Rare Daily Staff

AstraZeneca and Merck reported that the U.S. Food and Drug Administration has accepted a New Drug Application (NDA) and granted Priority Review for selumetinib as a potential new medicine for pediatric patients aged three years and older with the rare genetic condition neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gnee and is associated with many symptoms, including soft lumps on and under the skin, skin pigmentation, and it about 30 to 50 percent of patients, tumors on the nerve sheaths called plexiform neurofibromas (PNs). These PNs can cause pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction, and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumors. It is incurable and affects on in every 3,000 to 4,000 individuals.

People with NF1 may experience a number of complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. NF1 also increases a person’s risk of developing other cancers, including malignant brain and peripheral nerve sheath tumors, and leukemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.

This is the first acceptance of a regulatory submission for an oral monotherapy for the treatment of NF1. A regulatory review date is set for the second quarter of 2020.

The regulatory submission was based on positive results from the National Cancer Institute Cancer Therapy Evaluation Program-sponsored phase 2 in which an objective response rate was achieved in 66 percent of pediatric patients with NF1 and symptomatic, inoperable PNs when treated with selumetinib as a twice-daily oral monotherapy. It was defined as the percentage of patients with a confirmed complete or partial response of  greater than or equal to 20 percent tumor volume reduction.

Selumetinib is a MEK 1/2 inhibitor designed to inhibit the MEK enzyme in the RAS/MAPK cell-signaling pathway associated with cancer cell growth and proliferation in a number of different tumor types. It was granted FDA Breakthrough Therapy designation in April 2019, Orphan Drug designation in February 2018, EU Orphan designation in August 2018 and Swissmedic Orphan Drug status in December 2018.

Photo: PDUFA–FDA, Rare Disease

X