Merck & Co (MSD), along with Alexion and AstraZeneca Rare Disease, announced positive topline results from the Phase III KOMET trial, evaluating Koselugo (selumetinib) for adult patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PN). The global, multi-center, double-blind, placebo-controlled study demonstrated a statistically significant and clinically meaningful improvement in the objective response rate (ORR) compared to placebo.
The KOMET trial enrolled 145 adult participants from 13 countries across Australia, Asia, South America, Europe, and the US. Participants had to have at least one symptomatic and inoperable PN, measurable by volumetric magnetic resonance imaging (MRI) analysis. The primary endpoint was the ORR, defined as the percentage of patients with a confirmed complete or partial response by cycle 16, assessed by independent central review (ICR) based on response evaluation in neurofibromatosis and schwannomatosis (REiNS) criteria.
Clinical Efficacy and Safety
The trial's primary endpoint, objective response rate (ORR), exhibited a statistically significant and clinically meaningful improvement in patients treated with Koselugo compared to placebo. The safety profile of Koselugo in this trial was consistent with that observed in previous clinical trials involving pediatric and adolescent patients, with no new safety signals identified.
Current Treatment Landscape and Unmet Needs
NF1 is a genetic disorder characterized by the growth of tumors along nerves throughout the body. Plexiform neurofibromas (PNs) can cause significant morbidity, including pain, disfigurement, and functional impairment. While Koselugo is approved for pediatric patients with NF1 and PNs, there are currently no approved targeted therapies for adult patients, highlighting a significant unmet medical need.
Regulatory Implications and Future Directions
Koselugo is already approved in the US, European Union, China, and Japan for pediatric patients with NF1 PN and has received orphan drug status in these regions. Alexion CEO Marc Dunoyer stated, "These promising results demonstrate that Koselugo, the first and only approved targeted therapy for certain children with NF1 plexiform neurofibromas, now has the potential to benefit adult patients, for whom there are no approved targeted therapies."
Dunoyer added, "As the largest and only global placebo-controlled Phase III trial in adults with NF1 plexiform neurofibromas, 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."
