In a major breakthrough, the Food and Drug Administration (FDA) has approved a treatment for a genetic disorder called neurofibromatosis type one (NF1). The disease impacts more than 2.5 million people and can cause a type of tumor growth on nerves called plexiform neurofibromas, which can be debilitating and painful. The drug, Koselugo (selumetinib) is the first treatment for NF1, and is intended for use in patients who have been tested for the disease at the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH).
Clinical trials that assessed the efficacy of the drug showed that in more than 70 percent of patients with inoperable plexiform neurofibromas, Koselugo reduced tumor size by 20 to 60 percent. There was a visual reduction in tumor size, and pain was lessened in patients, who also reported greater mobility, better physical function, and improved quality of life.
The drug is an MEK inhibitor; it targets a biochemical signaling pathway in cells called Ras/Raf/MEK/ERK, which is involved in the survival and growth of cells. MEK inhibitors have been studied as potential cancer therapeutics, and it was found that they could dramatically affect the size of NF1 tumors. The first encouraging results were reported by Dr. Brigitte Widemann at a 2015 NF Conference. Additional confirmatory studies have followed.
On a personal note, I'm thrilled to learn of this development, though it's bittersweet. My mother had NF1 and died several years ago. It's heartening, however, to hear that patients have been updated throughout the course of these clinical trials. Science and medicine have come a long way since my mother's diagnosis, when very little was known about the disease, and she was diagnosed and quickly dismissed from a doctor's office. While the hereditary nature of NF was known in the medical community by 1900, diagnostic criteria weren't set by the NIH until 1988, and the NF1 gene was not identified until 1990. By 2019, patients were being included in the FDA's first 'NF listening session.'
There are other MEK inhibitors in clinical trials now (like mirdametinib by SpringWorks Therapeutics), so patients might have more treatment options in the near future.
"We are so excited for the entire NF community today! This announcement from the FDA about Koselugo (selumetinib) is a tremendous step towards our ultimate dream - approved treatments for all forms of neurofibromatosis," said Annette Bakker, PhD, President of the Children's Tumor Foundation. "We believe that FDA approval of this treatment helps not only a subset of NF1 patients, it opens the door to increased interest in all forms of NF by pharmaceutical companies. We are already experiencing it; the number of companies interested in NF1, NF2, and schwannomatosis is growing rapidly."