Sunlenca looks great for highly drug-resistant HIV. Will it serve a broader purpose?

Right before Christmas, the Food and Drug Administration (FDA) approved the injectable drug Sunlenca (lenacapavir) for use in adults with heavily drug-resistant HIV—those folks (often HIV longtimers) whose HIV has developed mutations against many or all preexisting antiretroviral therapy options, making it very hard for them to get to undetectable status or to have a health-boosting increase in CD4 cells.

The approval was based on the year-long, multicenter CAPELLA study, which included 72 patients with heavy drug resistance and high viral loads despite being on the best possible regimen. In the study, 81% of patients who added Sunlenca to their existing best regimen attained undetectable status after 26 weeks, compared to a dramatically smaller percent in the group that added a placebo (sugar pill) to their existing best regimen.

At the one-year mark of the study, those numbers held. Also, the percent of people in the Sunlenca group with CD4 counts of 200 cells/mm³―the minimum for an immune system to avoid advanced HIV disease―or higher increased from 25% pre-treatment to 60% after. The study also found that the drug was safe, well tolerated, and showed little significant difference in efficacy (given how small the study was) across age, race, or gender.

The approval may well be a blessing for the estimated 12,000 Americans with heavily drug-resistant HIV—a number that once was much larger before a powerful new wave of HIV drugs came online in the 2000s and 2010s.

In an interview with TheBody, Sorana Segal-Maurer, M.D.―the New York-Presbyterian Queens Hospital doctor who led the CAPELLA study for drugmaker Gilead Sciences―stated, “Finally, patients with drug-resistant HIV who can’t get to undetectable have an opportunity to achieve viral suppression, which is a tremendous achievement. It’s very dramatic to show someone their undetectable viral load for the first time in years and to see their CD4s rise, because those things are associated with a reduction in [AIDS-defining] opportunistic infections as well as an anticipated reduction in the risk of comorbidities like cardiovascular disease, renal [kidney] disease, and cancers.”

Mark Harrington, the longtime head of Treatment Action Group, who is also living with HIV, called the announcement “good news for people with multidrug-resistant HIV,” but pointed to Sunlenca’s $42,250 sticker price and wondered if it would be difficult for providers to get insurers to cover it―even in cases where it was clearly needed.

The drug is too new on the market for many patients even to ask that question at this point, though a Gilead representative confirmed that Sunlenca will be included in the company’s patient assistance program for those who are un- or underinsured, or who hit coverage snags.

What Other Purpose Could Sunlenca Serve?

According to Jared Baeten, M.D., Gilead’s vice president of HIV clinical development, the company is also currently testing Sunlenca as a drug for the overall HIV population, investigating it alongside two so-called broadly neutralizing antibodies (bNAbs) as a possible twice-yearly injection—some data on that will come out later this year, he says—and alongside the Merck drug islatravir (the two pharmaceutical companies are collaborating) as a possible weekly oral pill.

Additionally, Gilead is running two versions of the so-called PURPOSE trial (one for cisgender women and one for cisgender men and trans people who have sex with partners assigned male at birth) in several countries to see if Sunlenca alone, like ViiV’s Apretude (cabotegravir), could work as a long-acting injectable for PrEP as HIV prevention.

Baeten says the hope is that Sunlenca will only require a subcutaneous (just beneath the skin) injection rather than the into-the-butt, intramuscular injection required of Apretude. Gilead, he says, is also looking into whether the injection could be self-done at home rather than require a doctor’s visit because some people have communicated to the company that they would prefer to self-inject.

But Harrington wonders how successful Sunlenca could be for mainstream (non–multidrug-resistant) HIV treatment or for PrEP given that, per what he hears, existing injectables for treatment and PrEP (Cabenuva for treatment and Apretude for PrEP) have not had high uptake since they were approved in recent years. That’s presumably because many people living with HIV or who use PrEP are fine with oral options and/or because insurers won’t cover injectables unless absolutely necessary given their very high cost. Apretude, for example, has a sticker price of about $22,000 annually, compared to about $400 annually for generic oral PrEP.)

He speculates that an injectable HIV treatment regimen of Sunlenca plus two bNAbs could cost as much as $150,000 annually—versus the roughly $36,000 to $48,000 for most current one-pill-daily HIV regimens—because bNAbs (such as the cancer agent Abraxane) are wildly expensive. “Would that be affordable enough to make a difference in the real world?” he asks.

For now, though, people living with highly drug-resistant HIV have a new promising option to get to undetectable viral load (and hence make their HIV untransmittable to others sexually), possibly raise their CD4s, and enjoy overall better health and longevity. We’ll follow up on Sunlenca’s use in such folks in about a year, when we’ll better know if the positive trial outcomes extend to users “in the real world”—as well as how willing insurers are to cover it if shown by providers that their patients have few or no other choices.

By Tim Murphy