Koselugo Meets Primary Endpoint in Phase III KOMET Trial for Adult NF1 Patients
Key Insights
Koselugo (selumetinib) demonstrated a statistically significant and clinically meaningful objective response rate (ORR) versus placebo in adult patients with neurofibromatosis type 1 (search) (NF1) and symptomatic, inoperable plexiform neurofibromas (search) (PN).
The KOMET trial is the largest global, randomized, double-blind, placebo-controlled Phase III trial conducted in adults with NF1 PN.
The safety profile of Koselugo in the KOMET trial was consistent with previous studies in children and adolescents, with no new safety signals identified.
The Phase III KOMET trial of Koselugo (selumetinib) has met its primary endpoint, demonstrating a statistically significant and clinically meaningful objective response rate (ORR) compared to placebo in adult patients with neurofibromatosis type 1 (search) (NF1) and symptomatic, inoperable plexiform neurofibromas (search) (PN). These results offer a potential new treatment option for adult patients with NF1 PN, a population with limited approved therapies.
KOMET Trial Details
The KOMET trial is a global, randomized, double-blind, placebo-controlled, multicenter Phase III study. It enrolled 145 adults with NF1 from 13 countries. Participants were randomized 1:1 to receive either Koselugo or placebo for 12 cycles (28 days per cycle). After 12 cycles, patients on placebo were switched to Koselugo. The primary endpoint was confirmed ORR by cycle 16, as assessed by independent central review (ICR) using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. ORR was defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumor volume).
Clinical Significance
NF1 is a rare, progressive genetic condition affecting an estimated 1.7 million individuals worldwide, with approximately 70% being adults. Between 30% and 50% of these patients develop tumors on the nerve sheaths (PNs), which can lead to disfigurement, motor dysfunction, pain, and other clinical issues. Currently, there are no approved treatments for adults with NF1 PN in many regions, highlighting a significant unmet medical need.
Professor Ignacio Blanco Guillermo, MD, PhD, a principal investigator in the KOMET trial, noted the potential impact of these findings: "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 (search)."
Safety Profile
The safety profile of Koselugo in the KOMET trial was consistent with previous clinical trials involving children and adolescents. No new safety signals were identified, reinforcing the established safety profile of the drug.
Future Steps
Alexion, AstraZeneca Rare Disease (search), intends to share these data with regulatory authorities and present the findings at an upcoming medical meeting. This could potentially expand the approved use of Koselugo to include adult patients with NF1 PN.
Marc Dunoyer, chief executive officer, Alexion, AstraZeneca Rare Disease (search), stated, "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."
About Koselugo
Koselugo (selumetinib) is a kinase inhibitor that targets MEK1 (search) and MEK2 (search) enzymes, which are involved in stimulating cell growth. In NF1, these enzymes are overactive, leading to unregulated tumor cell growth and the formation of plexiform neurofibromas (search) (PNs). By blocking these enzymes, Koselugo slows down the growth of tumor cells and, consequently, PN growth. Koselugo is currently approved in the US, EU, Japan, China, and other countries for the treatment of certain pediatric patients with NF1 who have symptomatic, inoperable PNs. AstraZeneca and MSD are jointly developing and commercializing Koselugo globally.