Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation to AstraZeneca and Merck’s experimental drug selumetinib for the treatment of pediatric patients aged 3 and older with neurofibromatosis type 1, a rare, incurable, genetic condition.

Neurofibromatosis type 1 (NF1) is caused by a spontaneous or inherited mutation in the NF1 gene. In 20 to 50 percent of patients, tumors develop on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause clinical issues, such as pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumors.


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 tumors, malignant peripheral nerve sheath tumor, and leukemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.

“This new designation validates our ongoing development of selumetinib,” said Roy Baynes, head of global clinical development and chief medical officer at Merck’s MSD Research Laboratories. “As a result of this, selumetinib has the potential to receive expedited regulatory review and we hope to bring this medicine to patients as soon as possible.”

The NF1 gene provides instructions for making a protein called neurofibromin, which negatively regulates the RAS/MAPK pathway, helping to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulations 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.

The Breakthrough Therapy designation is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which may demonstrate substantial improvement on a clinically-significant endpoint over available medicines.

The FDA granted the designation to selumetinib based on phase 2 data from the SPRINT trial, which is testing selumetinib as an oral monotherapy in pediatric patients with inoperable NF1-related plexiform neurofibromas.

Selumetinib was licensed by AstraZeneca from Array BioPharma in 2003, and in 2017, AstraZeneca and Merck entered a co-development and co-commercialization agreement for the compound as part of their collaboration around the PARP inhibitor Lynparza. Working together, the companies agreed to develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

The FDA and European Medicines Agency have previously granted Selumetinib Orphan Drug designation for the treatment of NF1. It is currently being assessed as a monotherapy and in combination with other treatments in ongoing trials.

Photo: Roy Baynes, head of global clinical development and chief medical officer at MSD Research Laboratories