European Commission Grants Approval of Ogsiveo

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

Merck KGaA, Darmstadt, Germany, a leading science and technology company, 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. The approval was issued to SpringWorks Therapeutics Inc., a healthcare company of Merck KGaA, Darmstadt, Germany.

“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 diarrhea (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.

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-approved medicine for adults with desmoid tumors and the first and only 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.