Ogsiveo Receives FDA Approval as First Therapy for Desmoid Tumors

Pfizer spinout SpringWorks Therapeutics’ Ogsiveo (nirogacestat) has received US Food and Drug Administration (FDA) approval for the treatment of desmoid tumors, an ultra-rare subtype of non-cancerous soft tissue sarcomas that can cause severe pain and disfigurement.

Ogsiveo is indicated for adult patients with progressing desmoid tumors who require systemic treatment.

Ogsiveo is the first approved drug for desmoid tumors and SpringWorks’ first approved commercial product. The company spun out of Pfizer in 2017 with a portfolio of rare disease products.

Desmoid tumors are also known as aggressive fibromatosis or desmoid-type fibromatosis (as they arise from fibroblasts). Despite being benign, the locally aggressive and invasive soft-tissue tumors can cause debilitating pain, problems with movement and can even be life-threatening if they affect vital structures and organs.

While desmoid tumors do not metastasize, they are difficult to treat. They are often refractory to current off-label systemic therapies, with recurrence rates of up to 77 percent following surgical resection. Treatment guidelines now recommend systemic therapies as first-line interventions instead of surgery for most tumor cases.

The incidence of desmoid tumors is three to five individuals per million every year. In the US, SpringWorks estimates that 1,000 to 1,650 new cases of desmoid tumor could be diagnosed per year. Currently, approximately 6,000 to 7,000 Americans are receiving treatment for the disease and more than 20,000 patients are not for reasons that include concerns about treatment side effects.

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“Our team is honored to deliver the first FDA-approved therapy for patients with desmoid tumors. This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” said Saqib Islam, CEO of SpringWorks, in a news release from SpringWorks announcing the approval.

He said, “We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe Ogsiveo has the potential to become the new standard of care for people living with these devastating tumors.”

Ogsiveo is an oral, selective, small molecule gamma-secretase inhibitor that was first developed for Alzheimer’s disease and then breast cancer.

National Cancer Institute (NCI) researcher Shivaani Kummar, MD, who was leading a breast cancer trial for the drug saw its potential in desmoid tumor based on early phase trial data, leading to the spinning off of SpringWorks from Pfizer to further develop it.

Ogsiveo’s FDA approval was based on efficacy data from the multicenter, randomized, placebo-controlled Phase III DeFi trial in 142 adult patients with progressing desmoid tumors not suitable for surgery. Seventy seven percent of participants in the trial had received previous treatment. Ogsiveo led to a 71 percent reduction in the risk of disease progression or death compared to placebo.

Ogsiveo also demonstrated significant improvements in pain and other disease-related measurements compared to placebo. The drug was associated with a higher rate of side effects including diarrhea, nausea, sore mouth and rash, which prompted reducing the dose for 42 percent of patients in the trial.

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SpringWorks said it is also evaluating nirogacestat as a potential treatment for ovarian granulosa cell tumors (a rare subtype of ovarian cancer) and multiple myeloma as part of several B-cell maturation agent (BCMA) combination therapy regimens.

As an inhibitor of gamma secretase, Ogsiveo can prevent cleavage of BCMA receptors on the surface of tumor cells, which can increase BCMA target density for drugs. In particular, BCMA has been found to have selective and higher expression on plasma cells over normal cells in multiple myeloma, making it an attractive drug target.

SpringWorks is exploring Ogsiveo as a BCMA-targeting agent in combination treatments, including with GSK’s antibody-drug conjugate Blenrep (belantamab mafodotin-blmf), Johnson & Johnson’s T-cell engager Tecvayli (teclistamab-cqyv) and Pfizer’s bispecific Elrexfio (elranatamab-bcmm).

Ogsiveo was granted FDA Breakthrough Therapy, Fast Track and Orphan Drug designations for the treatment of desmoid tumors.

SpringWorks said Ogsiveo will be available to order through a specialty pharmacy and specialty distributor network in the US within five to ten business days. The Connecticut-based company also said it plans to file a Marketing Authorisation Application for Ogsiveo in desmoid tumors with the European Medicines Agency (EMA) in the first half of 2024.

SpringWorks revealed that the drug will have a list price of $29,000 for a one-month supply.

Ogsiveo was evaluated under the FDA’s Real-Time Oncology Review (RTOR) pathway, which allows for data submission and regulatory review at the same time.