Driven PrEP

Dr. Jenell Stewart (University of Minnesota, Hennepin Healthcare) joined The Choice Agenda to discuss and analyze recent research on HIV PrEP and implications for event driven PrEP across sex and gender.

Recording / Slides

HIV leaders say it’s time to end the long wait for long acting products

Dear Advocate, 

How do we translate recent scientific advances in long-acting HIV prevention and therapy into public health impact? Read answers in this new The Lancet HIV commentary from a distinguished group of authors including our Executive Director, Mitchell Warren, AVAC board members, Linda-Gail Bekker, Solange Baptiste Simon, with partners Francois Venter, Kenly Sikwese, and others: The long wait for long-acting HIV prevention and treatment formulations. 

Major advances in long-acting HIV treatment and prevention, including the latest PURPOSE 1 results of lenacapavir for PrEP, hold great promise for achieving global targets. However, planning to coordinate among stakeholders, including pharmaceutical companies, governments, and multilateral organizations to deploy and ensure equitable access to these products, particularly in low- and middle-income countries, requires immediate action.  

“Civil society organisations and HIV activists have been instrumental in holding pharmaceutical companies, financial donors, governments, and international organisations accountable for commitments to the international HIV treatment response for decades,” the authors write. “These organisations and activists are needed to promote transparency in pricing, challenge restrictive patent practices, advocate for affordable and widespread availability of drug innovations, prevent companies from restricting broad access to medications, and require funding to allow this work to be done independently.” 

Key Messages

  • Long-acting antiretrovirals are perhaps the greatest advance in HIV care in over a decade and provide great promise towards achieving global HIV prevention and control programme targets. 
  • Current long-acting agents are firmly under the control of originator pharmaceutical companies and remain unavailable or cost-prohibitive across much of the globe. 
  • If action from the broader HIV community is stagnant, the populations who are most in need of these long-acting agents are unlikely to receive any benefit until well into the 2030s, resulting in a large number of preventable HIV infections. 
  • Coordination by international agencies, with assistance from relevant financial donors and stakeholders, will be needed in the complex research and access programmes required to provide widescale use of these indispensable products to people living with HIV or affected by HIV. 

Resources on Long-Acting HIV Prevention

The Lens on LEN: this primer for advocates shares the basics on injectable lenacapavir as PrEP.

Long-Acting PrEP Status Update: this webpage shares graphics and information synthesizing the current status of long-acting PrEP products. It’s updated quarterly.

PrEP Products Overview: this page on PrEPWatch shares the status of PrEP products in development and approved.
Injectable Cabotegravir Evidence Gap Tracker: this webpage summarizes the latest insights from the Biomedical Prevention Implementation Collaborative (BioPIC) on injectable CAB for PrEP, links to learn more, and information on where evidence is still needed, mapped against priority evidence gaps.

Years Ahead in HIV Prevention Research: Time to Market: this downloadable graphic shows the potential time points when the next-generation of HIV prevention options might find their way into new programs.

What Happens to PrEP Initiations in Countries with Anti-Discrimination Policies?

Among 134 countries reviewed, 42 have comprehensive anti-discrimination policies covering a broad range of populations, while 24 lack any such policies. The remaining countries have adopted partial measures. Nations with comprehensive anti-discrimination policies, document significantly higher rates of PrEP initiation compared to those without such protections. Key studies show a strong link between supportive policies (which can enable PrEP eligibility, HIV self-testing, and lower age of consent for treatment, for example) and higher PrEP initiations.

Generic Cabotegravir Timelines

As CAB for PrEP is a long-acting, extended-release injection, bioequivalence (BE) testing takes time to determine whether the generic drug functions in the body similarly to the original drug. As shown in this timeline graphic, the BE study (as determined by WHO guidance) is the longest part of the development process for generic CAB. But other steps, such as selecting and licensing generic manufacturers and technology transfer could be done faster.

PxWire Volume 14, Issue No. 3

PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research and development, implementation and advocacy. Each issue includes updates, emerging issues and upcoming events. A PDF version of this report is also available.

Progress in PrEP Uptake

Oral PrEP initiations in Uganda were among the highest in the region, with sizable increases each quarter, until the enactment of the Anti-Homosexuality Act (AHA) in March 2023. Since then, the number of new PrEP initiations plummeted, and have since struggled to sustain rates seen in 2023. Public policies clearly matter.

