GlaxoSmithKline’s HIV prevention injectable Apretude threatens Gilead with FDA blessing. But will doctors use it?

GlaxoSmithKline GSK House in Brentford, UK
For the initial launch of the first long-acting injectable for HIV prevention, GSk's ViiV will target people who’re already taking a daily PrEP pills. (GlaxoSmithKline)

After making history with the first complete long-acting regimen for the treatment of HIV, GlaxoSmithKline’s ViiV Healthcare has now made a component of that therapy into a preventative option, threatening a major franchise at Gilead Sciences.

On Monday, the FDA blessed GSK’s Apretude, or cabotegravir, to reduce the risk of sexually acquired HIV. The endorsement provides users the first long-acting injected option in the pre-exposure prophylaxis (PrEP) setting.

With that, Apretude will go up against Gilead’s well-established Truvada and its generic, plus the California biotech’s newer Descovy. Unlike those daily pills, Apretude is administered once every two months after the loading doses. The drug has shown stellar efficacy in two phase 3 trials, topping Gilead’s daily pill Truvada in both men and women at preventing HIV infections.

ViiV is offering Apretude at the wholesale acquisition cost of $3,700 per vial, a company spokesperson told Fierce Pharma. Given its bimonthly dosing, Apretude costs about the same or less than branded oral PrEP options.

Before the PrEP nod, cabotegravir and Johnson & Johnson’s rilpivirine won an FDA go-ahead in January as Cabenuva to treat patients infected with HIV. Citing strong patient demand for long-acting options in HIV, GSK thinks the cabotegravir franchise could reach over £2 billion in sales in 2026.

That’s an ambitious goal considering Cabenuva only sold £18 million in the first nine months of 2021. But ViiV believes the franchise is only beginning to take off.

RELATED: GlaxoSmithKline's long-acting HIV drug nabs FDA priority review as a preventative option

Launching a physician-administered injectable during COVID-19 has been a challenge, ViiV CEO Deborah Waterhouse acknowledged in an interview. Nearly 3,000 U.S. patients have been treated with Cabenuva, and the drug has captured about 4% of U.S. new-to-brand market share, she said.

Since doctors treating HIV aren’t necessarily familiar with the workflow of giving injections, ViiV has run several studies to understand how to implement the process for administering an injectable. The company has spent most of the year partnering with clinics and healthcare delivery networks to straighten out that process, Waterhouse said.

Now, the “setup phase” is over, Waterhouse said, and ViiV is in a “business as usual” phase.

That preparation for Cabenuva will pay off for Apretude, but Waterhouse said the new PrEP offering will likely experience a similar slow ramp in its first year on the market.

As ViiV’s R&D chief Kimberly Smith pointed out, Apretude is looking at an expanded group of doctors compared with Cabenuva's prescriber base because those who write scripts for PrEP aren’t always HIV doctors.

For the initial launch, ViiV will target people who’re already on PrEP. After the company secures reimbursement and smooths the process, it will expand into populations that have the highest numbers of HIV infections. Several counties with high rates of HIV infection among Black men and Latinx men will be ViiV’s focus, Waterhouse said.

That could be a large market; the CDC estimates that only a quarter of the 1.2 million people who would benefit from a PrEP drug are actually on one, and those who are already on it are disproportionately white males, Smith noted.

RELATED: GSK's ViiV, under threat from Gilead-Merck collab, eyes 'ultra-long-acting' HIV drugs with Halozyme deal

GSK’s £2 billion market estimate in the cabotegravir franchise is rooted in people’s preference to not have to keep HIV medication in their house and for less frequent dosing. Apart from the stigma, people often forget to take their PrEP medication or don’t take the pills as required, potentially lowering the efficacy.

“We know from our market research that people want something that they can just do discreetly and forget about it,” Waterhouse explained.

But industry watchers question whether £2 billion is attainable as both Cabenuva—now approved in a monthly dosing schedule—and Apretude require more frequent doctor visits.

Despite the obvious burden of daily pills, “we still believe that most patients will find the daily pill approach convenient and flexible and are unlikely to switch to injectables, particularly if they are still physician office-administered,” SVB Leerink analyst Geoffrey Porges wrote in a November note to clients. Patient awareness, perceived convenience of injection and payer coverage will shape the market for Apretude, he said.

Doctors are willing to make changes according to patients’ demands, Smith said. Some large clinics made a conscious decision to put a system in place to manage the demand for HIV injectables. ViiV is conducting another implementation study that’s looking at alternative sites of administration to take some of the burden off the clinics, Smith noted. Eventually, ViiV will evaluate people getting their doses at pharmacies to make access easier.

To reflect Apretude’s target population, ViiV mandated that 50% of U.S. participants in its phase 3 trial in men be Black. The fact that the trial met that goal is “an illustration that those folks are absolutely willing to take PrEP—you just have to get the information to them and make it available to them,” Smith said.

RELATED: Merck's HIV program suffers 6 full, 7 partial clinical holds from FDA

Still, £2 billion is only a small fraction of where Gilead’s HIV business is at today. Looking forward, a self-administered option with longer injection gaps could grow the franchise even more, Waterhouse said.

Toward that goal, ViiV recently partnered up with Halozyme Therapeutics, using the latter’s ENHANZE drug delivery technique to prolong the dosing intervals for Apretude. Early proof-of-concept data from the platform are expected next year.

ViiV is not the only one targeting long-acting HIV therapies. But Merck & Co., in a collaboration with Gilead, suffered a major setback recently with its efforts. The FDA placed several trials of the New Jersey pharma’s islatravir on hold, including a long-acting formulation for PrEP, after investigators observed decreases in total lymphocyte and CD4 T-cell counts in some patients who got the drug.