– Nirogacestat Treatment Resulted in Rapid, Sustained and Statistically Significant Improvements in Primary and All Key Secondary Efficacy Endpoints –
– NDA Submission to the U.S. FDA Planned for Second Half of 2022; Application to be Submitted for Review Under the FDA’s Real-Time Oncology Review Program (RTOR) –
– Company to Host Virtual Investor Event on Sunday, September 11 at 10:00 a.m. ET (4:00 p.m. CEST) –
STAMFORD, Conn., Sept. 10, 2022 (GLOBE NEWSWIRE) — SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical firm centered on growing life-changing medicines for sufferers with extreme uncommon ailments and most cancers, introduced that information from the Phase 3 DeFi trial of nirogacestat, an investigational oral gamma secretase inhibitor, in grownup sufferers with progressing desmoid tumors, are being offered in the present day as a late-breaking oral presentation throughout a Presidential Symposium on the European Society for Medical Oncology (ESMO) Congress 2022.
“Desmoid tumors can have a debilitating impact on patients’ lives and there is an urgent need for a new standard-of-care treatment,” stated Saqib Islam, Chief Executive Officer of SpringWorks. “DeFi is the largest and most robust Phase 3 trial conducted to date in patients with desmoid tumors and we believe these positive data bring us a step closer toward potentially introducing the first approved therapy for this underserved community. We look forward to completing our full NDA filing package by the end of the year, which will be submitted for review under FDA’s RTOR program.”
The DeFi trial met its major endpoint of bettering progression-free survival (PFS), as assessed by blinded impartial central evaluation, demonstrating a statistically vital enchancment for nirogacestat over placebo, with a 71% discount within the danger of illness development (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). The median Kaplan-Meier estimate of PFS was not reached within the nirogacestat arm and was 15.1 months within the placebo arm. A PFS profit was noticed throughout all prespecified subgroups, together with gender, tumor location, prior therapy or surgical procedure, and mutational standing. Confirmed goal response price (full response + partial response) primarily based on RECIST v1.1 was 41% with nirogacestat versus 8% with placebo (p<0.001). The full response price was 7% within the nirogacestat arm and 0% within the placebo arm. Nirogacestat demonstrated statistically vital and clinically significant enhancements in patient-reported outcomes (PRO), which had been key secondary endpoints of the research. Specifically, nirogacestat considerably lowered ache (p<0.001) and different DT-specific signs (p<0.001) and likewise considerably improved bodily/position functioning (p<0.001) and total health-related high quality of life (p=0.007). Most PRO advantages had been noticed as early as Cycle 2, which was the primary timepoint for post-treatment analysis, and had been sustained over the length of the research.
At the time of major evaluation (April 7, 2022), the median length of therapy was 20.6 months for contributors on nirogacestat and 11.4 months for these on placebo, with nearly all of nirogacestat sufferers persevering with on therapy. Nirogacestat exhibited a manageable security profile within the DeFi trial, with 95% of all treatment-emergent antagonistic occasions (TEAEs) reported as Grade 1 or 2. The most steadily reported TEAEs in contributors receiving nirogacestat as in comparison with the placebo arm had been diarrhea (84% vs 35%), nausea (54% vs 39%), and fatigue (51% vs 36%). Forty-two p.c of sufferers within the nirogacestat arm vs 0% within the placebo arm required dose reductions attributable to TEAEs and 20% of sufferers within the nirogacestat arm vs 1% within the placebo arm discontinued therapy attributable to TEAEs. Ovarian dysfunction, which was outlined by investigator-reported occasions of amenorrhea, untimely menopause, menopause, and ovarian failure, was noticed in 75% (27/36) of girls of childbearing potential receiving nirogacestat. These occasions resolved in 74% (20/27) of the affected contributors, together with 64% (9/14) of such contributors who remained on nirogacestat therapy and 100% (11/11) of these contributors who discontinued therapy for any cause.
“The DeFi study enrolled patients with progressing desmoid tumors at baseline and included a high proportion of patients with multifocal disease and uncontrolled pain, representing a very difficult-to-treat patient population,” stated Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial. “The consistently positive data generated across progression-free survival, objective response rate, and patient-reported outcomes, coupled with a safety profile that is suitable for long-term dosing, support the potential for nirogacestat to become an important and much needed treatment for patients with desmoid tumors.”
