Alexion, AstraZeneca Rare Disease's Koselugo (selumetinib), an oral, selective MEK inhibitor, has been approved in Canada for the treatment of adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). The approval by Health Canada was based on positive results from KOMET, the largest and only placebo-controlled global Phase III trial in this patient population. Data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet.
In the primary analysis of the trial, Koselugo showed a statistically significant objective response rate (ORR) of 20% (n=14/71, 95% CI: 11.2, 30.9) compared to 5% with placebo (n=4/74, 95% CI: 1.5, 13.3; p=0.01) by cycle 16. After 12 cycles, patients on placebo were switched to Koselugo and patients on Koselugo remained on treatment for an additional 12 cycles. The safety profile of Koselugo in the KOMET Phase III trial was consistent with its known profile and established use in paediatric patients.
Koselugo has been recently approved in the US, EU, Japan and other countries for the treatment of adult patients with NF1 who have symptomatic, inoperable PN based on data from the KOMET Phase III trial, and additional regulatory reviews are ongoing. KOMET is a global Phase III randomized, double-blind, placebo-controlled, multicentre trial designed to evaluate the efficacy and safety of Koselugo in adults with NF1 who have symptomatic, inoperable PN. The trial enrolled 145 adults from 13 countries across North America, South America, Europe, Asia and Australia, with participants' baseline characteristics, including gender and distribution of PN, reflective of the global adult NF1 patient population.
Patients were enrolled and randomized to receive Koselugo or placebo (1:1) for 12 28-day cycles. Participants were required to have diagnosis of NF1, at least one symptomatic, inoperable PN measurable by volumetric MRI analysis, chronic PN pain score documented during screening, adequate organ and marrow function and stable chronic PN pain medication use at enrolment. The primary endpoint is confirmed objective response rate (ORR) by cycle 16 as assessed by ICR.
ORR is defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumour volume). Secondary endpoints include improved PN-related pain and health-related quality of life (HRQoL) at cycle 12. After 12 cycles, patients on placebo were switched to Koselugo and patients on Koselugo remained on treatment for an additional 12 cycles.
Patients who had the opportunity to complete 24 cycles of treatment have the option to participate in a long-term extension period and continue to receive Koselugo. Koselugo (selumetinib) is a kinase inhibitor that blocks specific enzymes (MEK1 and MEK2), which are involved in stimulating cells to grow. In NF1, these enzymes are overactive, causing tumour cells to grow in an unregulated way creating so-called plexiform neurofibromas (PN).
By blocking these enzymes, Koselugo slows down the growth of tumour cells and, therefore, the PN growth. Koselugo is approved in the US, EU, Japan, China and other countries for the treatment of certain paediatric patients with NF1 who have symptomatic, inoperable PN. Koselugo is approved in the US, EU, Japan and other countries for the treatment of adult patients with NF1 who have symptomatic, inoperable PN, and additional regulatory reviews are ongoing.
Koselugo has been granted Orphan Drug Designation in the US, EU, Japan and other countries for the treatment of NF1.
