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The Desmoid Tumor Research Foundation

FDA APPROVES OGSIVEO™ (NIROGACESTAT), AS THE FIRST MEDICAL THERAPY FOR THE TREATMENT OF ADULTS WITH PROGRESSING DESMOID TUMORS.

OGSIVEO FDA-Approval Featured Image

Gamma-secretase inhibitor

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(Pittsburgh, PA) – November 27, 2023 – The U.S. Food and Drug Administration (FDA) announced approval today of OGSIVEO (nirogacestat) for the treatment of adults with progressing desmoid tumors. This is the first FDA-approved medical therapy in this rare disease. FDA approval follows positive results from the SpringWorks Therapeutics, Inc. (Nasdaq: SWTX) DeFi (NCT03785964) phase 3 clinical trial, a global, randomized, double-blind, placebo-controlled trial evaluating nirogacestat in adult patients with desmoid tumors. Results from the DeFi trial were published on March 9, 2023, in The New England Journal of Medicine in the article, “Nirogacesat, a γ-Secretase Inhibitor for Desmoid Tumors,” by Drs. Gounder, Ratan, Kummar, Kasper et al.

OGSIVEO (nirogacestat) is an oral gamma secretase inhibitor. For more information, visit www.ogsiveo.com.

“The significance of FDA approval of OGSIVEO (nirogacestat) to desmoid tumor patients cannot be overstated. This is an extraordinary victory in the area of rare diseases, and demonstrates the power of collaboration among patients, industry and researchers.”

Jeanne Whiting, Executive Director Emeritus, Desmoid Tumor Research Foundation

“SpringWorks is grateful to the Desmoid Tumor Research Foundation, as well as the patients and investigators who participated in our trials, whose enduring commitment and enthusiasm helped us get to this point. We are honored to provide the first FDA-approved therapy and committed to offering ongoing support to the desmoid tumor community throughout their treatment journey on OGSIVEO.”

Saqib Islam, Chief Executive Officer, SpringWorks Therapeutics

The collaborative path to approval

The Desmoid Tumor Research Foundation (DTRF) has been instrumental in the nearly 15-year path to approval of OGSIVEO (nirogacestat). The drug was first studied in patients with a range of solid tumors including seven desmoid tumor patients. A poster presentation of the promising results of this early work in desmoid tumors caught the eye of members of the National Cancer Institute’s (NCI) Rare Tumors Initiative, Shivaani Kummar, MD and Abby Sandler, PhD. The pair were interested in a phase 2 trial, but due to the rare nature of the disease, concluded that in order to be successful they needed the support of a patient advocacy organization. Synergistic collaboration between the DTRF and NCI brought the phase 2 trial forward, and with the DTRF’s outreach efforts, filled it in less than five months. 

Despite promising results that were coming out of the phase 2 study, a business decision resulted in halting the development of the asset. Determined not to let this potential treatment stall, the DTRF once again galvanized its resources and continued discussions with Pfizer staff. Supportive clinicians, as well as encouraging staff at Pfizer, supported the effort to move the drug forward. Eventually SpringWorks Therapeutics was created to license nirogacestat and other assets that showed potential in underserved patient populations.

Under newly-formed SpringWorks, the phase 3 DeFi trial for nirogacestat opened. During the conduct of the DeFi trial, and with the help of DTRF’s patient outreach, the trial was fully enrolled in July 2020. In September 2022, trial data were presented in a Presidential Symposium during the ESMO Congress and at the annual DTRF International Desmoid Tumor Research Workshop. In December 2022, SpringWorks filed a New Drug Application for nirogacestat which was accepted for Priority Review on February 27, 2023. Today, FDA approval of OGSIVEO (nirogacestat), makes it the first FDA-approved drug for the treatment of adults with desmoid tumors.

“This breakthrough represents the power of patient advocacy. The Desmoid Tumor Research Foundation’s role in OGSIVEO’s path to approval represents collaboration at its finest. Were it not for their advocacy work to shepherd the drug through the trial phases, facilitate communication among stakeholders, and use their outreach to help fill the trial, we may not be here today. I’m honored to be part of the process that brings the first-ever FDA-approved medical therapy to desmoid tumor patients.”

Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center

About desmoid tumors

Desmoid tumors (also known as aggressive fibromatosis) are rare, invasive, soft tissue tumors that form in the connective tissues of the body. They affect 5-6 per 1 million people per year. Although they do not metastasize, desmoid tumors can be locally aggressive and severely damage surrounding tissues and vital structures as they grow. They are highly recurrent and can be multifocal. These tumors may occur anywhere in the body (abdominal, intraabdominal, and extra-abdominal locations) and approximately 5-10% arise in the context of a rare genetic condition known as Familial Adenomatous Polyposis (F.A.P.). Previously, there have been no approved therapies for desmoid tumors.

