No holiday gift for GSK: FDA sends long-acting HIV injectable back to work

HIV patients looking for relief from the burden of daily pills will have to wait a little longer.

Saturday, GlaxoSmithKline’s ViiV Healthcare said that the FDA had rejected its long-acting HIV injection, known under the working title Cabenuva. The statement is thin on details, noting only that the complete response letter is related to chemistry manufacturing and controls (CMC), which is about data generated for the manufacturing process and product testing

A ViiV spokesperson confirmed to FiercePharma that the FDA’s concerns do not include the need to generate more clinical data but declined to provide more details. The company said it would “work closely with the FDA to determine the appropriate next steps” for the application.

The drug is composed of GSK’s integrase strand transfer inhibitor cabotegravir and Johnson & Johnson’s non-nucleoside reverse transcriptase inhibitor rilvipivirin, sold as Edurant in its tablet form. The GSK component is being produced at the company's Barnard Castle factory in the U.K., the spokesperson said.

While existing HIV antiretroviral therapies require patients to take daily medications to control the virus, the new combo would allow them to receive an injection in the muscle once a month. Reduced dosing frequency could help allay the fear of forgetting a dose and improve compliance.

In two phase 3 studies, Cabenuva showed it could match up to standard-of-care, daily, oral three-drug regimens at suppressing HIV. In the Atlas study, the drug successfully contained the virus in 92.5% of patients after 48 weeks, while 95.5% of those on a three-drug regimen had undetectable viral loads. 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%. 

Traditionally, a complete HIV regimen contains three ingredients. GSK is aiming to reduce the number of drugs HIV patients need to take, having already brought to market dual-drug regimens Juluca and Dovato. Juluca combines GSK’s integrase inhibitor Tivicay (dolutegravir) and Edurant and is approved to treat patients already virally suppressed. Dovato, currently approved for treatment-naïve adults, uses Tivicay and widely used off-patent lamivudine.

In Cabenuva's Flair and Atlas trials, investigators observed high rates of injection site reaction. But execs have stressed that most events were manageable and led to very few patient withdrawals from the trial.

In its Saturday statement, the GSK unit said the CMC problem is not related to safety and that there’s been no change to the safety profile of the drug seen in clinical trials. ViiV is currently following both trials for longer periods.

RELATED: 2-month HIV injection could be on its way, as ViiV touts new dual-drug win

Meanwhile, it’s running the Atlas-2M study, which is testing the drug through bimonthly injections. That phase 3 trial recently reported positive results, showing comparable efficacy between the two dosage forms.

ViiV has other HIV drug applications before the FDA, including for a children-friendly version of dolutegravir and one for fostemsavir, a first-in-class attachment inhibitor for adults with multidrug-resistant HIV.

Still, GSK’s goal of challenging Gilead Sciences’ lead in the HIV market is largely dependent on the success of two-drug regimens. So far, it has yet to pick up significant steam against Gilead’s fast-growing Biktarvy. In the first nine months, Gilead grew HIV sales by 12.3% year over year to $11.86 billion, and GSK’s £3.60 billion ($4.69 billion) only represented a 1% increase.

Editor's Note: The story has been updated with additional response from ViiV Healthcare.