AstraZeneca and Merck (known as MSD outside the US and Canada) have announced positive results from the Phase 3 KOMET trial, evaluating Koselugo (selumetinib) in adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PNs). NF1 is a rare genetic condition affecting an estimated 1.7 million people globally. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in objective response rate compared to placebo.
KOMET Trial Results
The KOMET trial focused on patients with PNs, tumors that develop on nerve sheaths and can cause disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder or bowel dysfunction in up to 50% of NF1 patients. The primary endpoint was defined as the percentage of patients whose PNs disappeared or achieved at least a 20% reduction in tumor volume by cycle 16.
Koselugo demonstrated a statistically significant improvement in objective response rate versus placebo. The safety profile of Koselugo in the adult population was consistent with that observed in previous clinical trials involving children and adolescents, with no new safety signals identified.
Mechanism of Action
Koselugo is designed to block the MEK1 and MEK2 enzymes, which are involved in stimulating cell growth and are overactive in NF1. The drug is already approved for treating certain pediatric NF1 patients with symptomatic, inoperable PNs. Currently, there are no approved treatments specifically for adult patients with this condition.
Implications for NF1 Treatment
Marc Dunoyer, CEO of Alexion, AstraZeneca’s rare disease unit, stated that these results indicate Koselugo's potential to benefit adult patients, for whom there are currently no approved targeted therapies. Scot Ebbinghaus, vice president, global clinical development, MSD Research Laboratories, emphasized the critical need for treatment options for adults with NF1 to manage symptomatic, inoperable PNs.
The data from the KOMET trial will be shared with regulatory authorities and presented at an upcoming medical meeting. This could potentially expand the use of Koselugo beyond pediatric patients to include adults living with this rare genetic condition.