ESMO Oral Presentation Details
Title: DeFi: A Phase 3, Randomized Controlled Trial of Nirogacestat Versus Placebo for Progressing Desmoid Tumors (DT)
Presentation Number: LBA2
Presenter: Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany
Session/Type: Presidential Symposium 1, Proffered Paper Session
Date: Saturday, September 10, 2022
Time: 4:55-5:10 p.m. CEST (10:55-11:10 a.m. ET)
Investor Event Details
Presenters: SpringWorks’ administration group will probably be joined by Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial.
Date: Sunday, September 11, 2022
Time: 4:00 p.m. CEST (10:00 a.m. ET)
Instructions: To be a part of the reside webcast and think about corresponding slides, please go to the Events & Presentations web page throughout the Investors & Media part of the Company’s web site at https://ir.springworkstx.com. To be a part of through audio teleconference, please register right here. Once registration is full, contributors will probably be supplied with a dial-in quantity and convention code to entry the decision. A replay will probably be obtainable on the Company’s web site for a restricted time following the occasion.
About the DeFi Trial
DeFi (NCT03785964) is a worldwide, randomized (1:1), double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, security and tolerability of nirogacestat in grownup sufferers with progressing desmoid tumors. The double-blind part of the research randomized 142 sufferers (nirogacestat, n=70; placebo n=72) to obtain 150 mg of nirogacestat or placebo twice day by day. Key eligibility standards included tumor development by >20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) inside 12 months previous to the primary dose of research therapy. The major endpoint is progression-free survival, as assessed by blinded impartial central evaluation. Secondary and exploratory endpoints embody security and tolerability measures, goal response price (ORR), length of response, adjustments in tumor quantity assessed by magnetic resonance imaging (MRI), and adjustments in patient-reported outcomes (PROs). DeFi consists of an open label extension part, which is ongoing.
About Desmoid Tumors
Desmoid tumors are uncommon, aggressive, domestically invasive, and probably morbid tumors of the gentle tissues.1,2 While they don’t metastasize, desmoid tumors are related to a excessive price of recurrence.2,3,4 Sometimes known as aggressive fibromatosis, or desmoid fibromatosis, these gentle tissue tumors will be severe, debilitating, and, in uncommon circumstances when very important buildings are impacted, they are often life-threatening.2,5
Desmoid tumors are mostly identified in sufferers between the ages of 20 and 44 years, with a two-to-three instances increased prevalence in females.4,6,7,8 It is estimated that there are 1,000-1,650 new circumstances identified per 12 months within the United States.7,8,9
Historically, desmoid tumors had been handled with surgical resection, however this strategy has turn into much less favored attributable to a excessive recurrence price after surgical procedure.1,4,10 There are presently no FDA-approved therapies for the therapy of desmoid tumors.
About Nirogacestat
Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 scientific growth for desmoid tumors, that are uncommon and sometimes debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves a number of transmembrane protein complexes, together with Notch, which is believed to play a task in activating pathways that contribute to desmoid tumor progress.
In addition, gamma secretase has been proven to immediately cleave membrane-bound B cell maturation antigen (BCMA), ensuing within the launch of the BCMA extracellular area (ECD) from the cell floor. By inhibiting gamma secretase, membrane-bound BCMA will be preserved, rising goal density whereas lowering ranges of soluble BCMA ECD, which can function decoy receptors for BCMA-directed therapies. Nirogacestat’s skill to reinforce the exercise of BCMA-directed therapies has been noticed in preclinical fashions of a number of myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has eight collaborations with industry-leading BCMA builders to guage nirogacestat in mixtures throughout modalities, together with with an antibody-drug conjugate, two CAR T cell therapies, three bispecific antibodies and a monoclonal antibody. SpringWorks has additionally shaped analysis collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to additional characterize the flexibility of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies utilizing a wide range of preclinical a number of myeloma fashions.
Nirogacestat has obtained Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the therapy of desmoid tumors and from the European Commission for the therapy of sentimental tissue sarcoma. The FDA additionally granted Fast Track and Breakthrough Therapy Designations for the therapy of grownup sufferers with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. SpringWorks plans to submit a New Drug Application (NDA) to the FDA within the second half of 2022, which will probably be submitted for evaluation below the FDA’s Real-Time Oncology Review (RTOR) program.
