For the second time in the past year, the FDA has paused a clinical trial for a Foghorn Therapeutics cancer drug after the report of a serious complication.
The partial clinical trial hold announced Monday is for FHD-609, a drug in development for treating a soft tissue cancer called synovial sarcoma as well as tumors characterized by the loss of a protein called SMARCB1. The drug from Cambridge, Massachusetts-based Foghorn is a protein degrader designed to leverage a cellular mechanism for disposing of proteins. It is administered as a twice-weekly intravenous infusion.
FHD-609 had completed the dose-escalation part of its Phase 1 study, which was designed to identify the maximum tolerated dose or the recommended dose to advance to Phase 2 testing. Foghorn said a maximum tolerated dose had been identified. The adverse event was reported in a synovial sarcoma patient who received the second-highest dose. Foghorn said this patient developed an irregular heart rhythm problem called QTc prolongation. This complication was described as grade 4, the most severe classification.
Foghorn disclosed nothing about the condition of the patient who developed the cardiac complication. But the company said other patients in that dose cohort had their dose of the drug reduced. The company said it has discussed additional safety measures with study investigators. The company notified U.S. and European regulators. The FDA placed a partial hold on the study, which halts the enrollment of new participants but permits already enrolled patients to continue receiving the experimental therapy.
Following the dose escalation part of the study, the clinical trial was designed to proceed to a dose expansion part to further evaluate FHD-609’s safety profile. Foghorn said it is not planning to independently pursue a dose expansion study at this time.
Last May, Foghorn disclosed a partial clinical hold on a different drug, a small molecule formulated as a once-daily pill code-named FHD-286. This Foghorn drug had reached Phase 1 testing in two blood cancers: acute myelogenous leukemia and myelodysplastic syndrome. The FDA partial halt followed the report of the death of a patient who may have experienced differentiation syndrome, an excessive immune response that is a known complication of leukemia therapies.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Last August, the agency placed the FHD-286 clinical trial under a full clinical hold, stopping dosing of all patients in the study. That hold remains in place. The FDA has asked Foghorn for more data about safety, risk mitigation, and clinical activity across dose levels.
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