About The Desmoid Tumor Research Foundation

The Desmoid Tumor Research Foundation (DTRF) was co-founded in 2005 by Jeanne Whiting and Marlene Portnoy, with the mission of facilitating and funding desmoid tumor research and supporting patients with information. The DTRF’s mission is to aggressively fund research to accelerate the development of improved therapies, and ultimately find a cure for desmoid tumors. The DTRF collaborates with dedicated researchers and clinicians worldwide to facilitate research and improve the lives of patients through education, awareness and support. Every year the foundation’s progress has gained momentum with new clinical trials, emerging therapies and important new discoveries about the disease coming to fruition. The DTRF is a recipient of the National Organization of Rare Disorders Abby S. Meyers Leadership Rare Impact Award, and the Global Genes’ Champions of Hope Rare Champion in Advocacy Award. For more information, please visit www.DTRF.org.

For more information about this important milestone for desmoid tumor patients, read the FDA’s and SpringWorks’ press releases linked below.

SpringWorks Therapeutics Press Release

U.S. FDA Press Release

DTRF Press Release PDF

Media Inquiries

Maggie Cameron
Communications Manager, DTRF
Maggie@DTRF.org

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The Desmoid Tumor Research Foundation Announces That Groundbreaking Results From The Phase 3 Springworks Defi Trial Were Published Today In The New England Journal Of Medicine In The Article, “Nirogacestat, A Γ-Secretase Inhibitor For Desmoid Tumors.” The Fda Recently Accepted The New Drug Application (Nda) For Nirogacestat And It Is Now Under Priority Review.

(Pittsburgh, PA) – Thursday, March 9th, 2023 – Years of advocacy by The Desmoid Tumor Research Foundation (DTRF) facilitated clinical trials in nirogacestat in desmoid tumors. On February 27, 2023, SpringWorks Therapeutics announced FDA acceptance and Priority Review of their New Drug Application (NDA) for nirogacestat, for the treatment of adults with desmoid tumors. The NDA is based on the previously announced positive results from the DeFi (NCT03785964) phase 3 trial, a global, randomized, double-blind, placebo-controlled trial evaluating nirogacestat in adult patients with desmoid tumors. Results from the DeFi trial were published today in The New England Journal of Medicine in the article, “Nirogacesat, a γ-Secretase Inhibitor for Desmoid Tumors,” by Drs. Gounder, Ratan, Kummar, Kasper et al.

This exciting news follows a 14 year, arduous path. Nirogacestat, a γ-secretase inhibitor, was first studied in patients with a range of solid tumors including seven desmoid tumor patients. A poster presentation of the promising results of this work in desmoid tumors caught the eye of a member of the National Cancer Institute’s (NCI) Rare Tumors Initiative. The NCI team, Shivaani Kummar, MD and Abby Sandler, PhD, wanted to run a phase 2 trial, but due to the rare nature of the disease, concluded that they couldn’t be successful without the support of a patient advocacy organization. After they found the DTRF, NCI and the DTRF enthusiastically collaborated to bring the phase 2 trial forward. While it had been anticipated that it might take up to two years to fill this trial, with the DTRF’s outreach to patients, the trial was filled in less than 5 months.

Despite promising results that were coming out of the phase 2 study, a business decision resulted in halting the development of this molecule. Once again, the DTRF galvanized its resources and continued discussions with Pfizer staff, determined not to let this potential treatment stall because it showed such promise for desmoid tumor patients who have limited treatment options and no approved therapies. Supportive clinicians, as well as encouraging staff at Pfizer, supported the effort to move the drug forward. Eventually SpringWorks Therapeutics was created to acquire nirogacestat and other assets that showed potential in underserved patient populations. 

Under newly-formed SpringWorks, the phase 3 DeFi trial for nirogacestat eventually opened. Over the following 15 months, with the help of the DTRF’s outreach, the trial was fully enrolled. In September 2022, final trial data were presented in a Presidential Symposium during the ESMO Congress and at the DTRF’s annual International Desmoid Tumor Research Workshop. In December 2022, SpringWorks filed a New Drug Application for nirogacestat in desmoid tumors which was accepted for Priority Review on February 27, 2023. If approved, nirogacestat could be available to patients as the first FDA-approved therapy in desmoid tumors.

With the support of the DTRF, three additional clinical trials on desmoid tumors are currently underway. For a rare disease with an incidence rate of 5-6 per million, these are remarkable accomplishments that demonstrate the power of collaboration between patient groups, researchers and industry.

