FDA approves Pfizer spinout SpringWorks' Ogsiveo as first treatment for disfiguring rare tumor type

Thanks to a new FDA approval, patients with ultra-rare desmoid tumors now have an FDA-approved treatment.

The FDA has greenlighted Ogsiveo, or nirogacestat, to treat desmoid tumors, which are marked by noncancerous soft tissue growths that often cause severe pain and disfigurement. The drug is made by SpringWorks Therapeutics, which spun out of Pfizer in 2017 with a portfolio of rare disease candidates.

Ogsiveo marks SpringWorks’ first commercial product, and it’s the first drug specifically approved for desmoid tumors.

Desmoid tumors are diagnosed in about 3 to 5 people per million a year. Patients may undergo a “barrage of treatments,” including surgery, chemotherapies, radiation and tyrosine kinase inhibitors, but recurrence rate remains high, SpringWorks CEO Saqib Islam said in an interview ahead of the approval.

Ogsiveo showed its efficacy in the phase 3 DeFi trial conducted in 142 patients, including 77% who had received previous treatment. Compared with placebo, Ogsiveo lowered the risk of disease progression or death by 71%.

At the 10th cycle of treatment, Ogsiveo showed significant benefits over placebo with respect to pain and certain disease-related measurements. But the drug was linked to a higher rate of diarrhea, nausea, sore mouth, rash and other side effects, with 42% patients having their dose reduced because of adverse events.

Based on the trial data, about 90% of clinicians would recommend their desmoid tumor patients switch to Ogsiveo, Islam said. In addition, more than 90% of doctors would be willing to search for new patients who aren’t currently getting treatment for the disease.

By SpringWorks’ estimate, about 1,000 to 1,650 new cases of desmoid tumor could be diagnosed per year in the U.S. About 6,000 to 7,000 patients in the country are currently receiving active interventions, and even more patients aren’t getting treated for various reasons, including concerns of treatment effects.

“I think we’ve got a meaningful opportunity in any of these three categories,” Islam said.

An oral gamma secretase inhibitor, Ogsiveo was originally developed for breast cancer. But Shivaani Kummar, M.D., who was then leading early clinical trial development at the National Cancer Institute, saw promising data for the drug in desmoid tumors from a phase 1 basket trial. Kummar later conducted a phase 2 trial, and those results prompted SpringWorks to pursue further development after the Pfizer spinoff.

SpringWorks’ new drug application for Ogsiveo earned the FDA’s priority review and was evaluated under the agency's Real-Time Oncology Review pathway, which allows for simultaneous data submission and regulatory assessment. To reach this point, SpringWorks earlier this year navigated a Form 483 from the FDA centered on a clinical data entry problem that was later resolved, plus a three-month delay after the FDA required more time to review additional analyses of data provided by the company.

The Connecticut biotech is also evaluating Ogsiveo for a rare subtype of ovarian cancer called granulosa cell tumors, with a phase 2 trial expected to read out in the second half of 2024, according to Islam.


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Perhaps more importantly, SpringWorks sees potential for Ogsiveo as a potentiator for BCMA-targeted multiple myeloma therapies. The idea is that by inhibiting gamma secretase, Ogsiveo can prevent the cleavage of the BCMA receptors off tumor cell surfaces, and thereby increasing the BCMA target density for drugs.

To test this theory, company has entered clinical development partnerships to combine Ogsiveo with GSK’s antibody-drug conjugate Blenrep, with Johnson & Johnson’s T-cell engager Tecvayli and with Pfizer’s bispecific Elrexfio.

Aside from Ogsiveo, SpringWorks recently reported positive pivotal data for its mirdametinib for the rare disease plexiform neurofibroma. The company now plans to file an application with the FDA in the first half of 2024.