SpringWorks Therapeutics Gets Positive CHMP Opinion for Nirogacestat in Desmoid Tumors Treatment

SpringWorks Therapeutics, Inc., a biopharmaceutical company focused on rare diseases and cancer treatments, has announced a significant development regarding their drug nirogacestat. The European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) has given a favorable opinion recommending that nirogacestat be approved for use in the treatment of desmoid tumors. Desmoid tumors are rare, aggressive growths in soft tissues that can be debilitating and, on rare occasions, life-threatening. Currently, there are no approved medications for treating desmoid tumors in Europe, making this recommendation a notable advancement.

Nirogacestat, an oral gamma secretase inhibitor, is intended for use as a monotherapy in adults whose desmoid tumors are progressing and require systemic treatment. If it receives approval, it will be the first such therapy available in the European Union for this condition. The European Commission is expected to make its final decision regarding this approval in the third quarter of 2025.

This positive recommendation from the CHMP is backed by data from the Phase 3 DeFi trial. Published in The New England Journal of Medicine, the trial demonstrated that nirogacestat significantly improved progression-free survival, reducing the risk of disease progression by 71% compared to placebo. It also showed considerable benefits in objective response rates and patient-reported outcomes, including reductions in pain, improvements in physical function, and overall quality of life. The trial highlighted nirogacestat's manageable safety profile, noting common adverse reactions such as diarrhea, ovarian toxicity, rash, nausea, and fatigue among others.

Desmoid tumors, although non-metastatic, have high recurrence rates post-surgical removal, prompting experts to recommend systemic therapies as first-line treatments. Nirogacestat has already been approved in the United States for treating adults with progressing desmoid tumors requiring systemic intervention. The DeFi trial was an extensive global study, incorporating a double-blind, placebo-controlled design to ensure robust assessment of nirogacestat's efficacy and safety.

This trial involved 142 patients, divided equally to receive either nirogacestat or a placebo. The primary endpoint was progression-free survival, assessed through blinded independent central review. Secondary measures included safety evaluations, objective response rates, and patient-reported outcomes. An open-label extension phase followed the initial trial phase for further evaluation.

SpringWorks Therapeutics, headquartered in Stamford, Connecticut, continues to focus on developing treatments for severe rare diseases and cancer. This latest advancement with nirogacestat reflects their commitment to expanding treatment options for patients globally, especially in regions where such therapies are not yet available.

The significance of this potential approval is underscored by the fact that desmoid tumors are most prevalent in individuals between 20 and 44 years old, with a higher occurrence among females. Within the European Union, approximately 1,300 to 2,300 new cases are diagnosed annually. The anticipation surrounding the European Commission's decision reflects the urgent need for effective treatments for this challenging condition.

SpringWorks Therapeutics remains at the forefront of developing targeted therapies, having already commercialized FDA-approved treatments for desmoid tumors and neurofibromatosis type 1 associated plexiform neurofibromas. Their continued efforts aim to address various solid and hematological tumors, offering hope and improved quality of life for patients living with severe rare diseases and cancers.