SpringWorks Therapeutics recently celebrated a landmark achievement with the FDA approval of Gomekli (mirdametinib) for neurofibromatosis type 1 (NF1), marking a triumph not just for the company but for a new collaborative model in rare disease drug development. The approval on February 11, 2023, represents the culmination of an extraordinary rescue mission for a drug once abandoned by pharmaceutical giant Pfizer.
Gomekli's journey from shelved asset to approved therapy offers a blueprint that advocates believe could revolutionize rare disease drug development across the industry.
The Rescue of a Promising Drug
Neurofibromatosis type 1 is a genetic disorder that causes benign tumors to grow along the nervous system, potentially leading to blindness, deafness, bone abnormalities, disfigurement, pain, and in some cases, cancer. Prior to Gomekli, adult patients had no FDA-approved treatment options.
The drug's path to approval began when the Children's Tumor Foundation (CTF), which had funded early preclinical work on mirdametinib, refused to accept Pfizer's decision to discontinue the promising compound. Despite showing clinical potential, Pfizer had shifted priorities toward other assets.
"I said, 'Guys, this drug is really doing something,'" recounted Annette Bakker, CEO of CTF, describing her conversations with Pfizer executives. Her persistence paid off when Pfizer's Laura Sullivan recognized the drug's potential and helped spin out SpringWorks Therapeutics in 2017 specifically to advance this and other shelved assets.
The biotech launched with a $103 million Series A funding round supported by Pfizer, Bain Capital Life Sciences, Bain Capital Double Impact, OrbiMed, and LifeArc. This collaborative model was explicitly designed to deliver both social and financial returns.
Clinical Success Against Significant Odds
The pivotal ReNeu trial demonstrated Gomekli's efficacy with an objective response rate of 41% in adults and 52% in children. The drug produced deep and durable tumor volume reductions, with 80% of adults and 90% of children achieving a confirmed response of at least 12 months. Half of the patients maintained their response at 24 months.
These impressive results came despite significant challenges, including the COVID-19 pandemic, which threatened to derail recruitment efforts. Once again, CTF proved invaluable by mobilizing its network to ensure trial enrollment continued.
"We couldn't have done this without CTF," acknowledged Jim Cassidy, SpringWorks' Chief Medical Officer.
A Model for Rescuing Shelved Assets
Industry experts believe Gomekli's development story represents a scalable model for addressing a widespread problem in pharmaceutical R&D: promising drug candidates abandoned not for scientific reasons but due to business priorities.
"What we're building now can actually be copied to every rare disease under the sun," said Bakker, who estimates that approximately 30 more drugs that could help neurofibromatosis patients are currently in limbo at various companies.
The financial opportunity is substantial as well. Gomekli is projected to generate approximately $760 million in revenue by 2030, demonstrating that these rescue missions can create viable commercial opportunities.
The Growing Problem of "Ghost Assets"
The issue of abandoned drug candidates extends beyond large pharmaceutical companies. Carl Schoellhammer, associate partner at consulting firm DeciBio, refers to these as "ghost assets" – compounds developed by smaller biotechs that never reach patients due to business failures rather than scientific shortcomings.
"You see that a lot of companies are restructuring these days, and I think we're going to have an even more pronounced wave of what I call shell drugs that actually will never see the patient. And for a rare disease, that is a problem," Bakker explained.
The situation is particularly acute for platform companies and in trending therapeutic areas like mRNA and cell therapy, where numerous assets may be deprioritized as companies narrow their focus or struggle to secure additional funding.
Solutions to Unlock Shelved Potential
Several approaches could help rescue more abandoned assets:
Patient Advocacy Leadership
CTF's role in Gomekli's development highlights how patient advocacy organizations can serve as catalysts, connecting promising assets with investors and development expertise.
"That's got to be a CTF-like organization," Cassidy emphasized, noting the unique position these groups have to influence pharmaceutical decision-makers.
Investment Structures
Bakker is working to create "almost like an investor club of people that are willing to sustain these companies to make sure that they make it to the finish line." Holding companies that acquire and advance discontinued assets represent another potential solution.
Policy Changes
Tax incentives for companies willing to develop shelved assets and FDA policy changes to prevent data loss when companies are acquired or dissolved could further facilitate these efforts.
SpringWorks' Expanding Success
Gomekli represents SpringWorks' second FDA approval, following Ogsiveo for desmoid tumors 18 months earlier. Both drugs originated from Pfizer's portfolio of discontinued assets, validating the company's model.
"This is a tried and tested way of developing drugs in those very small, rare indications," said Cassidy.
Building Infrastructure for Future Success
CTF is now developing infrastructure to help public and private institutions collaborate more efficiently on drug development. This includes a clinical trials consortium to facilitate the movement of drugs into clinical testing.
The foundation is also working with the FDA, Sanofi, and the Myhre Syndrome Foundation to explore clustering rare diseases by type, potentially broadening treatment opportunities across multiple conditions.
"Our approach is, let us build a prototype that actually can be expanded to other rare diseases," Bakker said. "So it's not just for NF."
As the confetti continues to fall on SpringWorks' website celebrating Gomekli's approval, the company and its partners are already looking ahead to how their collaborative model can unlock more "ghost drugs" from pharmaceutical storerooms – potentially transforming the landscape for rare disease treatment development.
