RARE Daily

FDA Accepts IND and Grants Priority Review for SpringWorks Desmoid Tumors Therapeutic

February 27, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has accepted for Priority Review SpringWorks Therapeutics’ New Drug Application for nirogacestat, an investigational gamma secretase inhibitor, for the treatment of adults with desmoid tumors.

Desmoid tumors are rare, aggressive, locally invasive, and potentially morbid tumors of the soft tissues. While they do not metastasize, desmoid tumors are associated with a high rate of recurrence. Sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis, these soft tissue tumors can be serious, debilitating, and, in rare cases when vital structures are impacted, they can be life-threatening. Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females. It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States. Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery. There are currently no FDA-approved therapies for the treatment of desmoid tumors.

The application has been given a Prescription Drug User Fee Act (PDUFA) action date of August 27, 2023. The FDA’s Priority Review designation is given to investigational medicines that treat a serious condition and offer significant improvements in safety or effectiveness. In addition, the FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application.

“People with desmoid tumors can experience severe pain and other debilitating morbidities,” said Saqib Islam, CEO of SpringWorks. “The acceptance of our NDA for nirogacestat with Priority Review represents a significant milestone in our ambition to provide the first approved therapy for patients with desmoid tumors.”

The NDA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program and is based on the previously announced positive results from the phase 3 DeFi trial, a global, randomized, double-blind, placebo-controlled trial evaluating nirogacestat in adult patients with desmoid tumors.

The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi includes an open-label extension phase, which is ongoing.

The FDA granted Fast Track and Breakthrough Therapy designations to nirogacestat for the treatment of adult patients with progressive, unresectable, recurrent, or refractory desmoid tumors or deep fibromatosis. Nirogacestat has also received Orphan Drug designation from the FDA for the treatment of desmoid tumors.

Photo: Saqib Islam, CEO of SpringWorks

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