Foghorn muted again as FDA places partial clinical hold on 2nd cancer drug trial

As Foghorn Therapeutics battles to free a trial from an FDA clinical hold, the biotech is now facing a partial hold for another program—meaning the company's two clinical assets are now tied up in red tape.

This time it's FHD-609, Foghorn’s protein degrader that was being investigated in a phase 1 dose escalation trial in synovial sarcoma and SMARCB1-deleted tumors. The company paused enrollment in the study after one synovial sarcoma patient who received the second highest dose suffered a grade 4 QTc prolongation event, a form of irregular heartbeat, the biotech said in a release April 24.

On being informed, the FDA placed the trial on partial clinical hold, with participants already receiving the drug allowed to continue on their therapy.

Enrollment in the dose-escalation portion of the study has already been completed, and Foghorn had identified a maximum tolerated dose, the company said. Other patients in the same cohort as the affected patient have now had their dose reduced and additional safety measures have been introduced and communicated to the FDA.

FHD-609 is an intravenously administered degrader of BRD9, a protein that synovial sarcoma cells rely on for survival. The phase 1 trial was expected to enroll up to 104 patients, with initial safety and efficacy data due in mid-2023.

The news hit the biotech’s shares, which were down 23% at $5.18 in premarket trading Monday from a Friday close of $6.72. Foghorn’s stock had followed the industry trend of a positive trajectory in recent weeks, recovering ground lost when the shares hit a nadir of $4.70 apiece in late March.

Another of the cancer-focused company’s meds, an enzyme inhibitor called FHD-286, has remained under an FDA hold since May over suspected cases of fatal differentiation syndrome in a phase 1 trial for advanced acute myelogenous leukemia and myelodysplastic syndrome. The partial hold was expanded to a full clinical hold in August as more cases came to light.

Differentiation syndrome is when the body is flooded with cytokines released by leukemia cells that anti-cancer drugs target. Foghorn said last year that it’s an effect “that has been seen with, and is believed to be on-target for, the proposed mechanism of action for FHD-286.”

However, a dose-escalation study of FHD-286 in metastatic uveal melanoma remains ongoing, with initial safety and efficacy data expected in the first half of the year.

Despite the tough news for FHD-609 and FHD-286, the company’s only clinical-stage assets, at least Foghorn doesn’t have the same financial pressures as many of its more cash-strapped peers. The biotech ended last year with $345.8 million in cash, equivalents and securities, which is expected to last into the second half of 2025.

The company has collaborations with both Merck & Co. and Eli Lilly’s Loxo Oncology unit, as well as a recently disclosed selective EP300 degrader targeting CBP mutant cancers.