European Commission Grants Approval of OGSIVEO庐 (nirogacestat) for the Treatment of Adults with Desmoid Tumors
SpringWorks Therapeutics (SWTX) has achieved a significant milestone as the European Commission granted marketing authorization for OGSIVEO庐 (nirogacestat), making it the first and only approved therapy in the EU for treating adults with progressing desmoid tumors requiring systemic treatment.
The approval is based on the Phase 3 DeFi trial results, which demonstrated remarkable efficacy including a 71% reduction in disease progression risk and a 41% objective response rate compared to 8% with placebo. The therapy showed significant improvements in patient-reported outcomes, including pain reduction and quality of life measures.
OGSIVEO addresses an important unmet need for approximately 1,300 to 2,300 new cases of desmoid tumors diagnosed annually in the EU. The treatment has already established itself as the standard of care systemic therapy in the U.S.
SpringWorks Therapeutics (SWTX) ha raggiunto un traguardo importante: la Commissione Europea ha autorizzato la commercializzazione di OGSIVEO庐 (nirogacestat), rendendolo la prima e unica terapia approvata nell'UE per il trattamento di adulti con tumori desmoidi in progressione che necessitano di terapia sistemica.
L'approvazione si basa sui risultati dello studio di Fase 3 DeFi, che hanno mostrato una notevole efficacia, con una riduzione del 71% del rischio di progressione della malattia e un tasso di risposta obiettiva del 41% rispetto all'8% con placebo. La terapia ha inoltre determinato miglioramenti significativi negli esiti riferiti dai pazienti, inclusa la riduzione del dolore e la qualit脿 della vita.
OGSIVEO risponde a un importante bisogno non soddisfatto per circa 1.300-2.300 nuovi casi di tumori desmoidi diagnosticati ogni anno nell'UE. Il trattamento 猫 gi脿 diventato lo standard di cura sistemica negli Stati Uniti.
SpringWorks Therapeutics (SWTX) ha logrado un hito importante: la Comisi贸n Europea ha concedido la autorizaci贸n de comercializaci贸n de OGSIVEO庐 (nirogacestat), convirti茅ndolo en la primera y 煤nica terapia aprobada en la UE para el tratamiento de adultos con tumores desmoides en progresi贸n que requieren tratamiento sist茅mico.
La aprobaci贸n se basa en los resultados del ensayo de Fase 3 DeFi, que demostraron una eficacia notable, incluyendo una reducci贸n del 71% del riesgo de progresi贸n de la enfermedad y una tasa de respuesta objetiva del 41% frente al 8% con placebo. La terapia mostr贸 adem谩s mejoras significativas en los resultados informados por los pacientes, incluyendo la reducci贸n del dolor y la calidad de vida.
OGSIVEO cubre una necesidad importante no satisfecha para aproximadamente 1.300 a 2.300 nuevos casos de tumores desmoides diagnosticados anualmente en la UE. El tratamiento ya se ha establecido como el est谩ndar de atenci贸n sist茅mica en EE. UU.
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OGSIVEO電� 毵る厔 EU鞐愳劀 歆勲嫧霅橂姅 鞎� 1,300词2,300瓯�鞚� 雿办姢氇澊霌� 膦呾枒鞚措澕電� 欷戩殧頃� 氙胳订臁� 靾橃殧毳� 頃搓舶頃╇媹雼�. 鞚� 旃橂氩曥潃 鞚措 氙戈淡鞐愳劀 鞝勳嫚 旃橂鞚� 響滌 旃橂搿� 鞛愲Μ鞛§晿鞀惦媹雼�.
SpringWorks Therapeutics (SWTX) a franchi une 茅tape importante : la Commission europ茅enne a accord茅 l'autorisation de mise sur le march茅 de OGSIVEO庐 (nirogacestat), faisant de ce traitement le premier et le seul approuv茅 dans l'UE pour les adultes atteints de tumeurs desmo茂des en progression n茅cessitant un traitement syst茅mique.
