After FDA rejection, Gilead's long-acting HIV med Sunlenca snags first global nod

Nearly six months after an FDA rejection, Gilead Sciences’ next-generation, long-acting HIV med lenacapavir has picked up its first global approval in Europe.

The European Commission has cleared lenacapavir for use every six months alongside other antiretrovirals to treat adults with multidrug-resistant HIV infection for whom no alternative effective treatment is available, Gilead said Monday. The current regimen also requires a lead-in phase with oral lenacapavir before the patient gets the twice-yearly under-the-skin injection. Gilead will market the drug as Sunlenca in Europe.

The EU approval comes as Gilead plays catch-up with GSK’s ViiV Healthcare in the field of long-acting injectables, which are gaining attention because they offer patients more convenience than daily oral pills. GSK’s Cabenuva is currently available as a full HIV regimen that can be administered once every two months.

“Our goal is to deliver multiple long-acting options in the future, in the belief that this will make a fundamental difference in the journey to end the HIV epidemic,” Gilead CEO Dan O’Day said in a Monday statement.

Sunlenca is a first-in-class capsid inhibitor with a high barrier to viral resistance and no known cross-resistance to other existing HIV drug classes. A capsid is a protein shell that protects a virus’s genetic material.

In the phase 2/3 CAPELLA study, Sunlenca’s combination with an optimized background regimen helped 83% of heavily pretreated patients with multidrug-resistant HIV achieve undetectable viral load after one year of treatment.

Building on the tremendous success of Biktarvy, Gilead is banking on Sunlenca to serve as a cornerstone of its multibillion-dollar HIV franchise in the long term when other products such as Descovy lose patent protection.

But the drug’s development and regulatory pathway have featured setbacks. Powerful as it is, Sunlenca must still be paired with other HIV meds. So it doesn’t really help with convenience if other components in its combinations require more frequent dosing.

Gilead originally partnered with Merck & Co. to study lenacapavir with the latter’s nucleoside reverse transcriptase translocation inhibitor islatravir, which has shown promise as a long-acting implant. But that effort appeared to be a dead end after the Merck drug was put on clinical hold in December based on observed decreases in patients’ CD4+ T-cell counts.

Gilead has other long-acting candidates that could potentially replace islatravir on Sunlenca’s side, including two broadly neutralizing antibodies. But those are in early testing.

For its part, Sunlenca suffered a temporary clinical hold in December 2021 based on the FDA’s concerns that glass particles of the vial could shed into the drug solution. Vial-drug compatibility issues eventually led to an FDA complete response letter on the drug’s application earlier this year.

Gilead in June resubmitted lenacapavir’s application based on an alternative vial type. The FDA has assigned a new target decision date of Dec. 27, 2022. In addition, Gilead is evaluating lenacapavir single agent as an HIV PrEP option in the phase 3 PURPOSE 2 trial.

Meanwhile, Gilead’s and Merck’s setbacks are bolstering GSK’s position in the long-acting market. GSK’s two-drug regimen Cabenuva, which had its own manufacturing hiccup before an FDA go-ahead in early 2021, is slowly gaining traction as doctors set up infrastructure and processes to administer the drug. GSK’s ViiV has also teamed with Halozyme to potentially further extend the drug’s dosing interval beyond every two months.

GSK is also working on its own capsid inhibitors, VH4004280 and VH4011499, which just entered clinical testing.