Selumetinib sulfate

AstraZeneca (AZ) and Merck – known as MSD outside the US and Canada – have shared positive results from a late-stage study of Koselugo (selumetinib) in adults with neurofibromatosis type 1 (NF1), rare genetic condition affecting an estimated 1.7 million people globally. The phase 3 KOMET trial has been evaluating the oral MEK inhibitor in NF1 patients who have symptomatic, inoperable plexiform neurofibromas (PNs). In up to 50% of NF1 patients, tumours develop on the nerve sheaths (PNs) and cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bladder or bowel dysfunction. KOMET met its primary endpoint, with Koselugo demonstrating a statistically significant and clinically meaningful improvement in objective response rate versus placebo. This was defined as the percentage of patients whose PNs disappeared or achieved at least a 20% reduction in tumour volume by cycle 16. The safety profile of Koselugo was also shown to be consistent with that observed in clinical trials among children and adolescents, with no new safety signals identified. Koselugo is designed to block the MEK1 and MEK2 enzymes, which are involved in stimulating cells to grow and are overactive in NF1. The drug already holds approvals to treat certain paediatric NF1 patients who have symptomatic, inoperable PNs, but there are currently no approved treatments for adult patients. Marc Dunoyer, chief executive officer of Alexion, AZ’s rare disease unit, said: “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.” Scot Ebbinghaus, vice president, global clinical development, MSD Research Laboratories, added: “Adults with NF1 are in critical need of treatment options to help manage symptomatic, inoperable PNs. “These positive results from the phase 3 KOMET trial demonstrate the potential to expand the use of Koselugo beyond paediatric patients to also treat adult patients living with this rare and challenging genetic condition.” The new data for Koselugo will now be shared with regulatory authorities and presented at a future medical meeting.

Merck and AstraZeneca are hoping to expand the label of their MEK inhibitor Koselugo to certain adult patients with neurofibromatosis type 1 following a successful Phase 3 study. The companies announced Tuesday that Koselugo showed a “statistically significant and clinically meaningful” improvement in response rate compared with placebo in adult patients, meeting the KOMET study’s primary endpoint. The pivotal trial included 145 adults with symptomatic and inoperable plexiform neurofibromas. AstraZeneca’s rare disease subsidiary Alexion will bring the data to regulators and present them at a future medical meeting, according to the press release. The drug was approved in 2020 for certain pediatric patients 2 years and older with the genetic disease, which causes benign tumors to grow along the nerves. In neurofibromatosis type 1, the enzymes MEK1 and MEK2 are overactive and cause the cells to grow into noncancerous tumors called plexiform neurofibromas around the nerves. Koselugo blocks those enzymes in hopes of slowing down the growth of those tumors. AstraZeneca licensed Koselugo (selumetinib) from Array BioPharma in 2003, but the drug failed several cancer studies. The UK pharma included the drug in an $8.4 billion co-development pact with Merck in 2017 that also included Lynparza.