Almost 500 days have gone by since Molecular Templates disclosed the second of two cardiac adverse events in recipients of its CD38-directed cancer candidate. The biotech dialed down the dose at the start of 2022, and the trial has progressed uneventfully since then.
Nonetheless, the FDA has now slapped a partial hold on the study and asked for information such as the justification for the revised dose. In November 2021, alarms began to sound about the safety of MT-0169, a treatment designed to deliver a toxin to cells that express CD38. At the time, the biotech reported (PDF) a grade 2 case of reversible myocarditis and a grade 3 case of nonischemic cardiomyopathy in quick succession.
Molecular Templates responded in January 2022 by slashing the MT-0169 dose from 50 mcg/kg to 5 mcg/kg. Since then, the biotech has treated four participants with the 5-mcg/kg dose and given the 10-mcg/kg regimen to three patients. No subjects have suffered cardiac adverse events at either of the doses. The only event above grade 1 was transient grade 2 diarrhea in one patient on the 10-mcg/kg dose.
Now, the FDA has put the study on partial clinical hold. According to Molecular Templates, the agency took the action based on the previously disclosed cardiac adverse events seen in two patients dosed at 50 mcg/kg. The FDA has asked for “narratives on the two patients who experienced cardiotoxicity at 50 mcg/kg, justification for the revised dose of 5 mcg/kg and data evaluating the clinical benefit-to-risk ratio seen with the lower doses.”
Molecular Templates is “confident in the benefit-risk profile of MT-0169 at these lower doses,” Roger Waltzman, M.D., chief medical officer, said in a press release. For now, the biotech is unable to enroll new patients but can continue to treat existing participants.
The partial hold is another setback to MT-0169’s development and a blow to the fragilely positioned Molecular Templates. Takeda’s Millennium Pharmaceuticals took the candidate into the clinic in 2019, but site activation and new patient enrollment stopped for months in 2020 because of COVID-19. In April 2021, Takeda decided to return the rights to Molecular Templates, which soon ran into the safety scare.
Molecular Templates has kept its faith in MT-0169 during a tricky time. Last month, the company named the asset as one of three drug candidates it will keep developing as part of a slimmed-down, cost-conscious pipeline. The biotech narrowed its pipeline and halved its head count amid concerns it may breach the terms of a loan and trigger an accelerated repayment process that could sink the business.