Uncertain road ahead for lenacapavir, a new ‘breakthrough’ HIV prevention drug

All last year, the data on drugmaker Gilead Sciences’ injectable lenacapavir for HIV prevention (PrEP) were absolutely breathless. Studies of the PrEP drug for young women at risk for HIV in Africa, and then on different categories of cisgender and transgender people who have sex with men, found that with just two subcutaneous injections every six months, the drug’s preventive efficacy was essentially 100%. This topped the already extremely high preventive rates for existing daily oral versions of PrEP, mainly because participants didn’t have to remember to take it every day—post-injection, they were simply protected for a full six months at a time. (Lenacapavir has already been approved by the FDA as part of a treatment regimen for people with HIV who have already exhausted their other options, under the brand name Sunlenca.)

“The science around lenacapavir paints a very strong picture of its potential to revolutionize our approach to PrEP,” says Tim Horn, director of Medication Access at NASTAD, which helps state and local health departments administer and maximize federal HIV funding. 

He echoes what countless experts have said in the past year—that lenacapavir could finally be the factor that closes the gap in the U.S. between the vast majority of white men who have sex with men (MSM) who already take PrEP and have watched their new HIV rates plummet compared to Black and Hispanic/Latino MSM whose PrEP uptake is low and, relatedly, have watched their HIV rates stubbornly flatline or even rise in recent years. 

It’s widely believed that dramatically reducing the incidence of HIV among Black and Hispanic/Latino men who have sex with men is essential to ending HIV in the U.S.

The FDA is expected to approve lenacapavir for PrEP on June 19. In February, the FiercePharma industry blog reported: “With Gilead Sciences’ long-acting lenacapavir unlocking a reinvigorated focus on the pre-exposure prophylaxis (PrEP) market and growth in its three therapeutic areas driving momentum beyond HIV, the company appears to be firing on all cylinders as it approaches a crucial summer HIV launch.”

According to Carl Schmid, who heads the drug-access advocacy group HIV+Hepatitis Institute, Gilead is likely already working, pre-FDA approval, to get lenacapavir onto the formularies of private and public health plans, as well as negotiating rebates with them.

Says Jeremiah Johnson, executive director of the PrEP-expansion nonprofit PrEP4All: “Gilead’s efforts to diversify into cancer have yielded limited and mixed results, so they're still by and large an HIV company—and they’ve staked a lot on a successful launch of lenacapavir.”

As that launch approaches, myriad unknown factors could prevent lenacapavir from being the PrEP breakthrough it’s hoped to be in the U.S. (Whether Gilead has taken sufficient steps to make the drug affordable and available globally, especially now that the Trump 2.0 administration has drastically cut back on prevention support under the U.S. global AIDS program PEPFAR while also decimating USAID, is a separate story.) These include dynamics that predate as well as postdate the second Trump administration.

Let's take a look at some of the unknown factors that could converge to keep lenacapavir from becoming the HIV prevention game-changer in the U.S. it could be.

1. A pending case before the U.S. Supreme Court about whether most private U.S. plans can be required to fully cover HIV prevention medication

Advocates for a number of prevention measures across healthcare (such as PrEP or contraception) are anxiously awaiting the Supreme Court's decision (likely in June) on a case it heard arguments for in late April, Kennedy v. Braidwood Management. In the case, a Texas employer (Braidwood) refuses to follow a mandate of the U.S. Preventive Services Task Force (USPSTF), a congressionally authorized entity, saying that most private health plans in the U.S. must fully cover all forms of PrEP and related services, like labs—with zero cost-sharing on the patient's part. Braidwood refuses to have its health plans cover PrEP on religious grounds, claiming that PrEP promotes homosexuality. But it's possible that the Supreme Court may rule on whether USPSTF has the power to set 100% coverage mandates for several preventive health measures, from prenatal care to cancer screenings. 

Supreme Court justices posed questions during oral arguments suggesting they were sympathetic to keeping the mandates in place, but if they rule the other way, it could seriously hinder private plan coverage for lenacapavir, which Gilead will likely price expensively. In an email reply to POSITIVELY AWARE, the company would not share the potential price, but noted that it would not be based on what it charges for Sunlenca, the HIV treatment version of the same drug, which is about $42,240 a year. 

