FDA approves of Ogsiveo (nirogacestat) as the first and only treatment for adults with desmoid tumors.- SpringWorks Therapeutics.

The FDA previously granted breakthrough therapy, fast track and orphan drug designations to nirogacestat for the treatment of 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,” said Saqib Islam, Chief Executive Officer of SpringWorks. "We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe Ogsiveo 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 Ogsiveo available in the U.S.”

Desmoid tumors are locally aggressive and invasive soft-tissue tumors that can lead to substantial morbidity. In addition, when vital structures are impacted, desmoid tumors can be life-threatening. Although they do not metastasize, desmoid tumors are often refractory to existing off-label systemic therapies and associated with recurrence rates of up to 77% following surgical resection. Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.

“Desmoid tumors can have a significant impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence. Ogsiveo is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” said Mrinal M. Gounder, M.D., sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center (MSK) in New York City and an investigator in the Phase III DeFi trial. “As a treating physician, it was encouraging to see in the DeFi trial that Ogsiveo achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile. This approval represents an important therapeutic advance for patients.”

The FDA approval of Ogsiveo is based on the results from the Phase III DeFi trial, which were published in the March 9, 2023 edition of the New England Journal of Medicine. (previously cited). Ogsiveo met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). Median PFS was not reached in the Ogsiveo arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on RECIST v1.1 was 41% with Ogsiveo versus 8% with placebo (p<0.001); the complete response rate was 7% in the ogsiveo arm and 0% in the placebo arm. the median time to first response was 5.6 months with ogsiveo and 11.1 months with placebo. pfs and orr improvements were in favor of ogsiveo regardless of baseline characteristics including sex, tumor location, tumor focality, treatment status, previous treatments, mutational status, and history of familial adenomatous polyposis. ogsiveo also demonstrated early and sustained improvements in patient-reported outcomes (pros), including pain (p><0.001), desmoid tumor-specific symptoms (p><0.001), physical role functioning (p><0.001), and overall health-related quality of life (p 0.01).

Ogsiveo exhibited a manageable safety and tolerability profile. The most common adverse events ( greater than 15%) reported in patients receiving Ogsiveo were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Warnings & Precautions relate to diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity.

As part of its commitment, the Company is introducing SpringWorks CareConnections, a comprehensive patient support program that offers personalized services to eligible Ogsiveo patients, including insurance coverage information and access support, financial assistance and personalized educational and emotional support. Physicians and patients can contact 1-844-CARES-55 (1-844-227-3755) or visit www.springworkstxcares.com for more information.

Ogsiveo will be available to order through a specialty pharmacy and specialty distributor network in the United States within five to ten business days. SpringWorks expects to file a Marketing Authorisation Application for Ogsiveo in desmoid tumors with the European Medicines Agency in the first half of 2024.