Written By: Pharmacally Medical News Desk
Koselugo (Selumetinib) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). This marks a significant expansion of its prior approval for pediatric patients, providing continuous treatment options as patients transition into adulthood. Koselugo is an oral MEK inhibitor that works by blocking overactive MEK1 and MEK2 enzymes involved in tumor growth in NF1 patients. The US marketing authorization holder (MAH) for Koselugo (selumetinib) is AstraZeneca Pharmaceuticals LP, with regulatory oversight and commercialization under Alexion, AstraZeneca Rare Disease, a part of the AstraZeneca group of companies.
The approval was based on results from the KOMET trial (NCT04924608), a global, randomized, double-blind, placebo-controlled Phase 3 study involving 145 adult NF1 patients with symptomatic, inoperable PN. The trial demonstrated a confirmed objective response rate (ORR) of 20% for patients treated with Koselugo versus 5% for placebo, along with durable responses lasting six months or more in most responders. The trial also showed improvements in tumor shrinkage and pain relief, highlighting Koselugo’s clinical benefit in this underserved patient population.
The data from the KOMET trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in The Lancet.
Koselugo prescribing information includes important safety warnings for potential side effects such as left ventricular dysfunction, ocular toxicity, gastrointestinal and skin toxicities, increased creatine phosphokinase, and bleeding risks. The safety profile observed in adults was consistent with that previously seen in pediatric patients, with no new safety signals. Patients are advised to be monitored carefully during treatment.
By expanding Koselugo approval to adults, patients with NF1 now have an FDA-approved targeted therapy option to manage symptomatic, inoperable plexiform neurofibromas well into adulthood. This approval also supports seamless long-term treatment, which is critical given the chronic nature of NF1 tumors that can cause disfigurement, pain, and functional impairments. Koselugo remains the first and only FDA-approved targeted therapy for this condition.
Key details about Koselugo:
Approved indication: Adults with NF1 and symptomatic, inoperable plexiform neurofibromas
Mechanism: Oral MEK1/MEK2 inhibitor targeting tumor growth pathways
Clinical evidence: Phase 3 KOMET trial, 20% ORR vs placebo 5%
Safety: Consistent with known profile, with several important warnings
Prof. Pierre Wolkenstein, MD, PhD said The KOMET Phase III trial confirms Koselugo’s potential to address the clinical burdens of plexiform neurofibromas in adults, reaffirming its role as a strong treatment option for both adult and pediatric NF1 patients.
Marc Dunoyer, CEO of Alexion said The expanded approval of Koselugo’s for adults, alongside the new pediatric granule formulation, provides essential continuity of care across the NF1 treatment journey in the US and establishes Koselugo’s as the first approved therapy for NF1 plexiform neurofibromas.
The FDA approval for adults marks a major milestone, demonstrating tangible progress in NF1 research and treatment, and offers new hope for adult patients benefiting from therapies previously available only to children stated by Annette Bakker, PhD, CEO of Children’s Tumor Foundation.
This approval reflects ongoing progress in developing precision therapies for rare genetic tumor disorders like NF1 and offers hope for improved quality of life for adult patients affected by this debilitating disease.
References
Koselugo approved in the US for adults with neurofibromatosis type 1, 20 November 2025, Astra Zeneca, https://www.astrazeneca.com/media-centre/press-releases/2025/koselugo-selumetinib-approved-in-the-us.html
Chen, Alice PLee, Alexander 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, The Lancet, Volume 405, Issue 10496, 2217 – 2230, DOI: 10.1016/S0140-6736(25)00986-9
Efficacy and Safety of Selumetinib in Adults with NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET), ClinicalTrials.gov ID NCT04924608, https://clinicaltrials.gov/study/NCT04924608
Alice P. Chen 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 43, 3014-3014(2025), DOI:10.1200/JCO.2025.43.16_suppl.3014