KOMET Trial Shows Koselugo's Promising Results In Treating Adults With NF1 and Inoperable Plexiform Neurofibromas

The KOMET trial, the most extensive global Phase III study for adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN), has reported encouraging results. The study showed that Koselugo (selumetinib), an oral MEK inhibitor, successfully met its primary endpoint, demonstrating a significant and clinically meaningful improvement in the objective response rate (ORR) compared to a placebo in adult patients.

NF1 is a rare genetic disorder that affects about 1.7 million people worldwide, with around 70% of those impacted being adults. In 30-50% of cases, tumors develop on the nerve sheaths, leading to debilitating symptoms. While NF1 is typically diagnosed in childhood, it often worsens as patients reach adulthood. Currently, there are no approved treatments for adults, leaving many to endure disfigurement, pain, and multiple surgeries.

“With limited options to manage NF1 PN in adults, many patients experience functional impairment and symptoms, which can substantially impact their lives. These clinically meaningful data show Koselugo has the potential to make a positive impact in patient care by reducing the size of plexiform neurofibromas,” stated Prof. Ignacio Blanco Guillermo, MD, PhD, Chairman of the Genetic Counselling and Clinical Genetics Programme at the Germans Trias i Pujol University Hospital, Chairman of the Spanish National Reference Centre for Adult Patients with Neurofibromatosis and Principal Investigator of the KOMET trial.

In the KOMET trial, ORR was measured as the percentage of patients who achieved either a complete response (where PNs disappeared) or a partial response (where tumour volume was reduced by at least 20%) by the 16th cycle (28 days per cycle), based on independent central review using the REiNS criteria.

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, commented, “These promising results demonstrate that Koselugo, the first and only approved targeted therapy for certain children with NF1 PN, now has the potential to benefit adult patients for whom there are no approved targeted therapies. As the largest and only global placebo-controlled Phase III trial in adults with NF1 PN, KOMET reinforces our leadership in advancing potential treatment options for people with this debilitating disease. We look forward to sharing these findings with regulatory authorities.”

The safety profile of Koselugo in this study was consistent with what has been observed in previous clinical trials with children and adolescents, with no new safety concerns identified. Alexion, AstraZeneca Rare Disease plans to share these results with regulatory authorities and present them at an upcoming medical conference. AstraZeneca and MSD are collaborating on the global development and commercialisation of Koselugo.

Scot Ebbinghaus, MD, Vice President, Global Clinical Development, MSD Research Laboratories, also commented, “Adults with NF1 are in critical need of treatment options to help manage symptomatic, inoperable plexiform neurofibromas. These positive results from the Phase III KOMET trial demonstrate the potential to expand the use of Koselugo beyond paediatric patients and also to treat adult patients living with this rare and challenging genetic condition.”