FDA slaps partial hold on Epizyme’s lead drug; analysts say ‘don’t panic’

stop sign (knerri61/Pixabay)
New recruitment in the study is suspended, but patients already on treatment can continue on the drug. (knerri61/Pixabay)

Shares in Epizyme slipped in premarket trading today after the company announced a suspension of patient recruitment in a trial of its lead cancer drug after a patient developed a secondary lymphoma, but analysts at Jefferies are expecting the stock to bounce back.

The company says the FDA has implemented a partial clinical hold on its trials of tazemetostat, which means it cannot enroll new patients with genetically defined solid tumors and hematologic malignancies. Patients already taking the drug can, however, continue to receive it in the meantime, and enrollment outside the U.S. is currently unaffected.

The news has put pressure on Epizyme’s shares, which were down 12% this morning. Jefferies points out that several other companies have been in this situation—including Juno and Cellectis—and suggests the company will move quickly to “modify the protocol and trial brochures and get back up and running.” They anticipate a holdup of just a few months.

Tazemetostat is an inhibitor of EZH2, an enzyme which is overexpressed in multiple cancers and has been described as a “master switch” that helps malignant cells divide and proliferate. Epizyme is at the forefront of attempts to explore the role of the class in oncology, a little ahead of other players including Constellation Pharma which raised $100 million to advance its CPI-1205 candidate earlier this month.

The partial hold came after a patient in Epizyme’s pediatric phase 1 study with cancer of the skull/spine, who was receiving a higher dose of tazemetostat than is being tested in Epizyme’s phase 2 program in adults, developed a secondary T-cell lymphoma and had in fact shown a partial response to the drug.

“More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed across the tazemetostat clinical program,” says Epizyme.

The biotech’s published information shows that this type of cancer has been seen in animals exposed to tazemetostat, which Jefferies says could be behind the FDA’s cautious stance. However, as patients with this type of cancer typically undergo often undergo radiotherapy and aggressive chemotherapy, they are already at an increased risk of T-cell lymphoma, according to Jefferies, which notes that this type of cancer “is treatable with survival outcomes.”

They suggest that “based on preclinical data … and at least one case in patients here today, that any future potential label would probably have warning section or something on this—and this would not hamper the drug as the drug is for severe deadly cancers with no alternatives.”

Tazemetostat is being tested as a monotherapy in several phase 1 and 2 studies, including patients with epithelioid sarcoma, follicular lymphoma, diffuse large B-cell lymphoma (DLBCL) and mesothelioma, and is also in combination trials in DLBCL and non-small cell lung cancer (NSCLC).

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” says Robert Bazemore, Epizyme’s president and chief executive.