Among 134 countries reviewed, 42 have comprehensive anti-discrimination policies covering a broad range of populations, while 24 lack any such policies. The remaining countries have adopted partial measures. Nations with comprehensive anti-discrimination policies, document significantly higher rates of PrEP initiation compared to those without such protections. Key studies show a strong link between supportive policies (which can enable PrEP eligibility, HIV self-testing, and lower age of consent for treatment, for example) and higher PrEP initiations.

An analysis presented at AIDS 2024, HIV Pre-Exposure Prophylaxis Policies Worldwide, by the Georgetown University Center for Global Health Policy & Politics and AVAC found that 69% of the 194 countries reviewed have approved at least one PrEP product. However, only 52% of these countries adhere to WHO guidance on PrEP eligibility, with regulatory approvals and national policies that support PrEP use for all populations or people at risk. This data reinforces the critical need for policies that support PrEP uptake.

PrEParing for New Products

Advocacy to accelerate licensing for new products can speed the process of generics manufacturing.

Three generic manufacturers—Aurobindo, Cipla, and Viatris—have licenses via the Medicinces Patent Pool to develop generic versions of injectable cabotegravir (CAB) for PrEP. These generic products are currently in development and expected to be submitted to regulatory authorities in the second half of 2026, with possible approval in 2027.

Does the Timeline Have to be this Long?

As CAB for PrEP is a long-acting, extended-release injection, bioequivalence (BE) testing takes time to determine whether the generic drug functions in the body similarly to the original drug. As shown on the timeline graphic below, the BE study (as determined by WHO guidance) is the longest part of the development process for generic CAB. But other steps, such as selecting and licensing generic manufacturers and technology transfer could be done faster. It is critical that generic manufacturers for new PrEP products, such as lenacapavir, star as soon as possible. This requires Gilead to pursue licensing even before regulatory submission, and to accelerate technology transfer and API development.

Product Updates

  • Data from HPTN 084 show that CAB for PrEP was generally well tolerated and safe for both pregnant cisgender women and their babies.
  • China has approved CAB for PrEP.
  • With PEPFAR support, Eswatini, Nigeria, and Ukraine are poised to introduce CAB for PrEP into their national PrEP programmes this quarter, and the South African government announced CAB supplies from PEPFAR will be launched in Q1/Q2 2025.

See AVAC’s Planning Matrix for more!

The Latest R&D in the Prevention Pipeline

Results from the PURPOSE 1 trial of injectable lenacapavir showing 100% efficacy in preventing HIV among cisgender women and adolescent girls dominated headlines at the AIDS 2024 conference. This Phase 3 trial, conducted by Gilead Sciences, involved over 5,000 participants from South Africa and Uganda and demonstrated superior results compared to daily oral PrEP options. See the New England Journal of Medicine publication, accompanying Editorial and our advocates’ primer to learn more about the results and what needs to happen next: Lens on LEN: The basics on injectable lenacapavir as PrEP.

Gilead’s PURPOSE 2 Phase 3 trial is ongoing and testing injectable lenacapavir as PrEP in the US, South Africa, Peru, Brazil, Mexico, Argentina, and Thailand, among cisgender men who have sex with men, transgender women, transgender men, and gender non-binary individuals. With 3,000 participants enrolled, initial results are anticipated in late 2024 or early 2025. Two other trials (PURPOSE 3 & 4) are currently recruiting in the United States, enrolling cisgender women and people who inject drugs, respectively. Enrollment for PURPOSE 5 in France and the UK is expected to commence in the latter half of this year. For more information about the lenacapavir trials, visit: An Overview of Lenacapavir for PrEP Trials.

Meanwhile, the bioequivalence study for the Dual Prevention Pill (DPP), designed to prevent both HIV and pregnancy, has concluded successfully, with each of the drugs functioning together in the body in a similar way to how they function alone. The promising results pave the way for regulatory submission and potential large-scale adoption, offering another significant tool in the fight against HIV and unintended pregnancies. Learn more about the DPP and find resources for your advocacy.

