April 10, 2020 will forever be a significant milestone for the NF community. On this day, the FDA approved the first drug that was ever developed for neurofibromatosis type 1 (NF1). Selumetinib (aka AstraZeneca’s Koselugo) has been approved to treat symptomatic and inoperative NF1-associated plexiform neurofibromas and is currently in the midst of clinical trials to evaluate the possible benefits to other NF1-associated tumors.
The development of an NF1 therapy didn’t just happen overnight. “The selumetinib approval is the culmination of more than a decade of efforts in the NF community,” said Michael Fisher, MD, Chief of Neuro-Oncology and Director of the Neurofibromatosis Program at the Children’s Hospital of Philadelphia and a member of the Gilbert Family Foundation’s Vision Restoration Initiative (VRI) ‘Dream Team.’ Dr. Fisher was actively involved in the early phases of the selumetinib clinical trials.
“It required the development of mouse models of plexiform, the establishment of an NF Clinical Trials Consortium, a collaborative spirit between the lab researchers and the clinical researchers, the establishment of REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) which helped define the endpoints for clinical trials, and the partnership from sponsors such as the Department of Defense NF Research Program, Children’s Tumor Foundation and the Neurofibromatosis Therapeutic Acceleration Program.”
Drug development in general is lengthy and costly, so adding disease-specific research tools and involvement of specialists and stakeholders are critical components of the process. “The development of selumetinib is a shining example of true translational medicine,” said Roger Packer, MD, Senior Vice President of the Center for Neuroscience and Behavioral Medicine, Director of both the Gilbert Neurofibromatosis Institute and Brain Tumor Institute at Children’s National Hospital, and also a member of VRI. “Taking a molecular-targeted agent from the laboratory to a well-conceived and focused clinical trial to drug approval in less than a decade.” Dr. Packer and his team were also involved with clinical testing of this new therapy.
Despite the fact that selumetinib has been approved for plexiform neurofibromas, researchers and clinicians are still actively working towards improving outcomes for patients who use it. “For children with plexiform neurofibromas, there remain multiple important questions concerning selumetinib use,” said Dr. Packer, “including how long the drug should be utilized, if the drug coupled with other molecular-targeted agents will result in longer disease control and even better outcomes, and whether early use of the drug prevents the development of malignant nerve sheath tumors.” Understanding the answers to these questions are necessary to incorporate selumetinib effectively into patient treatment plans.
The FDA approval of this therapy will also expand its accessibility for patients who may benefit from its use. “These therapies will no longer be limited to selected large NF1 academic centers, but will, in the near future, be available to children across the United States and hopefully, soon, across the world. For many, this means less suffering and an improved quality of life, and it also opens the door for even more therapies to be available in the near future for other manifestations of NF1,” says Dr. Packer.
As of today, Selumetinib is also being evaluated in clinical trials for other NF1-associated tumors, including optic pathway and other low-grade gliomas, cutaneous neurofibromas, and malignant peripheral nerve sheath tumors.
The Gilbert Family Foundation is honored to have dedicated scientists like Drs. Fisher and Packer on our team to support the development of new therapies to treat NF1. “To have a medication specifically approved from an NF1 indication is the first step in changing the landscape for our patients and families,” states Dr. Fisher. While the first FDA-approved NF1 therapy is a momentous milestone for the NF1 community, selumetinib only helps a fraction of the approximately 3 million NF1 patients around the world. We are just getting started.