FDA Approves Ogsiveo to Treat Desmoid Tumors

The FDA has approved nirogacestat (Ogsiveo) for adults with progressing desmoid tumors requiring systemic treatment.^1,2 The action makes Ogsiveo the first FDA-approved treatment for desmoid tumors. The approval was supported by results from the Phase 3 DeFi trial (NCT03785964), which showed that Ogsiveo reduced the risk of disease progression or mortality by 71% compared with placebo.

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“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 DeFi investigator Mrinal M. Gounder, MD, sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, New York, in a press release.³ “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.”

Desmoid tumors, or aggressive fibromatosis, are most commonly diagnosed in patients between 20 and 44 years of age, with a prevalence up to three times higher in women. Historically, desmoid tumors were treated with surgical resection, although a high recurrence rate after surgery elevates the need for effective treatments.

Desmoid tumors are noncancerous growths that develop in connective tissue, most commonly found in the abdomen, arms, and legs. Some desmoid tumors grow slowly without a need for immediate treatment, whereas other types of the tumor rapidly develop and require surgery, radiation therapy, chemotherapy, or other treatments. Although these tumors are not considered cancers because they don't metastasize to other areas of the body, desmoid tumors can grow aggressively into nearby structures and organs.⁴

The global, randomized, double-blind, placebo-controlled DeFi trial analyzed the efficacy, safety, and tolerability of Ogsiveo in patients with progressing desmoid tumors. The trial randomly assigned 142 patients to receive 150 mg of Ogsiveo or placebo twice daily with the primary endpoint of progression-free survival (PFS). Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume, and changes in patient-reported outcomes.

In the trial, median PFS in the Ogsiveo cohort was not yet reached compared with 15.1 months in the placebo cohort. The trial achieved all key secondary endpoints, with statistically significant improvements in ORR and patient-reported outcomes vs. placebo.

Ogsiveo was generally well tolerated with a manageable safety profile. Most women with childbearing potential had adverse events that were found to be consistent with ovarian dysfunction and were generally consistent with previously reported data.

Ogsiveo was previously granted Orphan Drug Designation for desmoid tumors and from the European Commission for soft tissue sarcoma. The FDA also granted the drug Fast Track and Breakthrough Therapy Designations for adults with progressive, unresectable, recurrent, or refractory desmoid tumors or deep fibromatosis.

References

1. FDA approves nirogacestat for desmoid tumors. FDA. November 27, 2023. Accessed November 28, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nirogacestat-desmoid-tumors

2. Ogsiveo (nirogacestat). Prescribing information. SpringWorks Therapeutics, Inc. Updated November 2023. Accessed November 28, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217677s000lbl.pdf

3. SpringWorks Therapeutics announces FDA approval of Ogsiveo (nirogacestat) as the first and only treatment for adults with desmoid tumors. News release. SpringWorks Therapeutics, Inc. November 27, 2023. Accessed November 28, 2023. https://ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-fda-approval-ogsiveotm

4. Desmoid tumors. Mayo Clinic. Webpage. Updated January 22, 2022. Accessed November 28, 2023. https://www.mayoclinic.org/diseases-conditions/desmoid-tumors/symptoms-causes/syc-20355083#:~:text=Desmoid%20tumors%20are%20noncancerous%20growths,don't%20require%20immediate%20treatment.