The FDA has added to the woes already troubling Merck's HIV portfolio by slapping 13 clinical holds on its broad-based program for the confounding disease.
The latest hurdle involves six full clinical holds across the entire clinical development lifespan and seven partial holds across mid- and late-stage studies of the investigational compound islatravir. Merck disclosed the trial holds Monday after market close.
HIV treatments have long befuddled scientists, but this latest move is a broad-based swipe at Merck's attempt to develop new HIV treatments. Islatravir is being studied in multiple populations in various combinations and as a solo med. In a sign of how significant the news is: seven of the 13 holds are phase 3 trials.
The FDA's sweeping action impacts oral and implant formulations of islatravir for HIV-1 pre-exposure prophylaxis, more commonly known as PrEP; the injectable formulation of islatravir for HIV-1 treatment and prophylaxis; as well as the oral, once-daily combination of islatravir with Merck's Pifeltro.
The New Jersey Pharma said the FDA's decision was based on decreases in total lymphocyte and CD4+ T-cell counts in some patients who received islatravir, which was previously disclosed. Those decreases led Merck to pause development of a mid-stage study last month and two late-stage ones earlier this month.
No new studies will be initiated and participants currently receiving islatravir will be cut off from the drug and instead given approved PrEP meds. Participants in the islatravir/Pifeltro combo study will continue to receive the therapy, but no new patients will be let into the trial.
Of the six full clinical holds, two of the trials had not yet opened enrollment, including a phase 2 PrEP study in transgender and gender diverse patients and a phase 2a PrEP study looking at a once-yearly islatravir implant in people at low risk for HIV-1 infection.
The partial clinical holds impacted three fully enrolled trials, including two phase 3 studies. The FDA's ClinicalTrials.gov database lists 18 ongoing studies featuring islatravir, including four that have been completed.
It doesn't end there: Merck and Gilead have now decided to stop dosing patients in a phase 2 study testing islatravir in an oral weekly combo with Merck's investigational med lenacapavir in people with HIV who are virologically suppressed on antiretroviral therapy. The two pharmas put a hold on enrollment in the study last month after having only begun in October.
Patients in the islatravir/lenacapavir trial will switch back to their previous antiretroviral regimen while the companies consider whether a different dosing plan for the combo may work as a once-weekly oral therapy.
"Gilead and Merck remain committed to the collaboration," the statement said.
Merck and Gilead are among the leading pharmaceutical companies looking to bring new treatments to an epidemic that has lingered for 40 years. HIV/AIDS killed 680,000 people in 2020, and 37.7 million people worldwide are living with HIV as of June 30, according to the United Nations. Of those, 28.2 million people were accessing antiretroviral therapy.
Aside from Merck and Gilead, other HIV drugmakers include GlaxoSmithKline's ViiV Healthcare and Excision BioTherapeutics, which is set to test its CRISPR-based therapy in humans soon. Overall, ClinicalTrials.gov lists 170 studies of HIV-1 meds that are currently recruiting, enrolling or active.