Cette autorisation repose sur les r茅sultats de l'essai de phase 3 DeFi, qui ont d茅montr茅 une efficacit茅 remarquable, avec une r茅duction de 71% du risque de progression de la maladie et un taux de r茅ponse objective de 41% contre 8% avec le placebo. Le traitement a 茅galement entra卯n茅 des am茅liorations significatives des r茅sultats rapport茅s par les patients, notamment une diminution de la douleur et une meilleure qualit茅 de vie.
OGSIVEO r茅pond 脿 un besoin important non couvert pour environ 1 300 脿 2 300 nouveaux cas de tumeurs desmo茂des diagnostiqu茅s chaque ann茅e dans l'UE. Le traitement s'est d茅j脿 impos茅 comme la th茅rapie syst茅mique de r茅f茅rence aux 脡tats-Unis.
SpringWorks Therapeutics (SWTX) hat einen wichtigen Meilenstein erreicht: Die Europ盲ische Kommission hat die Marktzulassung f眉r OGSIVEO庐 (nirogacestat) erteilt und damit die erste und einzige zugelassene Therapie in der EU f眉r erwachsene Patientinnen und Patienten mit progredienten desmoidalen Tumoren, die eine systemische Behandlung ben枚tigen, geschaffen.
Die Zulassung basiert auf den Ergebnissen der Phase-3-Studie DeFi, die eine bemerkenswerte Wirksamkeit zeigte, einschlie脽lich einer 71%igen Reduktion des Risikos f眉r Krankheitsprogression und einer objektiven Ansprechrate von 41% gegen眉ber 8% unter Placebo. Die Therapie f眉hrte zudem zu signifikanten Verbesserungen bei patientenberichteten Ergebnissen, etwa Schmerzreduktion und Lebensqualit盲t.
OGSIVEO deckt einen wichtigen ungedeckten Bedarf f眉r etwa 1.300 bis 2.300 neue F盲lle von desmoiden Tumoren ab, die j盲hrlich in der EU diagnostiziert werden. Die Behandlung hat sich in den USA bereits als systemische Standardtherapie etabliert.
- None.
- Common adverse reactions including diarrhea (85%), rash (65%), and ovarian toxicity (60%)
- Median time to first response of 5.6 months indicates delayed treatment effect
Insights
SpringWorks secures groundbreaking EU approval for OGSIVEO, becoming the first approved therapy for desmoid tumors in Europe.
The European Commission's approval of OGSIVEO庐 (nirogacestat) represents a significant regulatory milestone for SpringWorks Therapeutics. As the first and only therapy approved in the EU for desmoid tumors, this decision grants SpringWorks a complete market advantage in addressing an underserved patient population. The approval's foundation on the Phase 3 DeFi trial data demonstrates robust clinical evidence with OGSIVEO showing a 71% reduction in disease progression risk compared to placebo (HR = 0.29) and a confirmed objective response rate of 41% versus 8% for placebo.
Particularly compelling are the complete response rates of 7% (versus 0% for placebo) and the significant improvements in patient-reported outcomes including pain reduction and quality of life metrics. These patient-centric benefits typically enhance adoption rates and support reimbursement discussions with European health authorities. The manageable safety profile with predictable side effects like diarrhea (85%) and rash (65%) aligns with expectations for this drug class.
With an estimated 1,300 to 2,300 new cases annually in the EU, OGSIVEO is positioned to become the standard of care in Europe as it already is in the US. The timing is strategic, following closely behind another EC approval for SpringWorks' therapy for NF1-PN patients, indicating a focused regulatory execution strategy and portfolio expansion within rare diseases. This approval will likely accelerate diagnosis rates and establish treatment protocols throughout European healthcare systems, creating a sustainable market position.
OGSIVEO's EU approval establishes SpringWorks as the dominant player in desmoid tumor treatment, unlocking significant European market potential.
