FDA Places Partial Hold of Foghorn Study in Synovial Sarcoma

Foghorn Therapeutics Provides an Update on FHD-609

Rare Daily Staff

Foghorn Therapeutics said it is pausing enrollment in the study of its experimental therapy FHD-609 to treat the rare cancer synovial sarcoma after the U.S. Food and Drug Administration place a partial clinical hold on the study because of potential cardiac risks.

Synovial sarcoma is an often-aggressive soft tissue sarcoma that originates from different types of soft tissue, including muscle or ligaments. Synovial sarcoma can occur at any age but is most common among adolescents and young adults. It represents around 5-10 percent of all soft tissue sarcomas, with approximately 800 new cases each year in the United States. Surgery remains the most effective treatment for synovial sarcoma, and there are limited therapeutic treatment options.

FHD-609 is a potent, selective, intravenously administered protein degrader of BRD9, a component of the ncBAF complex. Preclinical studies have demonstrated tumor growth inhibition in synovial sarcoma, a cancer genetically dependent on BRD9. Almost all synovial sarcoma cancers contain mutations that render the cancer genetically dependent upon BRD9, what is commonly referred to as a synthetic lethal relationship.

The FDA partial hold came after a patient with synovial sarcoma in the second highest dose experienced a grade 4 QTc prolongation event. It reflects a change in the electrical activity of the heart and can have serious consequences.

The company said patients in the affected cohort had their doses reduced and additional safety measures have been discussed with and provided to the study investigators. The company said it promptly communicated the enrollment pause and risk mitigation actions to the FDA and European regulatory authorities.

Consequently, the FDA placed the study on partial clinical hold in the United States, while allowing patients currently enrolled and benefiting from therapy to continue dosing and to remain on FHD-609. The company said it is not at this time planning to pursue a dose expansion study independently.