The partial clinical hold follows Foghorn’s voluntary pause of the study and is due to one patient developing irregular heartbeat following treatment with FHD-609.
Pictured: Front of FDA headquarters/Al Drago/CQ Roll Call/Getty Images
The FDA has placed a partial clinical hold on a Phase I study of Foghorn Therapeutics’ investigational protein degrader FHD-609 after a patient developed a grade 4 QTc prolongation event, the company announced Monday.
The candidate is being developed for synovial sarcoma, a rare and aggressive tissue malignancy.
As per the FDA’s directive, enrolled patients who were benefiting from FHD-609 treatment will be allowed to continue dosing.
Foghorn first detected the case of irregular heartbeat and immediately paused enrollment into the Phase I study assessing FHD-609. As a safety measure, the company reduced the candidate’s dose in the affected cohort and discussed additional risk-mitigation procedures with the study’s investigators.
Foghorn also relayed the incident and its safety actions to the FDA and to European regulatory bodies, which prompted the clinical hold.
Administered intravenously, FHD-609 is a potent and selective degrader of the BRD9 protein, which forms part of the ncBAF complex and plays a role in the regulation of gene expression.
Recent studies have identified the potential of targeting the ncBAF complex in synovial sarcoma.
Prior to the partial hold, Foghorn had already completed the dose-escalation portion of the Phase I trial and had found a maximum tolerated dose. The study was also evaluating FHD-609 in tumors with a SMARCB1 genetic deletion.
At present, Foghorn is not planning to initiate a dose-expansion study of FHD-609, according to the press release.
More Trouble for Foghorn
With Monday’s partial hold, two of Foghorn’s clinical-stage development programs are now on hold.
In May 2022, the FDA ordered a partial clinical hold on the company’s Phase I study of FHD-286, an oral small molecule inhibitor of the BRG1 and BRM proteins. The pause followed a patient death due to differentiation syndrome, which at the time was deemed potentially related to the study drug.
In August, the regulator tightened its directive further to a full clinical hold after more suspected cases of fatal differentiation syndrome came to light.
Differentiation syndrome arises when leukemia cells all over the body rapidly release cytokines. This complication is an on-target adverse drug reaction for FHD-286, according to Foghorn.
The clinical hold for FHD-286 affects its study in acute myeloid leukemia and myelodysplastic syndrome. A Phase I study in uveal melanoma is ongoing.
The rest of Foghorn’s candidates are all in pre-clinical development.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com
