On February 15, 2018 -AstraZeneca and Merck (NYSE:MRK), known as MSD outside the U.S. and Canada, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for selumetinib, a MEK 1/2 inhibitor, for the treatment of neurofibromatosis type 1 (NF1) (Press release, Merck & Co, FEB 15, 2018, View Source [SID1234524008]).

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NF1 is an incurable genetic condition that affects one in 3,000 births with highly-variable symptoms including cutaneous (skin), neurological (nervous system) and orthopedic (skeletal) manifestations. NF1 can cause secondary complications including learning difficulties, visual impairment, pain, disfigurement, twisting and curvature of the spine, high blood pressure and epilepsy. Plexiform neurofibromas (PNs) are tumors that arise from nerve fascicles and tend to grow along the length of the nerve. PNs, a neurological manifestation of NF1,occur in approximately 20-50 percent of NF1 patients causing pain, motor dysfunction and disfigurement.

Sean Bohen, executive vice president, global medicines development and chief medical officer, AstraZeneca, said, "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."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "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."

The potential benefit of selumetinib in NF1 is being explored in the U.S. National Cancer Institute-sponsored phase 1/2 SPRINT trial in pediatric patients with symptomatic NF1-related PNs. Phase II trial results are expected later in 2018.

The FDA’s ODD program provides orphan status to medicines that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S.

In addition to NF1, selumetinib is being investigated in the phase 3 ASTRA trial of patients who are diagnosed with differentiated thyroid cancer (DTC) following surgery and treatment with radioactive iodine. Selumetinib was granted ODD by the US FDA for the adjuvant treatment of stage 3/4 DTC in 2016. It is also being explored as a monotherapy and in combination with other treatments in phase 1 trials.

NOTES TO EDITORS

About neurofibromatosis type 1 (NF1)

The NF1 gene provides instructions for making a protein called Neurofibromin. The disease is associated with many symptoms, including soft lumps on and under the skin (subcutaneous neurofibromas), skin pigmentation (cafe au lait spots) and, in 20-50 percent of patients, tumors on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause morbidities such as pain, motor dysfunction and disfigurement. Patients with NF1 may experience a number of other complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. People with NF1 also have an increased risk of developing other cancers, including malignant brain and peripheral nerve sheath tumors, and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.

About selumetinib

Selumetinib, is an investigational MEK 1/2 inhibitor licensed by AstraZeneca from Array BioPharma Inc. in 2003.

The NF1 gene codes for a protein called Neurofibromin. This protein negatively regulates the RAS/MAPK pathway, which helps to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulation in RAS/RAF/MEK/ERK signaling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumor growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumor growth.