FDA Places Hold on Gilead HIV Trials Over Vial Quality Concerns

The U.S. Food and Drug Administration (FDA) placed a clinical hold on Gilead Sciences’ use of injectable lenacapavir in borosilicate vials in all ongoing clinical studies for HIV and HIV pre-exposure prophylaxis (PrEP). There are emerging worries about the compatibility of vials manufactured of borosilicate glass with lenacapavir solution and concerns that it will cause the formation of “sub-visible” glass particles in the mixture.

Ten studies are halted completely. Oral formulations of the drug will continue. Gilead stated that it is confident about the future of the drug’s potential and is working to resolve the vial quality issue.

Screening and enrollment of participants and dosing of the injectable lenacapavir will be allowed in any studies of lenacapavir. All other activities associated with the studies, including patient monitoring and dosing in the comparator arms, will continue per study protocols.

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The hold applies to 10 studies:

• The Phase II/III GS-US-200-4624 study of the safety and efficacy of long-acting capsid inhibitor GS-6207 in combination with an optimized background regimen in heavily treated patients living with HIV-1 with multidrug resistance.

• The Phase II GS-US-200-4334 study, an open label, active control trial of GS-6207 in combination with other antiretroviral agents

• The Phase I GS-US-200-5709 study in healthy participants for safety, tolerability and pharmacokinetics of lenacapavir.

• The Phase III GS-US-412-5624 trial of twice yearly long-acting subcutaneous lenacapavir and daily oral emtricitabine/tenofovir/alafenamide for PREP in adolescent girls and young women (PURPOSE-1).

• The Phase III GS-US-528-9023 trial of subcutaneous twice yearly long-acting lenacapavir for PREP in cisgender men, transgender women, transgender men, and gender non-binary people 16 years or older who have sex with partners assigned male at birth and at risk for HIV.

• The Phase Ib GS-US-536-5816 trial of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with lenacapavir in virologically suppressed adults with HIV.

• The Phase I GS-US-200-5710 study in healthy participants for subcutaneous and intramuscular lenacapavir.

• The Phase I GS-US-200-5717 study in healthy people of subcutaneous and intramuscular lenacapavir.

• The Phase I GS-US-528-5744 study to evaluate the pharmacokinetics and distribution of lenacapavir into rectal and female genital tracts tissues in HIV-Seronegative participants.

• The Phase I GS-US-200-4540 study of subcutaneous injection sites on the pharmacokinetics of lenacapavir.

“We are committed to working diligently with FDA to resolve this glass vial compatibility quality issue and resume injectable lenacapavir dosing in the affected studies in a timely fashion,” said Dr. Merdad Parsey, Chief Medical Officer, Gilead Sciences.

Lenacapavir is the company’s potential first-in-class long-acting HIV-1 capsid inhibitor being developed for the treatment and prevention of HIV-1 infection. The drug’s multi-stage mechanism of action is different from other approved classes of antivirals and is engineered for long-acting therapy options. It acts on the virus at multiple stages of the viral lifecycle.

Earlier this month, Gilead voluntarily recalled two lots of its COVID-19 antiviral Veklury (remdesivir) after customer complaints of glass particulates. The company at that time said there had been no reports of adverse events related to the recall. The risk statement noted, “The administration of an injectable product that contains glass particulates may result in local irritation or swelling in response to the foreign material. If the glass particulate reaches the blood vessels it can travel to various organs and block blood vessels in the heart, lungs or brain which can cause stroke and even lead to death.

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