FDA Approves Selumetinib for Pediatric Neurofibromatosis Type 1 Plexiform Neurofibromas

The FDA has approved selumetinib for the treatment of pediatric patients, aged 2 years and above, with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas.

The FDA has approved selumetinib (Koselugo) for the treatment of pediatric patients, aged 2 years and above, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).1

This represents the first medicine approved to treat NF1 PN, a rare and debilitating genetic condition.

“Previously there were no medicines approved for this disease. This approval has the potential to change how symptomatic, inoperable NF1 plexiform neurofibromas are treated and provides new hope for these patients,” Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, MSD Research Laboratories, said in a statement.

Findings from the phase II SPRINT Stratum 1 trial supported the approval. The National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)—sponsored trial showed that the MEK1/2 inhibitor induced an overall response rate of 66% in pediatric patients with NF1 PN.

The open-label trial enrolled patients aged 2 to 18 years with NF1 and inoperable, measurable PN who were able to swallow capsules. The trial divided patients between 2 strata: one for patients with at least one neurofibroma-related complication, and the second for patients with no clinically significant complications but the potential for the development of a complication.

Findings from Stratum 1, which led to the FDA approval, were published in theNew England Journal of Medicine.2

Patients received continuous twice-daily oral selumetinib at 25 mg/m2in 28-day cycles. Treatment continued for up to 2 years unless a partial response was reported or if the patient had progressive disease at baseline, these patients were able to continue treatment beyond 2 years.

Fifty patients were included in Stratum 1 with a median age of 10.2 years (range, 3.5-17.4). Forty-two percent of patients had progressive neurofibromas at baseline. Patients had a median of 3 neurofibroma-related complications (range, 1-5) with disfigurement (88%), motor dysfunction (66%), and pain (52%) being the most common.

Confirmed partial responses were seen in 70% of patients with durable responses in 56%. The median time to first response and best response were 8 and 16 cycles, respectively. At best response, the median change in neurofibromas volume was —27.9% (range, –55.1% to 2.2%).

The median progression-free survival (PFS) was not reached, but at 3 years the PFS rate was 84%.

As of data cutoff, 23 patients maintained their partial response and 21 had discontinued treatment due to progressive disease (n = 5), stable disease (n = 2), adverse effects (AEs; n = 5), or other reasons.

Changes in the size of the patients’ neurofibromas were compared with the growth of age-matched patients who did not receive selumetinib. Seventy-eight percent of 93 age-matched controls demonstrated an increase of at least 20% in the same period of time and had a median PFS of 1.3 years. None of the age-matched controls showed tumor shrinkage of more than 20%.

Sixty-eight percent of patients had some degree of improvement in functional outcome measures over time based on serial patient-reported outcome measurements. After a year of treatment, patients evaluable for pain showed a mean change in tumor pain intensity of —2.14 points with a decrease in intensity beginning as early as 2 months after initiation of treatment. The mean total quality-of-life score improved by 6.7 points on child-reported measures and 13.0 points on parent-reported measures by Pediatric Quality of Life Inventory Generic Core Scales. At 12 months of treatment, 72% of children and 86% of parents reported some improvement in tumor-related problems.

“Koselugo has made a difference for many children in this trial. This is an important treatment advance for patients and their families,” Brigitte C. Widemann, MD, principal investigator of the SPRINT trial and chief, NCI Pediatric Oncology Branch, said in a statement.

Selumetinib is being jointly developed and commercialized globally by AstraZeneca and Merck. A marketing authorization application for selumetinib in this setting was also submitted to the European Medicines Agency in the first quarter of the year, and further global regulatory submissions are being considered.1

The agent previously received an orphan drug designation from the FDA in February 2018, a breakthrough therapy designation in April 2019, and a rare pediatric disease designation in December 2019.


  1. Koselugo (selumetinib) approved in US for paediatric patients with neurofibromatosis type 1 plexiform neurofibromas [press release]. Kenilworth, NJ: AstraZeneca and MSD; April 13, 2020. https://bit.ly/2Xwk821. Accessed April 13, 2020.
  2. Gross AM, Wolters P, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas.N Engl J Med. 2020;382:1430-1442. doi: 10.1056/NEJMoa1912735.
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