Koselugo (selumetinib) Shows Notable Improvement in Objective Response Rate Versus Placebo for Adults with Neurofibromatosis Type 1 and Symptomatic, Inoperable Plexiform Neurofibromas in Global KOMET Study
The KOMET Phase 3 trial results demonstrated a significant reduction in tumor size, highlighting Koselugo's established efficacy and safety profile in certain pediatric cases and its potential for adult application.
Alexion, AstraZeneca Rare Disease, in partnership with Merck, announced positive topline results from the Phase 3 KOMET study. This study is the largest global, randomized, double-blind, placebo-controlled Phase 3 trial focused on adults with neurofibromatosis type 1 (NF1) who suffer from symptomatic, inoperable plexiform neurofibromas (PN). The results revealed that Koselugo, an oral MEK inhibitor, led to a statistically significant and clinically meaningful improvement in objective response rate (ORR) over placebo, which served as the primary endpoint of the study.
Neurofibromatosis type 1 is a rare, progressive genetic disorder that affects an estimated 1.7 million people globally, with around 70% of these being adults. In 30-50% of cases, individuals develop tumors along nerve sheaths, resulting in symptoms that can be severely debilitating. Typically diagnosed in early childhood, NF1 can progress into adulthood. Currently, no approved treatments exist for adults, leaving many to face symptoms such as pain, functional impairment, and the possibility of repeated surgeries.
In this study, ORR was defined as the percentage of participants achieving a confirmed complete response (PNs fully disappeared) or a partial response (at least 20% reduction in tumor volume) by cycle 16 (28 days per cycle), as evaluated by an independent central review (ICR) using the response evaluation in neurofibromatosis and schwannomatosis (REiNS) criteria.
The safety profile of Koselugo in adults mirrored results from prior clinical trials in children and adolescents, with no new safety concerns observed.
Alexion and AstraZeneca intend to submit this data to regulatory authorities and present further findings at an upcoming medical conference. Koselugo is being co-developed and marketed globally by AstraZeneca and Merck.
About the KOMET Study
KOMET is a Phase 3 global, randomized, double-blind, placebo-controlled, multi-center trial evaluating the efficacy and safety of Koselugo in adults with NF1 who have symptomatic, inoperable PNs. This study included 145 adults across 13 countries, including the United States, Asia, Australia, South America, and Europe. Participants were randomized 1:1 to receive either Koselugo or placebo over twelve 28-day cycles. Key inclusion criteria were a confirmed NF1 diagnosis with at least one symptomatic, inoperable target PN measurable via MRI, documented chronic PN pain, stable pain medication, and sufficient organ and bone marrow function.
The trial’s primary endpoint was confirmed ORR by cycle 16, as evaluated by ICR, with ORR defined as the percentage of patients who achieved a complete response or a partial response of at least 20% tumor reduction.
Following the 12 cycles, placebo participants were switched to Koselugo treatment, while those on Koselugo continued for an additional 12 cycles. Patients completing both treatment phases had the option to enroll in a long-term extension period with continued KOSELUGO administration.
About Neurofibromatosis Type 1 (NF1)
NF1 is a rare genetic disorder caused by mutations in the NF1 gene, either inherited or occurring spontaneously. Symptoms include benign lumps on or under the skin (cutaneous neurofibromas), and in 30-50% of patients, PNs develop along nerve sheaths. These tumors can cause a range of clinical issues, from physical disfigurement to impaired motor skills, pain, and even organ dysfunction. Plexiform neurofibromas often begin in early childhood, vary in severity, and can potentially reduce life expectancy by as much as 15 years.
About Koselugo (selumetinib)
Koselugo is a kinase inhibitor that specifically blocks MEK1 and MEK2 enzymes, which play a role in cell growth stimulation. In NF1, these enzymes become overly active, causing uncontrolled growth of tumor cells and the formation of plexiform neurofibromas. Koselugo slows down this tumor growth by inhibiting the activity of these enzymes.
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