European Commission grants approval of Ogsiveo (nirogacestat) for treatment of desmoid tumors – Merck

Merck KGaA, announced 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,

The EC approval of Ogsiveo is based on results from the Phase III 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).

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%).

DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase III 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.

“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.”

“We would like to extend our gratitude to the patients, families, investigators, and advocacy organizations who helped make this EC approval possible,” said Dr. Danny Bar-Zohar, 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.”

“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 Prof. Bernd Kasper, 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.”