Failed as a Cancer Treatment - Selumetinib Granted Orphan Designation in Europe for Neurofibromatosis Type 1

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  • Selumetinib granted Orphan Status by the FDA in 2018
  • NF1 gene mutation occurs in approximately one in 3,000 births
  • Array Biopharma claims AZ owes approximately $192 million in unpaid royalty fees related to selumetinib agreement


AstraZeneca and Merck (NYSE:MRK) announced on 8/3/18 that the European Medicines Agency (EMA) has granted orphan designation to selumetinib, a MEK 1/2 inhibitor, for the treatment of neurofibromatosis type 1 (NF1). Selumetinib was granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of NF1 in February 2018.

NF1 is an incurable genetic condition that affects one in 3,000 newborns worldwide. The severity of signs and symptoms associated with NF1 can be highly variable, are often mild-to-moderate and may include skin, nerve and skeletal manifestations. Plexiform neurofibromas (PNs) are benign tumors on nerve sheaths that develop in 20-50 percent of patients and, as they continue to increase in number and size, cause moderate-to-severe morbidities such as pain, motor dysfunction and disfigurement.

Sean Bohen, executive vice president, global medicines development and chief medical officer, at AstraZeneca, said, “There is no cure for NF1, a life-long and devastating condition, and current treatment choices for these patients are very limited. The granting of an orphan designation is a positive step forward for children with NF1 and their families.”

The potential benefit of selumetinib in NF1 is being explored in the Phase 1/2 SPRINT trial in pediatric patients with inoperable NF1-related PNs. Select findings were presented recently at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago by the principal investigators at the National Cancer Institute (NCI). Full results are expected later in 2018.

NF1 is caused by a spontaneous or inherited mutation in the NF1 gene and affects approximately one in 3,000 births. 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, benign tumors on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause morbidities such as pain, motor dysfunction and disfigurement.

Selumetinib has previously failed in trials as a cancer treatment. In 2016 the drug failed to improve progression free survival in patients with KRAS mutation-positive non-small cell lung cancer (NSCLC). In July of 2018, AstraZeneca announced that  selumetinib had failed a trial for thyroid cancer.

AstraZeneca licensed the drug from Array Biopharma in 2003. Array claimed earlier this year that it was owed $192 million in unpaid royalty fees related to AZ's sub-licensing deal with Merck.