European Commission Grants Approval of OGSIVEO® (nirogacestat) for the Treatment of Adults with Desmoid Tumors

OGSIVEO is the first and only therapy to receive marketing authorization in the EU for the treatment of desmoid tumors

STAMFORD, Conn., Aug. 18, 2025 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc., a healthcare company of Merck, announced today that the European Commission (EC) granted marketing authorization for OGSIVEO^® (nirogacestat), an oral gamma secretase inhibitor, as monotherapy for the treatment of adults with progressing desmoid tumors who require systemic treatment. OGSIVEO is the first and only therapy approved in the European Union (EU) to treat desmoid tumors.

“Desmoid tumors can have a profound impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence. Until now, there have been no approved medicines in Europe,” said Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial. “OGSIVEO is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms, including a significant reduction in pain which is the most debilitating symptom reported by patients.”

“This approval is a long-awaited advance for desmoid tumor patients, their families and physicians in Europe,” said Lynne Hernandez, Executive Director of the Desmoid Tumor Research Foundation. “It is our hope that patients will benefit from greater awareness of desmoid tumors, faster diagnoses, and better outcomes now that there is an approved treatment.”

Desmoid tumors are rare, locally aggressive tumors that form in the connective tissues of the body.^1,2 Approximately 1,300 to 2,300 new cases of desmoid tumors are diagnosed annually in the EU.^3,4,5 These tumors can cause severe pain, limited function, loss of mobility, disfigurement and fatigue.^1,6-10 They are challenging to manage because of their unpredictable nature and high rate of recurrence, which can significantly impact an individual’s quality of life.^2,7,8,11,12 Desmoid tumor experts and treatment guidelines now recommend medical therapy as first-line intervention instead of surgery for most tumor locations requiring treatment.^13,14

“We would like to extend our gratitude to the patients, families, investigators, and advocacy organizations who helped make this EC approval possible,” said Danny Bar-Zohar, MD, CEO of Healthcare and Executive Board Member at Merck KGaA, Darmstadt, Germany. “OGSIVEO is already established as the standard of care systemic therapy for desmoid tumors in the U.S., and our goal is to bring the same treatment benefits to patients in Europe. Following last month’s EC approval of our therapy for patients with NF1-PN, we are in the unique position of launching two innovative treatments -- underscoring our commitment to the rare tumor patient community.”

The EC approval of OGSIVEO is based on results from the Phase 3 DeFi trial, which enrolled 142 adult patients with progressing desmoid tumors and met the primary endpoint of improving progression-free survival (PFS). OGSIVEO demonstrated 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). OGSIVEO also demonstrated a significant improvement in objective response rate (ORR). The confirmed 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. Additionally, OGSIVEO demonstrated early and sustained improvement 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).¹³

OGSIVEO exhibited a manageable safety and tolerability profile. The most common adverse reactions reported in 88 patients receiving OGSIVEO across all studies (69 patients from DeFi and 19 patients from early phase studies) were diarrhoea (85%), rash (65%), ovarian toxicity in women of childbearing potential (60%) nausea (59%), fatigue (50%), hypophosphataemia (50%), headache (40%) and stomatitis (40%).¹³

About the DeFi Trial

DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate, duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes. DeFi also included an open-label extension phase.

About Desmoid Tumors

Desmoid tumors are rare, locally aggressive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.^1,2

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.^3,11 It is estimated that there are 1,300-2,300 new desmoid tumor cases diagnosed per year in the European Union. ^3,4,5

Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.^11,12 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.^14,15

About OGSIVEO^® (nirogacestat)

OGSIVEO^® (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States and European Union as monotherapy for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

The FDA and the EMA have granted Orphan Drug designation for OGSIVEO for the treatment of desmoid tumors.

For the full list of side effects and restrictions with OGSIVEO, see the full Summary of Product Characteristics.

IMPORTANT SAFETY INFORMATION

Diarrhoea
Diarrhoea was reported in patients receiving nirogacestat. Patients who experience diarrhoea during treatment with nirogacestat should be monitored and managed using anti‑diarrhoeal medicinal products. For Grade 3 diarrhoea that persists for ≥ 3 days despite maximal medical therapy, nirogacestat should be withheld until diarrhoea is resolved to Grade ≤ 1 or baseline, then it should be restarted at 100 mg twice daily.

