GSK's long-acting HIV injectable, Cabenuva, finally snags its FDA green light

GlaxoSmithKline GSK House in Brentford, UK
GlaxoSmithKline's ViiV Healthcare has won FDA approval for Cabenuva, the world’s first complete long-acting HIV regimen. (GlaxoSmithKline)

Over a year after an FDA rebuff, GlaxoSmithKline’s ViiV Healthcare has finally won U.S. clearance for an injectable drug that could relieve HIV patients of the trouble of taking daily pills.

The FDA today greenlighted Cabenuva, the world’s first complete long-acting, injectable HIV regimen, for patients who are already virologically suppressed. While standard antiretroviral medication is taken daily, Cabenuva is injected once a month.

Being able to cut dosing frequency from 365 times per year to once a month could be life-changing for HIV patients, ViiV’s head of R&D, Kimberly Smith, M.D., said in an interview.

In fact, nine out of 10 participants in the pivotal Flair trial preferred long-acting Cabenuva to their daily oral treatment at Week 48. Still, those are patients who volunteered for a clinical trial of a long-acting HIV regimen. In the real world, ViiV expects most people will stick to their existing once-daily oral treatments, CEO Deborah Waterhouse said. To her, Cabenuva offers a choice for a niche but important patient group.

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“We know that there’s a proportion of people who’re living with HIV who really struggle to take a tablet every day, either because they just find it stigmatizing and very challenging that it reminds them that they are living with HIV,” Waterhouse said.

“Some people have the real issue with the disclosure that they’re HIV positive, so they need to hide their medication away and live in fear that that medication will be found,” Waterhouse added. “Others really struggle to adhere.”

Cabenuva was originally expected to snag its U.S. nod by the end of 2019, but the FDA rejected it because of manufacturing problems. Since then, Cabenuva got its global-first approval in Canada in March 2020. In December, the regimen was authorized in EU under two separate brand names.

A combination of ViiV’s cabotegravir and Johnson & Johnson’s Edurant, Cabenuva has two sets of phase 3 data showing it works as well as commonly used oral meds at suppressing HIV. In the Atlas study, 92.5% of patients had undetectable viral loads after 48 weeks of treatment with Cabenuva, while 95.5% on traditional three-drug regimens achieved that benchmark.

In the Flair trial, the injectable’s 48-week virologic suppression rate hit 93.6%, as ViiV’s own therapy Triumeq (abacavir/dolutegravir/lamivudine) reached 93.3%. Updated data showed 86.6% of Cabenuva users still had no detectable viral load at 96 weeks, versus 89.4% for those who received Triumeq.

Before Cabenuva, all HIV regimens were taken once daily. TaiMed Biologics’ antibody drug Trogarzo is given intravenously once every 14 days, but it needs to be used alongside other antiretroviral meds and is only meant for a small group of patients resistant to multiple treatments.

ViiV is aiming to win FDA approval to cut the dosing frequency further, too—a feat it already achieved in Europe thanks to an extra data submission.

Some of the Atlas participants rolled over into the Atlas-2M trial, which showed similar virologic nonresponse rates between once-monthly and bimonthly Cabenuva at Week 48. ViiV plans to immediately submit the data for a bimonthly schedule with the FDA, Smith said.

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As COVID-19 rages on, it’d be difficult for ViiV to roll out a new injectable drug that’s administered by a healthcare professional for a group of patients who already have compromised immune systems. Smith noted that in Cabenuva’s clinical trials, investigators have been able to manage the pandemic situation by bridging participants with orals if they can’t come into the clinic.

But both Smith and Waterhouse acknowledged that overall HIV drug switching has slowed during the pandemic. ViiV’s seeing U.S. switching down by roughly 40% from pre-pandemic levels, with the company’s new-to-brand share at around 4,000 a week for the last nine months, Waterhouse said.

Cabenuva marks GSK’s latest effort at broadening its HIV portfolio. Besides Cabenuva, it has two-drug regimens Dovato and Juluca trying to steal share from traditional triplets and establish a new treatment standard. Right now, Gilead Sciences’ Biktarvy is the best-selling HIV treatment with $5.19 billion of sales in the first nine months of 2020. By contrast, GSK’s entire HIV portfolio brought in £3.61 billion (4.89 billion) during the same period.

ViiV’s also advancing the cabotegravir component in Cabenuva as a challenger to Gilead’s monopoly in the HIV prevention field, or PrEP. The ViiV drug, given every two months, has shown superior efficacy over Gilead’s daily Truvada in both men and women in late-stage trials.