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The Desmoid Tumor Research Foundation

DTRF Press Release: 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 (More)

SpringWorks

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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

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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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*Update: Watch the 2022 DTRF Annual Patient Meeting presentations on the Nirogacestat results and the AL102 results. For all Patient Meeting recordings, visit Patient Meeting.*

BIG NEWS this Desmoid Tumor Awareness Month!

Presentations on the latest data from two promising clinical trials – both studying gamma secretase inhibitor drugs in desmoid tumors – were given this past weekend at the 2022 European Society for Medical Oncology (ESMO) conference in Paris, France.

PLEASE NOTE: Presentations tailored for the patient community on these two trials and their data will be given at the Annual Patient Meeting Webinar #2 (of 3) on Sept. 24th during the DTRF Together We Will Virtual Weekend. Register at no cost at DTRF.org/weekend, and bring your questions!

Both of these presentations have left us encouraged and hopeful. The interest in desmoid tumor research is higher than ever before and we are making significant progress in finding more effective and more manageable therapies. If you have fundraised for or donated to the DTRF, you have helped make this progress possible by supporting our patient outreach, advocacy, research, awareness, and scientific collaboration efforts. Give today.

Here are the details from the ESMO presentations:

  • NIROGACESTAT – Phase 3 DeFi Clinical Trial (SPRINGWORKS THERAPEUTICS)

On Saturday, Principal Investigator Bernd Kasper, MD, (University of Heidelberg, Maneheim) presented the latest data from the SpringWorks Therapeutics Phase 3 DeFi clinical trial for nirogacestat (a gamma secretase inhibitor) in desmoid tumor patients during the Presidential Symposium session of ESMO.

“Results showed a statistically significant improvement in progression-free survival in patients randomised to nirogacestat compared to the placebo group, with a 71% lower risk of disease progression on average. The response rate was also much higher – 41% in the nirogacestat arm and only 8% in the placebo arm; nearly one in ten patients (7%) showed a complete response with the agent.” 

– Bernd Kasper, MD, PhD, University of Heidelberg, Principal Investigator of the DeFi trial

For more information, see the SpringWorks’ press release

…and the ESMO article.

  • AL102 – RINGSIDE Phase 2/3 Clinical Trial (AYALA PHARMACEUTICALS)

On Monday, Prof. Robin Jones, MD, (The Royal Marsden) presented the latest data from the Ayala Pharmaceuticals RINGSIDE Phase 2/3 clinical trial for AL102 (a gamma secretase inhibitor) in desmoid tumor patients.

“Efficacy was demonstrated across all cohorts of Part A of the study, with early responses that deepened over time. The results also showed that AL102 was well-tolerated across all doses.” 

– Roni Mamluk, PhD, CEO of Ayala


For more information, read Ayala’s press release

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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.