Targeting a Genetic Disease for Pediatric Patients

The FDA has approved a molecularly targeted therapeutic for treating certain patients with neurofibromatosis type 1 who have inoperable tumors.

The U.S. Food and Drug Administration (FDA) has approved the molecularly targeted therapeutic selumetinib (Koselugo) to treat certain pediatric patients with a genetic disorder called neurofibromatosis type 1 (NF1), which causes severe symptoms and complications including a significantly increased risk for developing various types of tumors.

Tumors that develop in patients with NF1 are usually benign, but some people with the condition develop malignant tumors, usually in adolescence or adulthood. Plexiform neurofibromas are tumors that arise in cells that form the covering of peripheral nerves. These benign tumors occur in up to 50 percent of patients with NF1 and can cause pain, disability, and disfigurement. They can also go on to become cancerous.

In many cases, plexiform tumors cannot be removed through surgery and new treatment options are urgently needed. Selumetinib is the first therapeutic approved to treat pediatric patients with this disease.

Research has shown that the growth of plexiform tumors in patients with NF1 is fueled by a signaling pathway that includes proteins called MEK proteins. This led to speculation that therapeutics that target MEK proteins might provide benefit to patients with NF1. 

Selumetinib is a MEK-targeted therapeutic. It was approved by the FDA for treating pediatric patients age 2 and older who have NF1–related plexiform neurofibromas that cannot be safely removed surgically. 

The approval was based on results from the phase II SPRINT clinical trial, which was sponsored by the National Cancer Institute, that were published in The New England Journal of Medicine. According to the FDA statement, 33 of 50 (66 percent) pediatric patients who received selumetinib through the SPRINT trial had partial tumor shrinkage, and 82 percent of these responses lasted at least 12 months. In addition, many of the children experienced reduced pain, which was one of the most common neurofibroma-related symptoms, along with disfigurement and motor dysfunction.

At the October 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, researchers reported preliminary results from a phase II study of selumetinib in adult NF1 patients who had plexiform neurofibromas. They found that 71 percent of 21 patients who could be evaluated had a partial response. In an AACR press release, the lead author of that study noted that the results are very exciting for adult patients suffering from the effects of plexiform neurofibromas, but that it is important to remember that they are preliminary.

The FDA approval was rendered on April 10, 2020.