BioPharma, Pharma

FDA Approval of SpringWorks Drug Is the First for Rare Connective Tissue Tumor

SpringWorks Therapeutics drug Ogsiveo is now FDA-approved for treating desmoid tumors, a type of tumor affecting connective tissue. The regulatory decision makes the pill the first therapy approved specifically for treating this rare disorder.

A SpringWorks Therapeutics drug has won FDA approval for treating a rare connective tissue tumor, making it the first approved therapy for this type of tumor. It’s also the first product approval for the Pfizer spinout.

Desmoid tumors are soft tissue tumors that develop in connective tissue. They’re related to cancers of connective tissue called sarcomas, but are not considered cancerous because they do not spread throughout the body. However, desmoid tumors can be locally aggressive, invading surrounding healthy tissues such as joints, muscle, and internal organs. The resulting tumor growth can cause chronic pain, disfigurement, internal bleeding, and impaired range of motion.

While desmoid tumors can be removed surgically, recurrence of these tumors is high. Cancer drugs and opioids can be used as off-label treatments, but these medicines have limited efficacy and introduce a wide range of side effects, SpringWorks CEO Saqib Islam said, speaking during a Tuesday conference call.

“All of these are the alternatives that people use that actually are false choices from our perspective, and there’s a reason that nothing else is approved because nothing else works for an extended period of time,” Islam said.

FDA approval of the Stamford, Connecticut-based company’s new drug covers the treatment of patients whose desmoid tumors are not suitable for surgical removal. The twice daily pill, known in development as nirogacestat, will be marketed under the brand name Ogsiveo.

Ogsiveo is a small molecule designed to block an enzyme called gamma secretase, which in turn has the effect of blocking activation of the Notch receptor. Dysregulation of this receptor contributes to tumor growth. FDA approval of Ogsiveo is based on results of a placebo-controlled study that enrolled 142 adults with progressing desmoid tumors not amenable to surgery. The main goal was to measure progression-free survival, defined as the length of time the patient is alive after the start of treatment until the tumors progress. The study also assessed tumor shrinkage.

Results showed clinically meaningful and statistically significant improvement in progression-free survival in the treatment arm compared to the placebo group. A patient-reported pain assessment also favored the study drug. The most common side effects reported in the trial included diarrhea, ovarian toxicity, rash, nausea, fatigue, inflammation in the mouth called stomatitis, headache, and abdominal pain.

Ogsiveo came from Pfizer, which had advanced the drug as far as Phase 1 testing. In 2017, the pharmaceutical giant bundled Ogsiveo with another drug candidate that no longer fit with its pipeline plans, spinning out those assets into new company SpringWorks.

The former Pfizer asset may yet find use as a cancer drug. Through partnerships with big pharma companies, including Pfizer, the SpringWorks molecule is being evaluated as part of combinations with approved multiple myeloma medicines that target the cancer protein BCMA. The basic idea is that blocking gamma secretase may improve the activity of BCMA-targeting drugs. But SpringWorks’ internal research with its lead molecule remains focused on rare tumors. The company is testing whether its gamma secretase inhibitor can also treat ovarian granulosa cell tumors, a type of ovarian cancer. A Phase 2 test is ongoing.

The other SpringWorks drug candidate licensed from Pfizer is mirdametinib, a potential treatment for neurofibromatosis type 1-associated pexiform neurofibromas, or NF1-PN. This disease causes a rare type of tumor to develop on the peripheral nerve sheath. Mirdametinib is designed to block the MEK pathway. While MEK inhibitors are already available as cancer treatments, these drugs aren’t well tolerated by patients. SpringWorks aims to block MEK while offering a tolerability profile that enables long-term use of the drug. Two weeks ago, SpringWorks reported positive preliminary Phase 2b data. Based on those results, Islam said the company plans to file an FDA submission for mirdametinib in the first half of 2024.

In the nearer term, SpringWorks is preparing for Ogsiveo’s launch. The company estimates that 1,600 patients are newly diagnosed with desmoid tumors in the U.S. annually, and between 5,500 and 7,000 patients are actively managing the condition. SpringWorks Chief Commercial Officer Bhavesh Ashar said Ogsiveo will become available within the next 10 business days. The company has set a wholesale price of $29,000 for a 30-day supply of the drug. SpringWorks is also eyeing other markets for its new drug. Islam said the company plans to file a European Union application for Ogsiveo in the first half of next year.

Per terms of the license agreement, SpringWorks owes Pfizer up to $232.5 million in milestone payments tied to commercialization of Ogsiveo. Pfizer will also receive royalties from sales of the new product.

Photo: SpringWorks Therapeutics