FDA approves drug for neurofibromatosis

The US Food and Drug Administration has approved mirdametinib for the treatment of neurofibromatosis type 1 (NF1) in adults and children. The drug, developed by SpringWorks Therapeutics, is the first approved for treatment of NF1 in children and adults. It will be marketed under the name Gomekli.

Neurofibromatosis is a rare genetic condition in which tumors grow on Schwann cells, which act as insulation to protect nerve cells. “The Schwann cells are like your white plastic around your electric wires, and as soon as these cells touch, they stop proliferating,” explains Annette Bakker, a pharmacologist and CEO of the Children’s Tumor Foundation, a patient research nonprofit focused on NF1. But in people with NF1, once those cells touch, they don’t stop proliferating “and you get these tumors that are formed on the nerves,” Bakker says. NF1 is not explicitly a form of cancer, but she does call it a “cancer predisposition syndrome.”

Mirdametinib treats NF by acting on the RAS signaling pathway involved in cell growth and differentiation. It inhibits mitogen-activated protein kinase enzymes, which when overactive are implicated in many cancers. When patients with NF1 take the drug, their tumors shrink by “50–60%,” Bakker says.

The drug is a remarkable example of successful drug repositioning, in which drugs that have gone through Phase 1 clinical trials but are not approved continue to be explored, often for a new use, Bakker says. Pfizer had shelved the drug after it appeared that AstraZeneca would beat it to market with a competing drug. But mirdametinib still held value to the NF1 community, so the Children’s Tumor Foundation lobbied Pfizer for access to the drug, which was then spun off to SpringWorks for further research.

Bakker hopes that more pharmaceutical companies will consider drug repositioning as a means to get lifesaving medication on the market. “What we need to do as a community is to think very carefully about a business model that incentivizes companies to let these drugs go,” she says. “Because for the moment, it's still very dependent on goodwill.”