▎WuXiEdited by Kant Content Team

Today, AstraZeneca and MSD jointly announced positive topline results from the KOMET Phase 3 clinical trial. Analysis shows that Koselugo (selumetinib), co-developed by the two companies for treating adult patients with symptomatic, inoperable plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1), significantly reduced tumor volume, achieving the primary endpoint of the trial.

NF1 is a rare, incurable genetic disorder.NF1 is caused by the synthesis of neurofibromin.NF1Caused by gene mutations.This gene mutation can disrupt the RAS/MAPK signaling pathway (RAS-RAF-MEK-ERK), leading to tumor growth.Symptoms of NF1 include soft lumps on and under the skin (cutaneous neurofibromas) and skin pigmentation deposits (referred to as "café-au-lait spots").In 20-50% of NF1 patients, tumors develop on the nerve sheath, leading to PN.These PNs can cause pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction, and disfigurement, with the potential to transform into malignant peripheral nerve sheath tumors (MPNST).

KOMET is a global, randomized, double-blind, placebo-controlled, multicenter Phase 3 trial designed to evaluate the efficacy and safety of Koselugo in adult NF1 patients with symptomatic, inoperable plexiform neurofibromas.The results showed that, in these adult patients, Koselugo demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of objective response rate (ORR) compared to placebo.In the trial, ORR is defined as the percentage of patients with complete response (PN disappearance) or partial response (tumor volume reduction of at least 20%) confirmed by Independent Central Review (ICR) according to the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria at Cycle 16 (each cycle is 28 days).

The safety of Koselugo in this study was consistent with that observed in clinical trials involving children and adolescents.No new safety issues were found.

MEK is a key protein kinase in the RAS/MAPK signaling pathway.Koselugo can selectively inhibit MEK1 and MEK2, restoring the dysfunctional signaling pathway to normal and thereby alleviating the condition of NF1 patients.Koselugo has been granted Orphan Drug Designation, Breakthrough Therapy Designation, and Priority Review by the FDA for the treatment of NF1.

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References:

[1] KOSELUGO® (selumetinib) Showed Significant and Clinically Meaningful Improvement in Objective Response Rate Versus Placebo in Adults With Neurofibromatosis Type 1 who Have Symptomatic, Inoperable Plexiform Neurofibromas in Global Phase 3 KOMET Trial. Retrieved November 12, 2024 from https://www.merck.com/news/koselugo-selumetinib-showed-significant-and-clinically-meaningful-improvement-in-objective-response-rate-versus-placebo-in-adults-with-neurofibromatosis-type-1-who-have-symptomatic-inoperable/

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