AMC team proves new neurofibromatosis drug selumetinib’s effects in adult patients for 1st time worldwide

The efficacy of selumetinib for treating plexiform neurofibromas, the most representative symptom of the rare inherited disease neurofibromatosis, has been confirmed in Korean patients.

This is the first time in the world that selumetinib is effective in adult patients.

Neurofibromatosis is a rare disease caused by genetic factors and is a neurocutaneous syndrome characterized by abnormalities in the skin and central nervous system. Among the various neurofibromatosis subtypes, neurofibromatosis type 1 is the most common, affecting about one in 3,000 people. It is estimated that there are about 10,000 patients in Korea.

Plexiform neurofibromas, irregularly shaped hard masses, are a typical symptom of neurofibromatosis type 1. Most are treated with selumetinib, an expensive drug used for difficult-to-operate patients. For the first time, the results of a study on selumetinib in Korean patients have been published.

Asan Medical Center (AMC) said Thursday that a research team analyzed the outcomes of 89 patients treated with selumetinib for neurofibromatosis type 1 and plexiform neurofibromas between May 2019 and December 2021, up to 104 weeks after treatment, and found that plexiform neurofibromas decreased in size by an average of about 41 percent.

The team comprised Professor Lee Beom-hee of the Medical Genetics Center, Professor Na Young-shin of the Department of Pediatric Neurosurgery, Professor Kym Hye-ry of the Department of Pediatric Hematology and Oncology, and Professor Yoon Hee-mang of the Department of Radiology,

Eighty-eight of 89 patients (98.9 percent) had an average reduction of 40.8 percent in their plexiform neurofibromas. One patient did not respond to treatment. Eighty-one (91 percent) patients had a “partial response,” meaning a reduction in tumor size of 20 percent or more.

Of the 89 patients, 59 pediatric patients under 19 had an average reduction of about 39 percent in the size of their plexiform neurofibromas, and 30 adults over 19 had a reduction of about 42 percent.

In addition to tumor size reduction, the researchers presented the first analysis of selumetinib's effect on neurocognitive decline, café au lait spots, and slowed growth, which can be seen in neurofibromatosis.

Neurocognitive function tests using the Wechsler test showed significant improvements in verbal comprehension in pediatric patients, perceptual reasoning in pediatric and adult patients, and intelligence quotient in both pediatric and adult patients, with café au lait spots lightening by more than 30 percent.

Plexiform neurofibromas in half of patients with neurofibromatosis type 1 are irregular, non-hard fibromas shown in clusters along nerves. They often occur in the skin of the face or near spinal nerves, causing disfigurement, compression of nearby organs, and pain. Some may become malignant.

Before the development of selumetinib, there was no way to treat the disease, but the U.S. Food and Drug Administration (FDA) approved it in 2020 for pediatric patients. In Korea, the Ministry of Food and Drug Safety approved it for use in 2021, and health insurance coverage was applied for last year.

The health insurance coverage process was based on the research team's interim findings, and the results were recently published in a paper.

“The results of this study could be produced thanks to the multidisciplinary rare disease treatment system at Asan Medical Center,” Professor Lee said. “Currently, selumetinib is covered by health insurance only for pediatric plexiform neurofibroma patients, but this study has demonstrated the effectiveness and safety of the treatment in adult patients, so it is necessary to expand the scope of coverage.”