However, it is likely they will charge in the realm of what rival HIV drugmaker ViiV charges for Apretude (which is administered every two months), currently the only existing injectable for PrEP. That price is roughly $22,000. Meanwhile, the annual cost for Gilead's Descovy for daily oral PrEP is about $22,000, while the annual cost for daily oral generic versions of Truvada for the same purpose can be as low as $360. Health plans are highly incentivized to make patients opt for the generic version of PrEP, setting up barriers to choosing the more expensive versions. (Complaints that such plans have set a high barrier to covering Apretude are common.)

However, even if the court upholds the mandates, they have thus far proven hard to enforce. Pharmacists and patients often don't know about them, making it easy for plans to pretend they don't exist; even when patients do, pushing enforcement can entail appealing a denial to the health plan or even having to file a complaint with one's state insurance department. All these reasons are why patients might be more inclined to skip the hassle of getting lenacapavir and go on a daily oral generic instead.

Even if the mandates are upheld, Department of Health and Human Services secretary Robert F. Kennedy, Jr., who has not shown much support for domestic HIV prevention and has even expressed skepticism over the fact that HIV causes AIDS, would be able to restaff USPSTF in his favor or even rescind mandates. This is according to one industry expert who asked to remain anonymous because they did not have permission from their employer to speak for this story. This person also said that it was unclear whether the Supreme Court ruling would cover as-of-yet unavailable forms of PrEP (including lenacapavir).

2. Potential dramatic cuts to several programs that fund HIV treatment and prevention measures

As this is being published, a largely Trump-loyal, GOP-majority Congress is hashing out a budget that, per President Trump's wishes, could cut deeply into funding streams that have facilitated and covered PrEP access the past decade or so. Recently, the Trump administration released its vision of a FY2026 budget that preserves funding of the Ending the Epidemic initiative, which was begun in President Trump’s first term, but cuts all other preexisting CDC prevention and epdemic-tracking funding, which would make for a spotty and possibly inadequate funding picture in the years ahead.

The biggest block to lenacapavir coverage, however, would be significant cuts to Medicaid, the health coverage of about a fifth of Americans. Those cuts could very likely come in the form of stripping back so-called "expanded Medicaid," which significantly raised the income cap on coverage particularly in low-income red states—the very states where HIV rates are rising or remain flat among MSM of color.

In recent weeks, House of Representatives Speaker Mike Johnson has suggested that lawmakers would rule out some of the harshest cuts to Medicaid, largely at the behest of GOP reps from swing districts fearful of losing reelection should major cuts impact their constituents. Because of such reps—including New York's Mike Lawler, who recently penned an open letter urging the preservation of HIV funding—"we're starting to see some cracks in the Republican bloc" to hit Medicaid hard, says PrEP4All’s Johnson.

But Speaker Johnson is also facing pressure from hard-line reps who want to see major cuts. So the fate of the program—and its ability to cover lenacapavir for beneficiaries—is very much up in the air.

3. Possible reluctance of health plans to cover lenacapavir...

The modest success of Apretude, the existing injectable PrEP option, might serve as an indication of challenges ahead for lenacapavir: As of early 2024, only a tiny percentage of PrEP takers in the U.S. were on Apretude two years after its FDA approval; uptake was not even impressive in large cities like NYC and S.F., whose large middle-class gay male populations have led overall PrEP uptake in the past decade-plus. 

This could be partly because most health plans require doctors and patients to prove that patients have already "failed" the far cheaper generic oral daily PrEP option (say, because they could not stick to daily self-dosing). And again, even if the Supreme Court upholds USPSTF mandates, which apply to most private U.S. health plans, there is no guarantee that the plans will honor those mandates, or that patients and regulators can enforce them.

