FDA Approves Nirogacestat for Treatment of Desmoid Tumors

SpringWorks Therapeutics announced late today that the FDA has approved nirogacestat, which the company says is the first therapy available to treat adult patients with progressing desmoid tumors who require systemic treatment. The therapy, an oral gama secretase inhibitor, will be marketed as Ogsiveo, the company announced in a statement.

The FDA previously granted breakthrough therapy, fast track, and orphan drug designations to nirogacestat for the treatment of desmoid tumors, according to the company’s statement.

The agency commented on the announcement in a separate statement.

“The FDA continues to address unmet medical need and advance the development of safe and effective therapies for the millions of Americans whose lives are affected by rare tumors,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Desmoid tumors are rare tumors that can lead to severe pain and disability. Today’s approval will offer the first approved treatment option for patients beyond surgery and radiation.”

According to the Mayo Clinic, desmoid tumors are noncancerous growths that appear in connective tissue, most often on the arms, legs, and abdomen. Some do not require immediate treatment because they are slow growing, while others are aggressive and must be treated with surgery, radiation, or chemotherapy to keep them from growing into nearby organs, which can make them life threatening. They can cause pain and disfigurement, and they can reduce functioning and quality of life.

Even though desmoid tumors are not considered cancers, because of their behavior, they may be treated by oncologists.

Saqib Islam, CEO of SpringWorks

Image credit : SpringWorks Therapeutics

“Our team is honored to deliver the first FDA-approved therapy for patients with desmoid tumors. This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” Saqib Islam, CEO of SpringWorks, said in the statement. “We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe [nirogacestat] has the potential to become the new standard of care for people living with these devastating tumors.

“This is a watershed moment for the desmoid tumor community and we would like to extend our gratitude to the patients, families, investigators, and advocacy groups involved in the journey to making [nirogacestat] available in the US.”

Approval was based on the results from the phase 3 DeFi trial, published in the March 2023 New England Journal of Medicine. The phase 3 international, multicenter, randomized, double-blind, placebo-controlled trial (NCT04785964) evaluated the drug in 142 adults with progressing desmoid tumors not amenable to surgery.

Patients enrolled in the trial received 150 mg of nirogacestat or placebo orally, twice daily, until disease progression or unacceptable toxicity. Overall, 77% of patients in the trial had received previous treatment.

Nirogacestat met the primary end point of improving progression-free survival (PFS) and demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (HR, 0.29; 95% CI, 0.15-0.55); P < .001). Among other results:

• Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm
• Confirmed objective response rate (ORR) based on RECIST v1.1 was 41% with nirogacestat vs 8% with placebo (P < .001); the complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm
• The median time to first response was 5.6 months with nirogacestat and 11.1 months with placebo
• PFS and ORR improvements favored nirogacestat across subgroups, including tumor location and treatment status
• Nirogacestat demonstrated early and sustained improvements in patient-reported outcomes, including pain, desmoid tumor–specific symptoms, physical functioning, and overall health-related quality of life.
• The most common adverse events, affecting at least 15% of patients, were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea

The company is also evaluating the nirogacestat for a rare subtype of ovarian cancer, with a phase 2 trial expected to be conducted in the second half of 2024.