Prevention Playlist

AVAC develops a wide range of resources to inform decision making and action. Check out the latest:

Join

Read

Watch and Listen

Use

Press Release

Heeding Community Advocates’ Calls, CDC Funds PrEP Pilot Program, Allows Funds to Pay for Generic Medications

For media inquiries contact Michael Chancley at [email protected] 

Tuesday, August 6th, 2024 – For the first time ever, the U.S. Centers for Disease Control and Prevention will allow for funding to pay for generic PrEP medications as part of a new supplemental funding opportunity aimed at quickly scaling up equitable PrEP access in four jurisdictions. Advocates have been calling for such an initiative to serve as a pilot for a National PrEP Program for un- and underinsured individuals; a key component of which would involve the implementation of a user-friendly PrEP Pass that could eliminate cost and complexity as a barrier to medications, HIV testing, necessary lab work, and provider visits. 

Along with a previous decision by CDC allowing for grant funds to go toward ancillary PrEP services, this initiative marks the first time that jurisdictions will be able to purchase affordable, high quality generic medications– priced at less than $20 per month– to create a common sense public health approach to PrEP scale up that avoids navigating complex, fragmented coverage options. 

The initiative will also fund coordinators within health departments to advance the project in partnership with community partners and empower them to conduct a comprehensive review of insurance barriers to PrEP coverage.   

Leading advocacy organizations for a National PrEP Program, including PrEP4All, AVAC, HIVMA, and the PrEP in Black America coalition, enthusiastically support the initiative and urge eligible health departments to apply before the August 31st deadline. 

“This is a real opportunity to make an impact in our national efforts to scale up PrEP and end HIV as an epidemic. The entire advocacy community, after years of building an evidence base for this sort of approach to equitable uptake, is ready to take the successes and lessons learned from this initiative to Congress to advocate for a national program.” explains John Meade, Senior Program Manager for Policy at AVAC and co-founding member of PrEP In Black America.

Although both the application and project implementation timelines are short, advocates are hopeful that health departments will apply to be part of this historic initiative. 

“We think it’s important for any department thinking of applying to note that the notification of funding opportunity (NOFO) specifically includes selection criteria prioritizing jurisdictions in the Deep South and states that have not expanded Medicaid- meaning that it’s well worth it for those priority jurisdictions to get an application in. Also, there is flexibility on the timeline for grant implementation through 2026, so the short window shouldn’t discourage anyone.” says Michael Chancley, Communications and Mobilization Manager for PrEP4All and co-founding member of PrEP In Black America. 

“Our organizations want to sincerely thank the CDC for listening to our advocacy for this pilot and for also affirming that expanding PrEP infrastructure can help scale up novel sexual health interventions like doxy PEP. In particular, we really appreciate the efforts of Dr. Robyn Neblett Fanfair, who as the Director of the Division of HIV Prevention has undoubtedly worked hard to get this NOFO released after Congressional delays in passing the FY24 complicated matters further,” added Colleen Kelley, MD, MPH, FIDSA, HIVMA Chair-Elect.

In addition to the PrEP Pass, advocates have called for the initiative to expand prescriber access points throughout communities, including through leveraging innovative use of telehealth, and to develop campaigns made by and for PrEP users and potential PrEP users from underserved communities. 

“This initiative aligns squarely with what the PrEP advocacy community has identified as what’s needed. Our organizations are ready to work with health departments to help provide context on how this grant opportunity came to be and why it is so important in advancing our movement for a National PrEP Program. We look forward to doing everything we can to support the innovative public health leaders who are ready to take full advantage of this opportunity.” says Jeremiah Johnson, MPH, PrEP4All Executive Director.

Read the full press release in PDF format here.

Avac Event

PrEP Your Booty – The Launch of HPTN 106 “Rev Up”

HPTN 106 (REV UP) is an innovative clinical trial from the HIV Prevention Trials Network that will investigate the safety and acceptability of a tenofovir-based rectal douche for HIV prevention among cisgender men and transgender women who have sex with men. This webinar featured researchers leading the study.

Speakers:
Dr. Craig Hendrix, Johns Hopkins University School of Medicine
Dr. Mark Marzinke, Johns Hopkins University School of Medicine

Moderator:
Jim Pickett, The Choice Agenda

Co-sponsor:
HIV Prevention Trials Network

Recording  / Webinar Slides / Resources

Avac Event

Let’s Talk LEN: What global advances in HIV prevention mean for Black communities in the US

Groundbreaking results from the PURPOSE 1 trial conducted among cisgender Ugandan and South African women have changed the injectable PrEP global landscape. This webinar explored the implications of these findings for US Black populations.

This webinar was co-hosted by PrEP in Black America, Black Public Health, Federal AIDS Policy Partnership (FAPP), AVAC, and APHA.

Recording / Bekker Resource / Campbell Resource