About The Desmoid Tumor Research Foundation 

The Desmoid Tumor Research Foundation (DTRF) was co-founded in 2005 by Jeanne Whiting and Marlene Portnoy, with the mission of facilitating and funding desmoid tumor research and supporting patients with information. The DTRF’s mission is to aggressively fund research to accelerate the development of improved therapies, and ultimately find a cure for desmoid tumors. The DTRF collaborates with dedicated researchers and clinicians worldwide to facilitate research and improve the lives of patients through education, awareness and support. Every year the Foundation’s progress has gained momentum with new clinical trials, emerging therapies and important new discoveries about the disease coming to fruition. The DTRF is the recipient of the National Organization of Rare Disorders Abby S. Meyers Leadership Rare Impact Award, and the Global Genes’ Champions of Hope Rare Champion in Advocacy Award. For more information, please visit www.dtrf.org.

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Press Contact:
Maggie Cameron
Communications Manager, DTRF
Maggie@DTRF.org

Download PDF

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SpringWorks Therapeutics has announced FDA acceptance and priority review of the New Drug Application (NDA) for nirogacestat, their investigational gamma secretase inhibitor for the treatment of adults with desmoid tumors.

“The acceptance of our NDA for nirogacestat with Priority Review represents a significant milestone in our ambition to provide the first approved therapy for patients with desmoid tumors. We look forward to working closely with the FDA during the review process and remain focused on ensuring that we are well-positioned to expeditiously serve the desmoid tumor patient and the physician communities following approval.”

Saqib Islam, CEO, SpringWorks Therapeutics

Read the press release

What This Means

This announcement brings our community one step closer to an FDA-approved therapy for desmoid tumors. The FDA now has until August 27, 2023 to complete the review process, which will lead to a decision of whether nirogacestat will receive FDA approval. This is very exciting!

Related News

The DeFi phase 3 trial results that lead to this NDA were published in The New England Journal of Medicine. The publication and NDA are remarkable accomplishments that demonstrate the power of collaboration between patient groups, researchers and industry.

Read DTRF Press Release.
Read “Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors” on NEJM.org.

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SpringWorks Therapeutics has announced that it has submitted a New Drug Application to the U.S. FDA for nirogacestat, their investigational gamma secretase inhibitor for the treatment of adults with desmoid tumors. 

“Our NDA submission represents an important step toward potentially delivering the first approved therapy for patients with desmoid tumors.” 

– Saqib Islam, CEO, SpringWorks Therapeutics 

Read the press release

What Happens Next 

Once submitted, the FDA has about 60 days to decide whether to “accept” the New Drug Application (NDA). If accepted, the official FDA review process will start. 

A standard FDA review process is typically about 10 months. SpringWorks has applied for various regulatory designations that the FDA has in place to review drugs that treat serious conditions and fulfill an unmet need. The FDA granted nirogacestat Fast-Track and Breakthrough Therapy Designations in the past, and SpringWorks also plans to submit the NDA for review under the FDA’s Real-Time Oncology Review program. 

All of this is good news and means that there is recognition that there is an important need for a new drug like nirogacestat.

Because there are many variables with the FDA approval process, SpringWorks is only able to say right now that it expects the FDA to make a decision sometime in 2023. As more precise timelines become available, SpringWorks will let the DTRF know, and we will then be able to update our community.

To learn more about the nirogacestat Phase 3 clinical trial results, please watch the recording of Dr. Ravin Ratan’s (MD Anderson Cancer Center) presentation from the 2022 DTRF Annual Patient Meeting in September. 

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On May 24, 2022, SpringWorks Therapeutics announced topline results from their Phase 3, double-blind, placebo-controlled trial called the DeFi trial. This trial evaluates the gamma secretase inhibitor, nirogacestat, for efficacy, safety and tolerability in adult patients with progressing desmoid tumors.

The DeFi trial’s primary endpoint was met by improving progression-free survival (PFS) for usage of nirogacestat compared to placebo, with a 71% reduction in the risk of desmoid tumor progression.

SpringWorks Therapeutics expects to present additional data at an upcoming medical conference as well as submit a New Drug Application (NDA) to the U.S. Food and Drug Administration in the second half of 2022.

From SpringWorks Therapeutics’ press release:

“‘Desmoid tumors are aggressive soft-tissue tumors that can lead to severe negative outcomes for patients, including long-lasting pain, disfigurement, and amputation. In rare cases, when vital organs are impacted, desmoid tumors can also be life-threatening,’ said Saqib Islam, Chief Executive Officer of SpringWorks. ‘Today’s announcement represents a significant milestone towards our goal of bringing the first approved therapy to the desmoid tumor community. We look forward to sharing the DeFi trial data with the FDA and to presenting detailed study results at a medical meeting later this year.’”

The DTRF would like to express our gratitude to members of the community who have participated in and are currently enrolled in clinical trials, including the DeFi trial. Your participation is advancing our understanding of desmoid tumors and bringing us closer to improved treatments for all desmoid tumor patients.