FDA slams GSK's monthly HIV injectable with CRL, citing manufacturing issues
HIV patients will have to wait a while longer for a long-acting viral suppression regimen as the FDA has rejected ViiV Healthcare’s NDA for the monthly injection of cabotegravir and rilpivirine.
Regulators handed the GSK subsidiary a complete response letter days before the original PDUFA date on December 29. While ViiV had been expecting a smooth sail to the finish line based on glowing clinical results, the CRL cited concerns with chemistry manufacturing and controls.
“There have been no reported safety issues related to CMC and there is no change to the safety profile of the products used in clinical trials to date,” ViiV added in a short statement.
A delay here with the monthly injection of cabotegravir and rilpivirine also means that ViiV will have to push back on the planned sNDA filing for the 2-monthly regimen, which was slated for the first quarter of 2020.
Gilead’s blockbuster cocktails, both doublets and triplets, have been immensely successful at keeping HIV to undetectable levels, but they have still left patients saddled with the burden of taking daily pills — which ViiV said is not only inconvenient but also carries an emotional burden. With their new formulation of their own experimental cabotegravir (integrase inhibitor) and J&J’s rilpivirine (non-nucleoside reverse transcriptase inhibitor), ViiV was looking to shake up the treatment landscape and carve out a bigger share from the Gilead-dominated market.
The long-acting regimen is designed for patients who are already virologically suppressed, have never experienced virological failures, and have not developed resistance to either of the ingredients. ViiV head of R&D Kim Smith has estimated that around 10% to 15% of all patients in the clinic would be candidates.
Two late-stage studies involving 1180 patients suggested that their injection was just as effective as standard antiretroviral therapy in virologic suppression, with similar rates of resistance at 1%. And as they follow up on a Phase IIb trial, researchers found that 83% of patients remain virally suppressed at the three-year mark.
That, alongside similarly positive data for the 2-monthly regimen, would have made a groundbreaking treatment option. The company said it’s working closely with the FDA to figure out the next steps.