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Pictured: Signage outside the FDA's headquarters, DC/iStock, JHVEPhoto The FDA on Monday approved SpringWorks Therapeutics’ oral drug nirogacestat for the treatment of non-cancerous progressing desmoid tumors, which can lead to severe pain and disability. The Stamford, Conn.-based biotech will market nirogacestat under the brand name Ogsiveo. With Monday’s regulatory win, Ogsiveo now becomes the “first FDA-approved therapy for patients with desmoid tumors,” SpringWorks CEO Saqib Islam said in a statement, adding that Ogsiveo’s broad label— which specifically references the treatment’s pain improvements—could potentially position the drug as “the new standard of care” in this indication. Islam also called Monday’s approval a “watershed moment” for the desmoid tumor community, which for years had been waiting for an effective treatment that shrinks tumors and eases pain. With around 1,000 to 1,650 new cases per year, desmoid tumors are rare soft-tissue lesions that, while non-cancerous, are typically locally aggressive and which may invade surrounding tissues and organs. In turn, patients with desmoid tumors suffer from often-debilitating pain, impaired mobility and overall lower quality of life. According to the FDA’s announcement on Ogsiveo’s approval, the standard treatment approach to desmoid tumors is to remove them through surgery, though this carries a high risk of recurrence and complications. Ogsiveo is an oral, selective and small-molecule inhibitor of the gamma secretase protein, which cleaves the transmembrane complex Notch, a crucial component in signaling cascades underlying the growth of desmoid tumors. This mechanism of action, along with promising pre-clinical and clinical data, have won Ogsiveo the FDA’s Fast Track, Breakthrough Therapy and Orphan Drug designations. The regulator’s approval was based on data from the Phase III DeFi study, which demonstrated a statistically significant improvement in progression-free survival in patients treated with Ogsiveo. As compared with placebo, patients who received SpringWorks’ oral drug saw a 71% drop in the risk of disease progression or death. Patient-reported outcomes, including pain, physical function, disease-specific symptoms and overall health-related quality of life, were all likewise significantly better in Ogsiveo-treated patients than in placebo comparators. As for safety, DeFi found Ogsiveo to have a manageable tolerability profile. Common adverse events included diarrhea, rashes, fatigue, headaches and dyspnea. Results from DeFi were also published in March 2023 in The New England Journal of Medicine. Under its label, Ogsiveo is indicated for adult patients who require systemic treatment. The drug does not carry a boxed warning but comes with precautions against severe diarrhea, ovarian toxicity, hepatotoxicity, embryo-fetal toxicities and electrolyte abnormalities. Patients being treated with Ogsiveo can also develop new non-melanoma skin cancers. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.