Potential NF1 Therapy Gets Orphan Drug Designation

On Thursday, AstraZeneca and Merck announced that selumetinib, its MEK 1/2 inhibitor for the treatment of neurofibromatosis type 1 (NF1), was granted orphan drug designation by the U.S. Food and Drug Administration (FDA).

Selumetinib is oral and highly selective, and is being developed to inhibit MEK 1/2.

NF1 — or von Recklinghausen’s disease – is a rare genetic disorder characterized by the development of multiple benign, or noncancerous, tumors or nerves and skin. At present, it is incurable and occurs 1 in every 3,000 births with variable symptoms that can affect the skin, skeleton and nervous system.

In addition to its initial presentation, NF1 can also cause secondary complications, including learning difficulties, visual impairment, pain, disfigurement, twisting and curvature of the spine, high blood pressure and epilepsy.

In a press release, Sean Bohen, executive vice president or global medicines development and chief medical officer of AstraZeneca stressed the unmet need for NF1 patients: “Neurofibromatosis type 1 is a devastating condition that can lead to life-threatening complications. There is no known cure for neurofibromatosis and there are limited treatment options to manage symptoms.”

The NF1 gene codes for a protein called Neurofibromin, which negatively regulates the RAS/MAPK pathway, partly responsible for controlling cell growth, differentiation and survival. Mutations in the gene may cause the growth of cancerous cells, resulting in the development of tumors.

Approximately 20% to 50% of NF1 patients experience plexiform neurofibromas (PNs). PNs are tumors that arise from nerve fascicles and tend to grow along the length of the nerve and cause pain, motor dysfunction and disfigurement. Selumetinib, potentially, could alleviate symptoms in pediatric patients with NF1-related PNs. The possible benefit is currently being studied in a phase 1/2 trial (SPRINT), sponsored by the U.S. National Cancer Institute (NCI).

“This is an important collaborative effort with our colleagues at AstraZeneca addressing an area of significant unmet medical need to potentially benefit patients with neurofibromatosis type 1,” said Dr Roy Baynes, senior vice president and head of global clinical development, chief medical officer of Merck Research Laboratories.

Patients with NF1 have an increased risk of developing other cancers, including malignant brain and peripheral nerve sheath tumors and leukemia. Symptoms have been reported to reduce life expectancy by up to 15 years.

Selumitinib was licensed by AstraZeneca from Array BioPharma Inc. in 2003, and is also being investigated in the Phase 3 ASTRA trial of patients who are diagnosed with differentiated thyroid cancer (DTC) following surgery and radioactive iodine. It was granted orphan drug designation for that indication in 2016.

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