Gilead's HIV Drug Lenacapavir Receives FDA Complete Response Letter Over Manufacturing Concerns

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Recently, the U.S. FDA has issued a Complete Response Letter (CRL) regarding Gilead Sciences' lenacapavir, an HIV drug. In the CRL, the FDA identified Chemistry, Manufacturing, and Controls (CMC) issues related to the compatibility of the lenacapavir injection with the proposed glass vials.

FDA Questions Compatibility of Borosilicate Glass Vials with Lenacapavir Injection, Leading to Suspension of at Least 10 Clinical Trials. Gilead Sciences States Intent to Provide Comprehensive Plan and Corresponding Data Using Different Vials to Address the Issue.

Baird & Co. analysts wrote in a report to clients that the launch of lenacapavir may be delayed by a year due to the FDA's decision. Baird analyst Brian Skorney wrote in a March 1 report: "Given the FDA’s previous concerns about sub-visible glass particles in borosilicate vials used for injectable lenacapavir, this CRL is not entirely surprising. However, given Gilead's increasing emphasis on the upward potential of this program... we believe this update will make it temporarily difficult for management to drum up enthusiasm for the project."

Nevertheless, Skorney and his team believe that the negative outcome is only a "minor setback" for lenacapavir, and once Gilead resolves the production and quality control issues, the FDA will eventually approve the drug. On Tuesday morning, Gilead Sciences' stock price remained relatively unchanged, which may reflect that investors were already prepared for the FDA's rejection.

Gilead Sciences officially applied for FDA approval last summer, following positive results from a Phase 3 clinical trial. The trial involved multidrug-resistant (MDR) HIV-1 infected individuals who had previously tried available therapies that were no longer effective. In the trial, lenacapavir, administered subcutaneously every six months, was combined with an optimized background regimen. Data showed that lenacapavir effectively suppressed the virus, with approximately 80% of treated patients achieving undetectable viral loads (virologic suppression, HIV-1 RNA <50 copies/mL) after six months of treatment.

The trial tested both injectable and oral lenacapavir, and the data submitted to the FDA included approval applications for each formulation. Gilead spokesperson Brian Plummer noted that while the vial issue is specific to the injectable formulation, the oral tablets are used as part of the treatment initiation.

Plummer wrote in an email to BioPharma Dive: "Therefore, for this submission, the approval of the lenacapavir tablet depends on the approval of the lenacapavir injection."

For some time, the company has been emphasizing that lenacapavir is one of its most important drug projects. The drug is a long-acting HIV-1 capsid inhibitor that suppresses HIV-1 replication by interfering with multiple critical steps in the virus's life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, viral assembly and release, and the formation of the capsid core.

Unlike HIV drugs currently on the market, lenacapavir has a unique method of inhibiting HIV replication. Moreover, if approved, it will be the only HIV drug administered once every six months, significantly less frequent than currently available treatments.

Therefore, Wall Street has high hopes for lenacapavir. According to Mizuho Securities, industry analysts unanimously believe that by 2030, the drug's sales may exceed $1.1 billion.

Reference Source: FDA Rejects Gilead's Closely Watched HIV Drug