A genetic disease that causes tumors to form on nerves has a new FDA-approved treatment, a SpringWorks Therapeutics drug that can address a wider range of patients than the AstraZeneca product that was first to treat this rare disorder.
The disease, neurofibromatosis type 1 (NF1), is technically not cancer as the tumors that form are benign. But NF1 can lead to cancers. Even if a patient’s tumors aren’t cancerous, they are painful and disfiguring. The FDA approval announced Tuesday covers the treatment of NF1 tumors that cannot be surgically removed. The drug, known in development as mirdametinib, will be marketed under the brand name Gomekli. SpringWorks expects the new product will become available within two weeks.
Stamford, Connecticut-based SpringWorks estimates 100,000 people have NF1 globally; about 40,000 of these patients are in the U.S. The disease stems from mutations in the NF1 gene, which codes for a protein key to suppressing MAPK, a pathway that, when hyperactivated, drives cancer growth. Tumors that result from the mutations are usually aggressive, growing rapidly during a patient’s childhood. Surgery is the first treatment option, but the location of tumors at or near vital structures or organs can make this choice risky. Off-label drug options include cancer medications, such as chemotherapy and immunotherapy.
Gomekli is an oral small molecule designed to block MEK1 and MEK2, two proteins that play key roles in the MAPK pathway. MEK inhibitors have already been approved for treating certain cancers. Koselugo, the AstraZeneca drug that became the first FDA approved NF1 therapy in 2020, is a MEK inhibitor that was initially tested in various solid tumors. In NF1, Koselugo is approved only for treating pediatric patients age 2 and older. The SpringWorks drug has an advantage with an approval that covers the treatment of adults as well as children.
The FDA decision for Gomekli was based on the results of a single-arm, Phase 2 study that enrolled 114 patients — 58 adults and 56 children — with symptomatic, inoperable NF1-associated tumors. The main goal was to measure for the disappearance or reduction of tumors. Results showed the overall response rate was 41% for adults and 52% for children. The most common adverse reactions included rash, diarrhea, nausea, and muscle pain.
The study results were published this past November in the Journal of Clinical Oncology. Dr. Christopher Moertel, medical director pediatric neuro-oncology and neurofibromatosis programs at the University of Minnesota and the lead investigator of the ReNeu clinical trial, said NF1 patients face significant health challenges and have limited treatment options.
“It was very encouraging in the ReNeu trial to see that Gomekli provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy,” Moertel said in SpringWorks’ announcement. “This approval represents an important advance, especially for adults who previously did not have an approved treatment.”
Gomekli is available as a capsule as well as a tablet that may be swallowed or mixed in water. The twice-daily drug is available in two dosage strengths. Precise dosing is determined by a patient’s body surface area, taking into account both height and weight. SpringWorks set a wholesale price of $206.25 per mg, according to a Wednesday regulatory filing. The company estimates the average cost of treatment will be about $22,000 per month for pediatric patients and $30,000 per month for adults.
The Gomekli approval comes as SpringWorks has emerged as a potential acquisition target for Merck KGaA. Following a Reuters report of negotiations for a deal, the German company issued a statement Monday confirming advanced discussions with SpringWorks. However, Merck KGaA said the companies have not entered a legally binding agreement, adding that “critical conditions have yet to be met.”
If Merck KGaA can swing a deal for SpringWorks, it will get more than the new NF1 drug. In 2023, SpringWorks drug Ogsiveo received the FDA nod for treating desmoid tumors, a rare type of tumor affecting connective tissue. For the nine months ended Sept. 30, 2024, Ogsiveo accounted for $110 million in revenue, according to the biotech’s most recent financial report. Both Ogsiveo and Gomekli were initially developed by Pfizer, which spun them off into standalone company SpringWorks in 2017.
Beyond NF1, SpringWorks is testing Gomekli in certain cancers. As a monotherapy, the drug has reached mid-stage clinical testing in pediatric low-grade gliomas. Under a partnership with BeiGene, Gomekli is also being tested in solid tumors driven by RAS and RAF mutations; a Phase 1 study is evaluating the SpringWorks drug in combination with BeiGene’s experimental lifirafenib, a small molecule inhibitor of RAF enzymes.
Photo by SpringWorks Therapeutics
