After a quality glitch scuppered multiple trials of an investigational HIV drug late last year, Gilead Sciences vowed to sort out the problem swiftly. Now, the drug also faces a hurdle on its path to approval.
Gilead’s application for long-acting HIV candidate lenacapavir has been derailed, with the company announcing Tuesday that the FDA has issued a complete response letter (CRL). The regulatory action hinges on chemistry manufacturing and controls (CMC) concerns tied to the compatibility of Gilead’s drug with the vials it’s stored in.
Back in December, the FDA slapped a clinical hold on 10 studies of injectable lenacapavir, flagging a risk that the borosilicate vials holding the drug could interact with lenacapavir to create “subvisible” glass particles, Gilead said at the time.
In response to the FDA's CRL, Gilead stated today that it will provide the FDA with a plan and data to use a different vial type.
The company's approval ask covers use of the drug as an injectable in heavily treatment-experienced patients with multidrug-resistant HIV-1 infection. Ongoing clinical trials are testing both the injectable and an oral version of the drug.
Gilead sent its lenacapavir application to the FDA in June 2021, snagging a priority review tag from the agency.
The studies swept up in December’s clinical hold range from early- to -late-stage development, including two phase 3s.
Dosing in lenacapavir’s more advanced studies happens every six months, which means Gilead has a chance to rectify its vial problem quickly enough to avoid having to give many patients an alternative treatment, RBC Capital Markets Brian Abrahams wrote in a note to clients late last year.
“We look forward to discussing this further with FDA over the coming months so that we can make this investigational new therapy available to people living with multidrug-resistant HIV as soon as possible,” Merdad Parsey, M.D., Ph.D., Gilead’s chief medical officer, said in a statement.
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Also in December, Gilead said it was recalling two lots of its COVID-19 antiviral Veklury, also known as remdesivir, after a customer complaint alerted the company to the presence of glass particulates in the injectable. After conducting its own investigation, Gilead said at the time that it wasn’t sure how the particulates emerged in the Veklury vials.
Gilead’s lenacapavir trial pause last year coincided with a separate clinical hold on Merck’s HIV prospect islatravir. The company received 13 clinical holds on islatravir, seven of which were phase 3 trials.
Merck said the FDA’s decision was based on concerns with white blood cell counts in patients who took the drug, rather than a quality issue like Gilead’s.