This approval represents an exceptional market opportunity for SpringWorks in the European rare disease landscape. Desmoid tumors, while rare, represent a completely untapped market with no previous approved therapies in Europe. The company is positioned to convert approximately 1,300-2,300 new patients annually into a stable revenue stream with minimal competition.
The clinical profile presents compelling value for payers and providers - particularly the significant improvement in patient-reported outcomes related to pain, functioning, and quality of life. These metrics are increasingly critical in European reimbursement decisions, especially for high-priced rare disease treatments. The 41% objective response rate provides quantifiable efficacy that will support pricing discussions.
Market penetration should benefit from the evolving treatment paradigm, as noted in the release: "Desmoid tumor experts and treatment guidelines now recommend medical therapy as first-line intervention instead of surgery." This shift creates an immediate addressable market beyond just newly diagnosed patients, potentially including previously diagnosed patients initially managed with watchful waiting or surgical approaches.
The sequential approval strategy, following their recent EU approval for NF1-PN treatment, demonstrates operational efficiency in navigating European regulatory pathways. This creates commercial synergies as SpringWorks can leverage a single rare disease-focused European commercial infrastructure to support both products. With endorsement from the Desmoid Tumor Research Foundation and key opinion leaders like Prof. Kasper, SpringWorks has established the advocacy relationships necessary for successful market access in fragmented European healthcare systems.
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 KGaA, Darmstadt, Germany, announced today that the European Commission (EC) granted marketing authorization for OGSIVEO庐 (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.
鈥淒esmoid tumors can have a profound impact on people鈥檚 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,鈥� said Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial. 鈥淥GSIVEO 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.鈥�
鈥淭his approval is a long-awaited advance for desmoid tumor patients, their families and physicians in Europe,鈥� said Lynne Hernandez, Executive Director of the Desmoid Tumor Research Foundation. 鈥淚t 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.鈥�
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鈥檚 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
鈥淲e would like to extend our gratitude to the patients, families, investigators, and advocacy organizations who helped make this EC approval possible,鈥� said Danny Bar-Zohar, MD, CEO of Healthcare and Executive Board Member at Merck KGaA, Darmstadt, Germany. 鈥淥GSIVEO 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鈥檚 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.鈥�
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
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 diarrhea (
About the DeFi Trial
DeFi () 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 鈮�
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
About OGSIVEO庐 (nirogacestat)
OGSIVEO庐 (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.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- Diarrhea: Diarrhea occurred in
84% of patients treated with OGSIVEO. Grade 3 events occurred in16% of patients. Monitor patients and manage using antidiarrheal medications. Modify dose as recommended. - Ovarian Toxicity: Female reproductive function and fertility may be impaired in patients treated with OGSIVEO. Impact on fertility may depend on factors like duration of therapy and state of gonadal function at time of treatment. Long-term effects on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness.
- Hepatotoxicity: ALT or AST elevations occurred in
30% and33% of patients, respectively. Grade 3 ALT or AST elevations (>5 脳 ULN) occurred in6% and2.9% of patients. Monitor liver function tests regularly and modify dose as recommended. - Non-Melanoma Skin Cancers: New cutaneous squamous cell carcinoma and basal cell carcinoma occurred in
2.9% and1.4% of patients, respectively. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment. - Electrolyte Abnormalities: Decreased phosphate (
65% ) and potassium (22% ) occurred in OGSIVEO-treated patients. Phosphate <2 mg/dL occurred in20% of patients. Grade 3 decreased potassium occurred in1.4% of patients. Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended. - Embryo-Fetal Toxicity: Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at maternal exposures below human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose.
ADVERSE REACTIONS
- The most common (鈮�
15% ) adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. - Serious adverse reactions occurring in 鈮�
2% of patients were ovarian toxicity (4% ). - The most common laboratory abnormalities (鈮�
15% ) were decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
DRUG INTERACTIONS
- CYP3A Inhibitors and Inducers: Avoid concomitant use with strong or moderate CYP3A inhibitors (including grapefruit products, Seville oranges, and starfruit) and strong or moderate CYP3A inducers.
- Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors and H2 blockers. If concomitant use cannot be avoided, OGSIVEO can be staggered with antacids (e.g., administer OGSIVEO 2 hours before or 2 hours after antacid use).
- Consult the full Prescribing Information prior to and during treatment for important drug interactions.
To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or .
Please see full for OGSIVEO for more information.
About SpringWorks Therapeutics
SpringWorks Therapeutics, a healthcare company of Merck KGaA, Darmstadt,听Germany, 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聽聽and follow聽聽on X,听,听,听听补苍诲听.
About Merck KGaA, Darmstadt,听Germany
Merck KGaA, Darmstadt,听Germany, 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鈥檚 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 鈥� the company is everywhere. In 2024, Merck KGaA, Darmstadt,听Germany, generated sales of
The company holds the global rights to the name and trademark 鈥淢erck鈥� internationally. The only exceptions are聽the United States听补苍诲听Canada, where the business sectors of Merck KGaA, Darmstadt,听Germany, operate as聽MilliporeSigma聽in life science,听EMD Serono聽in healthcare and聽EMD Electronics聽in electronics. Since its founding in 1668, scientific exploration and responsible entrepreneurship have been key to the company鈥檚 technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.
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References
- Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: News and Perspectives. Pathologica. 2021;113(2):70-84. doi:10.32074/1591-951X-213.
- Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, management and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274. doi:10.1097/CCO.0000000000000374.
- van Broekhoven DLM, Gr眉nhagen DJ, den Bakker MA, van Dalen T, Verhoef C. Time trends in the incidence and treatment of extra-abdominal and abdominal aggressive fibromatosis: a population-based study. Ann Surg Oncol. 2015;22(9):2817-2823. doi:10.1245/s10434-015-4632-y.
- Desmoid Tumor Working Group. The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96-107. doi:10.1016/j.ejca.2019.11.013.
- Eurostat. Population structure and ageing. European Commission. . Accessed June 12, 2025.
- Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, management and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274. doi:10.1097/CCO.0000000000000374.
- Constantinidou A, Scurr M, Judson I, Litchman C. Clinical presentation of desmoid tumors. In: Litchman C, ed. Desmoid Tumors. Springer; 2012:chap 2. . Accessed June 12, 2025.
- Bektas, M, et al. Desmoid tumors: a comprehensive review. Adv Therapeutics. 2023. doi.org/10.1007/s12325-023-02592-0.
- Husson O, Younger E, Dunlop A, et al. Desmoid fibromatosis through the patients鈥� eyes: time to change the focus and organisation of care? Support Care Cancer. 2019;27(3):965-980. doi:10.1007/s00520-018-4386-8.
- Gounder MM, Maddux L, Paty J, Atkinson TM. Prospective development of a patient-reported outcomes instrument for desmoid tumors or aggressive fibromatosis. Cancer. 2020;126(3):531-539. doi:10.1002/cncr.32555.
- Skubitz KM. Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964. doi:10.1016/j.mayocp.2017.02.012.
- Easter DW, Halasz NA. Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg. 1989;210(6):765-769. doi:10.1097/00000658-198912000-00012.
- OGSIVEO. EMA. Summary of product characteristics (SmPC). SpringWorks Therapeutics, Inc.
- Desmoid Tumor Working Group. The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96-107. doi:10.1016/j.ejca.2019.11.013.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines庐) for Soft Tissue Sarcoma V.2.2023. 漏 National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 12, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
FAQ
What is the significance of OGSIVEO's EU approval for SpringWorks Therapeutics (SWTX)?
How effective is OGSIVEO in treating desmoid tumors based on clinical trials?
What are the main side effects of OGSIVEO reported in clinical trials?
How many patients could potentially benefit from OGSIVEO in the European Union?
What improvements in patient outcomes were observed with OGSIVEO treatment?