4. ...and of people to take lenacapavir

One possible reason for the low uptake of Apretude may also be that many takers report severe pain (that sometimes increases rather than decreases over days) in the buttocks after the every-other-month intramuscular injections. (Although data from Apretude’s clinical trial showed that the vast majority of injection site reactions (ISRs) were mild or moderate, Reddit threads of Apretude takers suggest that, at least for some, the pain was severe and sustained enough over days that they switched to oral daily PrEP.) The regimen also requires takers to show up at a health provider to receive the injections rather than merely pop their pills daily at home. Also, the product must be sent to a health provider rather than picked up at a pharmacy by the patient, which can complicate access and reimbursement.

These factors may be less of an issue for lenacapavir because the drug requires only two shots yearly rather than six. However, a majority of participants in lenacapavir trials reported injection-site pain, although it is difficult to say whether the pain was worse or lasted longer than the pain from Apretude.

Asked why it thought lenacapavir might do better than Apretude, a representative for Gilead replied in an email: "We have been actively learning from and listening to stakeholders to understand both what is, and what is not, working well today to ultimately support effective implementation."

All eyes on Gilead

With so many factors in the air and out of Gilead’s control, advocates say that the company needs to be doing all it can not only to lobby D.C. for the preservation of federal programs thats cover its drugs but to facilitate education and promotion of lenacapavir as well as build the infrastructure to deliver it. This is more important than ever, advocates say, as the federal government drops or dramatically cuts funding and programs—such as the CDC’s HIV prevention and EHE—for those very purposes.

Says Amy Kililea, an assistant professor at Georgetown University who follows access and coverage for HIV issues, “Gilead alone isn’t a stand-in for a functioning public health system,” but at the same time, “we need Gilead more than ever now.” With lenacapavir, she wonders, “Will they be launching a [charitable patient assistance] program different from the ones they already run? Obviously Viiv's access programs for Apretude haven't reached enough takers, so what lessons has Gilead learned from that?” 

For example, might Gilead consider launching a so-called “subscription model” in which it negotiates a flat price with interested states for a large supply of lenacapavir, after which the states promote the regimen and connect residents to it? The company did something like this with its breakthrough hepatitis C cure drugs in Louisiana and Washington. (Although it should be noted that that regimen is a roughly three-month one-time deal whereas someone can be on PrEP indefinitely. Also, at least one study found that the program yielded more new subscriptions in Louisiana than in Washington.)

Asked if Gilead would innovate new ways of getting lenacapavir out there, the rep replied via email: “There will be an Advancing Access program for lenacapavir for PrEP.... [that can] provide information to help patients access their prescribed Gilead medication.” But this largely sounds like the existing program that puts the onus on patients and doctors to initiate the charity process—not one that would take extraordinary measures, such as intensive work with state health departments and community-based organizations in high-need areas.

As for whether Gilead is lobbying in D.C. to preserve existing HIV funding, the rep replied: “We continue to engage with the Administration and Congress to encourage a balanced policy agenda that prioritizes innovation, HIV treatment and preventative care and most importantly, the needs of patients.”

A clearer read on lenacapavir’s future in the U.S. will emerge in the coming weeks, as Congress hammers out a budget between House and Senate versions and the Supreme Court releases its ruling on Braidwood. But as of now, there’s a very good chance that a drug that performed spectacularly in highly controlled trials could have little impact in a real-world setting fraught with so many barriers to promotion, distribution and coverage. 

Says Schmid: “Gilead is likely doing a lot on their own [to set up lenacapavir uptake], but we absolutely need the federal government as well.”

He is echoed by Horn: “We may be introducing a new PrEP tool in the middle of significant cuts in funds going to states, localities and community organizations. We all need to put our thinking caps and leave no stone unturned in terms of how we leverage this.”

Unless this happens, says the anonymous source, “We'll see lenacapavir used primarily by relatively affluent gay men in urban areas. I don’t know that it will fundamentally change the patterns of HIV transmission in this country.”

And that would be the story of PrEP so far in its decade-plus history in the U.S.: Dramatic reductions in new HIV acquisitions among middle-class and largely white men who have sex with men while failing to accomplish the same for Black and Hispanic men.