The regulatory decision was supported by data from the phase 3 KOMET trial (NCT04924608). Findings from KOMET presented during the 2025 ASCO Annual Meeting and subsequently published in The Lancet demonstrated that patients who received selumetinib (n = 71) experienced an overall response rate (ORR) of 20% (95% CI, 11.2%-30.9%) compared with 5% (95% CI, 1.5%-13.3%) among patients who received placebo (n = 74; P = .0112).2,3 This finding met the primary end point of the study.
“The approval of [selumetinib] for adults with NF1 PN in Europe offers patients and physicians a meaningful approach to close treatment gaps beyond childhood,” Pierre Wolkenstein, MD, PhD,the head of the Department of Dermatology at Henri Mondor Hospital, APHP, Paris East University in France, and the national coordinating investigator of the KOMET trial in Europe, stated in a news release.1 “As demonstrated in the [phase 3] KOMET trial, the most robust late-stage clinical trial conducted in this patient group to-date, adults administered [selumetinib] saw significant tumor volume reduction with a safety profile consistent with its established use in pediatric patients, validating the clinical benefits of [selumetinib] for newly diagnosed adults and those transitioning to adult care.”
This regulatory decision follows a positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use in September 2025, which recommended the approval of selumetinib for the treatment of symptomatic, inoperable PNs in adult patients with NF1.4
How was KOMET Designed?
KOMET was a multicenter, international, double-blind trial that enrolled adult patients with NF1 and symptomatic, inoperable PNs.2,3 Patients were required to have a baseline PAINS-pNF score of at least 1, be MEK inhibitor–naive, be receiving stable chronic pain medication at baseline, and have an ability to swallow whole capsules.2
Following a pain diary run-in, patients were randomly assigned to receive oral selumetinib at 25 mg/m2 twice daily or placebo. Following the 12-cycle randomized period, patients in the placebo arm were permitted to crossover to the selumetinib arm for the 12-cycle open-label period if disease progression on MRI assessment occurred.
The primary end point was ORR at the end of cycle 16 per independent review committee by REiNS criteria. Key secondary end points included change in chronic PN pain intensity and change in health-related quality of life with selumetinib vs placebo at cycle 12. Safety and tolerability outcomes were also assessed, including adverse effects (AEs), vital signs, clinical laboratory assessments, and physical examinations.
What was the safety profile of selumetinib?
No new safety concerns were identified with selumetinib for the treatment of patients with NF1-associated PNs. The most common any-grade treatment-emergent AEs (TEAEs) that occurred in at least 10% of patients during the randomization period in the investigational arm included dermatitis acneiform (59%), increased blood creatine phosphokinase levels (42%), and diarrhea (28%). The most common any-grade TEAEs during the same period in the control arm included diarrhea (12%), nausea (11%), alopecia (10%), and fatigue (10%).
“The European Commission approval extends the life-changing potential of [selumetinib] to adults with NF1 PN in the region, including continuity of care into adulthood,” Marc Dunoyer, the chief executive officer of Alexion added in the news release.1 “This milestone, along with our pioneering leadership in NF1 PN treatment landscape, embodies Alexion’s unwavering commitment to addressing the unmet needs in the rare disease community. We look forward to bringing [selumetinib] to those adults in need across Europe as soon as possible.”
References
- Koselugo approved in the EU for plexiform neurofibromas in adults with neurofibromatosis type 1. News release. AstraZeneca. October 28, 2025. Accessed October 28, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/koselugo-approved-in-the-eu-for-plexiform-neurofibromas-in-adults-with-neurofibromatosis-type-1.html
- Chen AP, O’Sullivan Coyne GH, Wolters P, et al. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): primary analysis of KOMET (NCT04924608), a phase 3, international, randomized, placebo-controlled study. J Clin Oncol. 2025;43(suppl 16):3014. doi:10.1200/JCO.2025.43.16_suppl.3014
- Chen AP, Coyne GO, Wolters PL, et al. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study. Lancet. 2025;405(10496):2217-2230. doi:10.1016/S0140-6736(25)00986-9
- Koselugo recommended for approval in the EU by CHMP for plexiform neurofibromas in adults with neurofibromatosis type 1. News release. AstraZeneca. September 22, 2025. Accessed October 28, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/koselugo-recommended-for-eu-approval.html