Skin and subcutaneous tissue disorders
Dermatologic reactions, including maculopapular rash, folliculitis, and hidradenitis, were reported in patients receiving nirogacestat. Patients should be monitored for dermatologic reactions throughout the course of treatment and managed as clinically indicated. For Grade 3 dermatologic reactions, nirogacestat should be withheld until resolved to Grade ≤ 1 or baseline, then it should be restarted at a dose of 100 mg twice daily.

Ovarian toxicity
Ovarian toxicity was reported in female patients of childbearing potential receiving nirogacestat. Ovarian toxicity, identified based on abnormal reproductive hormone levels or peri‑menopausal symptoms, was reported in 75% of women of childbearing potential receiving nirogacestat in the DeFi study. Ovarian toxicity has been reported to resolve in 79% of women of childbearing potential during treatment. Follow up information is available for all but two out of 27 patients; after stopping treatment, ovarian toxicity was reported to resolve in all women of childbearing potential for whom data are available. Effects of nirogacestat on human fertility are unknown. Based on findings from animal studies, female fertility may be impaired. Women of childbearing potential should be advised about the risk of ovarian toxicity before initiating treatment with nirogacestat. Patients should be monitored for changes in menstrual cycle regularity or the development of symptoms of oestrogen deficiency, including hot flashes, night sweats, and vaginal dryness.

Electrolyte abnormalities
Electrolyte abnormalities, including hypophosphataemia and hypokalaemia, were reported in patients receiving nirogacestat. Phosphate and potassium levels should be monitored regularly and supplemented as necessary. For Grade 3 hypophosphataemia persisting for ≥ 7 days despite maximal replacement therapy, nirogacestat should be withheld until resolved to Grade ≤ 1 or baseline, then it should be restarted at a dose of 100 mg twice daily. For Grade 3 hypokalaemia of any duration, despite maximal replacement therapy, nirogacestat should be withheld until resolved to Grade ≤ 1 or baseline, then it should be restarted at a dose of 100 mg twice daily.

Hepatic abnormalities
ALT or AST elevations were reported in patients who received nirogacestat. Liver function tests should be monitored regularly. For ALT or AST ≥ 3 to 5 x ULN, nirogacestat should be withheld until ALT, AST, or both are resolved to < 3 x ULN or baseline, then it should be restarted at a dose of 100 mg twice daily. For ALT or AST > 5 x ULN, nirogacestat should be permanently discontinued (see section 4.2).

Non‑melanoma skin cancers
Non‑melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) were reported in patients receiving nirogacestat. Skin examinations should be performed prior to initiation of nirogacestat and routinely during treatment with nirogacestat. Cases should be managed according to clinical practices and patients may continue with nirogacestat treatment without dose adjustment.

Embryo‑foetal toxicity – Contraception in males and females
Nirogacestat may cause foetal harm when administered to a pregnant woman. Patients should be advised of the potential risk to a foetus. Women of childbearing potential must have a negative pregnancy test prior to initiating nirogacestat treatment. Pregnancy testing during treatment with nirogacestat should be considered for women of childbearing potential experiencing amenorrhoea. Women of childbearing potential receiving nirogacestat must use highly effective contraceptive methods during treatment with nirogacestat and for 1 week after the last dose of nirogacestat. Women of childbearing potential should be advised to inform their healthcare provider immediately of a known or suspected pregnancy, and they must stop taking nirogacestat if they become pregnant. Male patients with female partners of childbearing potential should be advised to use highly effective contraceptive methods during treatment with nirogacestat and for 1 week after the last dose of nirogacestat.

About SpringWorks Therapeutics

SpringWorks Therapeutics, a healthcare company of Merck, is a commercial-stage biopharmaceutical company dedicated to improving the lives of patients with rare tumors. We developed and are commercializing the first and only FDA and EC approved medicine for adults with desmoid tumors and the first and only FDA and EC approved medicine for both adults and children with neurofibromatosis type 1 associated plexiform neurofibromas (NF1-PN). We are also advancing a portfolio of novel targeted therapy product candidates for patients with additional rare tumors and hematological cancers.

For more information, visit www.springworkstx.com and follow @SpringWorksTx on X, LinkedIn, Facebook, Instagram and YouTube.

About Merck

Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 62,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2024, Merck generated sales of € 21.2 billion in 65 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.

All Merck press releases are distributed by e-mail at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

Contacts:

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References

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