12 November 2024
Koselugo showed statistically significant and clinically meaningful objective response rate vs. placebo in adults with neurofibromatosis type 1 in global KOMET Phase III trial
Results demonstrated reduction in tumour volume, building on established safety and efficacy profile of Koselugo in children and supporting expanded use in adults
Positive high-level results of KOMET, the largest, global randomised double-blind placebo-controlled multicentre Phase III trial in adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN), showed that Koselugo (selumetinib), an oral, selective MEK inhibitor, met its primary endpoint, demonstrating a statistically significant and clinically meaningful objective response rate (ORR) versus placebo in these adult patients.
NF1 is a rare, progressive genetic condition affecting an estimated 1.7 million individuals worldwide, approximately 70% of whom are adults.1,2 In 30-50% of patients, tumours develop on the nerve sheaths and may cause debilitating symptoms.3-8 NF1 is usually diagnosed in early childhood, however, NF1 often progresses into adulthood.9,10 There are no approved treatments for adults, leaving many to experience disfigurement, dysfunction, persistent pain or endure multiple surgeries.11
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, said: “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.”
Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “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 living with this debilitating disease. We look forward to sharing these findings with regulatory authorities.”
Scot Ebbinghaus, MD, Vice President, Global Clinical Development, MSD Research Laboratories, said: “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 to also treat adult patients living with this rare and challenging genetic condition.”
In the trial, ORR was defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumour volume) by cycle 16 (28 days per cycle) as determined by independent central review (ICR) per response evaluation in neurofibromatosis and schwannomatosis (REiNS) criteria.
The safety profile of Koselugo in this study was consistent with that observed in clinical trials among children and adolescents. No new safety signals were identified.
Alexion, AstraZeneca Rare Disease will share these data with regulatory authorities and present at a forthcoming medical meeting. AstraZeneca and MSD are jointly developing and commercialising Koselugo globally.