SpringWorks Therapeutics sprung out of Pfizer’s storeroom, when a rare disease advocacy group pushed to keep a program for neurofibromatosis alive. This method could work for “every rare disease under the sun,” advocates say.
Every drug approval is a monumental occasion worthy of celebration. But for SpringWorks Therapeutics, the approval of rare disease medicine Gomekli is doubly exhilarating. So much so, that a burst of confetti greets visitors to the company’s website right now.
That’s because Gomekli, known as mirdametinib up until February 11 when it was approved to treat patients with neurofibromatosis type 1 (NF), defied greater odds than most drugs. Once discontinued by Pfizer and banished to gather dust in the pharma’s intellectual property attic, the drug was rescued by the nonprofit patient advocacy group Children’s Tumor Foundation, who convinced executives to give it new life.
Gomekli’s development is the story of everything going right, with the right people throwing everything they had into getting it approved so that patients with the rare tumor disorder could finally have a real treatment option. And it’s one that executives, advocates and consultants say could be repeated over and over again, applied to “every rare disease under the sun.”
“We couldn’t have done this without CTF,” Jim Cassidy, SpringWorks’ chief medical officer, told BioSpace.
A New Way to Get Things Done
Thirteen years ago, after a career that included long stints at Johnson & Johnson, Annette Bakker went to the nonprofit sector. Frustrated with the slow pace of drug development, Bakker wanted to help fix the massive chasm between academia and industry. Academic institutions were churning out excellent science and models, while the industry had hugely promising drugs. But without a clear line between the two, progress was stalled and drug failures were all too common.
“There is one main opportunity that I saw is that there is a lot of companies that are actually not developing drugs. Not because they’re not good drugs and not because they can’t be effective for patients; they are just being discontinued for commercial, marketing, strategic opportunities, and that is what pharmaceutical companies do,” Bakker said in an interview.
She and CTF felt that a nonprofit could help facilitate the relationships, help bring patients for specific diseases to the companies. CTF, where Bakker is CEO, focuses on the genetic disease NF, which causes benign tumors to grow along the nervous system. The condition can lead to blindness, deafness, bone abnormalities, disfigurement, pain or even cancer. The tumors are not always easy to resect, leaving medication as the only option. Adults have never had an approved treatment option, according to Cassidy.
CTF had funded early preclinical work on mirdametinib before Pfizer took it up, pushing the drug all the way to initial clinical evidence in a small population before cutting it. This caused a “furor” at CTF, according to Cassidy, as the drug had begun to show great promise. The organization was not ready to give up, even if Pfizer’s priorities had changed.
Bakker went to Pfizer’s Laura Sullivan. “I said, ‘Guys, this drug is really doing something.’” But Pfizer explained that the company was bowing to selumetinib, a drug developed by Alexion, now part of AstraZeneca. It was eventually approved in April 2020 and is marketed as Koselugo, but only for pediatric patients. Adults were still left without an option.
Sullivan evidently thought mirdametinib had something too. She spun out with the drug and became president of SpringWorks. She’s now the CEO of Pyxis Oncology, another Pfizer spinout.
“Pfizer [was] open to the idea of essentially farming this out, spinning out something to develop this drug, even though they didn’t want to develop it any further,” Cassidy said. “And that’s where SpringWorks come into it.”
Bakker said that about 200 people were involved in getting the drug out of Pfizer. “I always say it was a story of believers,” she said. “We need believers. We need to find champions in the company that say I’m in because this requires, still, a lot of volunteer work.”
The biotech was launched in September 2017, described as a way to advance investigational therapies for underserved patients. The company’s “collaborative business model is designed to deliver both social and financial returns,” in partnership with scientists, biopharma partners, patient groups, funders and philanthropists, according to a release announcing the launch. Pfizer supported the $103 million series A, which also included Bain Capital Life Sciences, Bain Capital Double Impact, OrbiMed and LifeArc.
“SpringWorks Therapeutics started as an idea about a new way to get things done with—and for—patients,” said Pfizer’s then CMO Freda Lewis-Hall. The company initially had four assets for four diseases, including NF, desmoid tumors, hereditary xerocytosis and post-traumatic stress disorder. Mirdametinib was one of them.
“It was really kind of being able to present a great package to the investors, to the people that needed to put their money and their resources into this asset,” Bakker explained. This required volunteers from Pfizer, to whom Bakker is grateful.
CTF didn’t lose interest when SpringWorks took over, either. Bakker says the group has been involved throughout the drug development process, helping SpringWorks plan a Phase IIb trial, find sites and investigators.
“That, in itself, is a huge lift for us, and we were a very small, very young company at the time. Whether we’d ever been able to do that on our own is an open question,” Cassidy said.
The study was just getting underway as COVID-19 hit. As the entire world essentially shut down, so did a lot of clinical research across the industry. SpringWorks suddenly saw a huge dent in recruitment efforts for the mirdametinib trial and they knew exactly where to turn. CTF rallied its advocates—“beat the bushes,” according to Cassidy—to drum up interest and get patients enrolled.
When the results came in for the mid-stage ReNeu trial, mirdametinib spurred improvements in pain and quality of life. Specifically, the drug led to an objective response rate of 41% in adults and 52% in children. The drug showed deep and durable tumor volume reductions of 41% in adults and 42% in children, with 80% of adults and 90% of children achieving a confirmed response of at least 12 months. Half of patients still had a response at 24 months.
These data ultimately underpinned the FDA approval, which SpringWorks received on February 11.
This is SpringWorks’ second rare disease drug approval, after Ogsiveo, which was approved 18 months ago for desmoid tumors. Cassidy said it was also from the batch of Pfizer assets, and while it didn’t take quite the same advocacy path as Gomekli, it was a discontinued asset at one point.
Cassidy said it’s time to share with others how this process worked so effectively to get a rare disease drug approved. “This is a tried and tested way of developing drugs in those very small, rare indications.”
Editor’s note: The following story is part one in a two part story looking at discontinued assets in biopharma. You can read Part Two, How to Mine BioPharma’s IP Storeroom for Rare Disease Drugs, Just Like SpringWorks, here.
