Selumetinib Earns Positive CHMP Opinion for Adult NF1-Associated PNs

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of selumetinib (Koselugo) for the treatment of symptomatic, inoperable plexiform neurofibromas (PNs) in adult patients with neurofibromatosis type 1 (NF1).1

The recommendation is supported by data from the phase 3 KOMET trial (NCT04924608), which showed that patients treated with selumetinib (n = 71) experienced an overall response rate (ORR) by week 16 of 20% (95% CI, 11.2%-30.9%) compared with 5% (95% CI, 1.5%-13.3%) for those given placebo (n = 74; P = .01).

Previously, selumetinib was approved in the European Union for the treatment of select pediatric patients with NF1-associated PNs.

“For adults with NF1, tumor growth doesn’t stop at childhood and can rapidly progress or develop into adulthood, impacting physical, emotional and social well-being,” Pierre Wolkenstein, MD, PhD, head of the Department of Dermatology at Henri Mondor Hospital, APHP, Paris East University (UPEC), and national coordinating investigator of the KOMET trial in Europe, stated in a news release. “The positive recommendation by the CHMP for [selumetinib] in adults underscores the urgent need for additional targeted treatments for this patient population. When approved, [selumetinib] could offer a treatment option for adult patients and continuity of care across age groups, supported by established clinical experience and practice among doctors managing this lifelong condition.”

In July 2025, the first treatment for adult patients with NF1-associated PNs was approved in the EU, with the European Commission granting conditional marketing authorization for mirdametinib (Ezmekly) for the treatment of symptomatic, inoperable plexiform neurofibromas (PNs) in adult and pediatric patients 2 years of age and older with NF1.2

What Did the KOMET Trial Investigate?

KOMET was a global, randomized, double-blind, placebo-controlled, multicenter, phase 3 trial that enrolled patients at least 18 years of age with NF1 and symptomatic, inoperable PNs who had at least 1 inoperable target lesion that was measurable per volumetric MRI.3 Patients also needed to have a chronic target PN pain score documented during the screening period, use of stable chronic PN pain medication at enrollment, and adequate organ and bone marrow function.

The trial included 145 adult patients from 13 countries across North America, South America, Europe, Asia, and Australia.

Patients were randomly assigned 1:1 to receive selumetinib or placebo, with treatment administered for 12 28-day cycles in each arm. After 12 cycles, patients on placebo began to receive selumetinib, and those in the experimental arm continued treatment with the MEK inhibitor for an additional 12 cycles. Patients who finished 24 cycles of treatment were allowed to continue to receive selumetinib during a long-term extension period.

ORR by cycle 16, as assessed by independent central review, served as the trial’s primary end point. Secondary end points comprised improved PN-related pain and health-related quality of life (HRQOL) at cycle 12.

“The CHMP positive opinion of [selumetinib] in adults with NF1[-associated] PN builds on more than a decade of global clinical and real-world experience, reflecting the unmatched body of evidence supporting the safety profile and efficacy of [selumetinib],” Marc Dunoyer, chief executive officer of Alexion, added in a news release.1 “As demonstrated by the results from KOMET, the largest and only placebo-controlled, double-blind global phase 3 trial in an adult population, we continue to advance the pioneering legacy of [selumetinib], which set the treatment standard in NF1-associated PN, to reach even more people worldwide.”

References

1. 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 September 22, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/koselugo-recommended-for-eu-approval.html#!
2. The European Commission has granted conditional approval of Ezmekly (mirdametinib) for the treatment of adult and pediatric patients with neurofibromatosis type 1–associated plexiform neurofibromas (NF1-PN). News release. SpringWorks Therapeutics. July 18, 2025. Accessed September 22, 2025. https://springworkstx.gcs-web.com/news-releases/news-release-details/european-commission-grants-conditional-approval-ezmeklyr
3. Efficacy and safety of selumetinib in adults with NF1 who have symptomatic, inoperable plexiform neurofibromas (KOMET). ClinicalTrials.gov. Updated Decemebr 9, 2024. Accessed September 22, 2025. https://clinicaltrials.gov/study/NCT04924608