About SpringWorks Therapeutics
SpringWorks is a clinical-stage biopharmaceutical firm making use of a precision medication strategy to buying, growing and commercializing life-changing medicines for sufferers residing with extreme uncommon ailments and most cancers. SpringWorks has a differentiated focused oncology pipeline spanning stable tumors and hematological cancers, together with two probably registrational scientific trials in uncommon tumor varieties in addition to a number of applications addressing extremely prevalent, genetically outlined cancers. SpringWorks’ strategic strategy and operational excellence in scientific growth have enabled it to quickly advance its two lead product candidates into late-stage scientific trials whereas concurrently coming into into a number of shared-value partnerships with innovators in {industry} and academia to unlock the total potential for its portfolio and create extra options for sufferers with most cancers. For extra data, go to www.springworkstx.com and comply with @SpringWorksTx on Twitter and LinkedIn.
SpringWorks Forward-Looking Statements
This press launch incorporates “forward-looking statements” throughout the which means of the Private Securities Litigation Reform Act of 1995, as amended, regarding our business, operations, and monetary circumstances, together with, however not restricted to, present beliefs, expectations and assumptions relating to the way forward for our business, future plans and techniques, our growth plans, our preclinical and scientific outcomes, the potential for nirogacestat to turn into an essential new therapy for sufferers with desmoid tumors, the potential for the outcomes of the Phase 3 DeFi scientific trial to assist an NDA submission, the timing of our deliberate NDA submission for nirogacestat, and our plans for looking for regulatory approval for and making nirogacestat obtainable to desmoid tumor sufferers, if authorised, in addition to regarding different future circumstances. Words reminiscent of, however not restricted to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and related expressions or phrases, determine forward-looking statements. New dangers and uncertainties could emerge from time to time, and it’s not attainable to foretell all dangers and uncertainties. Any forward-looking statements on this press launch are primarily based on administration’s present expectations and beliefs and are topic to quite a lot of dangers, uncertainties and essential components that will trigger precise occasions or outcomes to vary materially from these expressed or implied by any forward-looking statements contained on this press launch, together with, with out limitation, dangers regarding: (i) the success and timing of our product growth actions, together with the initiation and completion of SpringWorks’ scientific trials, (ii) our expectations relating to the potential scientific profit to sufferers with desmoid tumors primarily based upon the outcomes of our DeFi trial, (iii) the truth that topline or interim information from a scientific research might not be predictive of the ultimate or extra detailed outcomes of such research, or the outcomes of different ongoing or future research, (iv) the success and timing of our collaboration companions’ ongoing and deliberate scientific trials, (v) the timing of our deliberate regulatory submissions and interactions, together with the NDA for nirogacestat deliberate for the second half of 2022 and the timing and final result of selections made by the U.S. Food and Drug Administration (FDA) and different regulatory authorities, investigational evaluation boards at scientific trial websites and publication evaluation our bodies; (vi) whether or not FDA or different regulatory authorities would require extra data or additional research, or could fail or refuse to approve or could delay approval of our drug candidates, together with nirogacestat and mirdametinib, (vii) our skill to acquire and preserve regulatory approval of any of our product candidates, (viii) our plans to analysis, uncover and develop extra product candidates, (ix) our skill to enter into collaborations for the event of latest product candidates, (x) our skill to determine manufacturing capabilities, and our and our collaboration companions’ skills to fabricate our product candidates and scale manufacturing, (xi) our skill to fulfill any particular milestones set forth herein, and (xii) uncertainties and assumptions relating to the affect of the COVID-19 pandemic on SpringWorks’ business, operations, scientific trials, provide chain, technique, objectives and anticipated timelines.
Except as required by relevant regulation, we don’t plan to publicly replace or revise any forward-looking statements contained herein, whether or not because of any new data, future occasions, modified circumstances or in any other case. Although we imagine the expectations mirrored in such forward-looking statements are affordable, we may give no assurance that such expectations will show to be appropriate. Accordingly, readers are cautioned to not place undue reliance on these forward-looking statements.
For additional data relating to the dangers, uncertainties and different components that will trigger variations between SpringWorks’ expectations and precise outcomes, it’s best to evaluation the “Risk Factors” in Item 1A of Part I of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, in addition to discussions of potential dangers, uncertainties and different essential components in SpringWorks’ subsequent filings.
Contacts:
Kim Diamond
Vice President, Communications and Investor Relations
Phone: 203-561-1646
Email: [email protected]
Samantha Hilson Sandler
Director, Investor Relations
Phone: 203-461-5501
Email: [email protected]
References
1 Kasper B, Baumgarten C, Garcia J, et al; Desmoid Working Group. An replace on the administration of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Ann Oncol. 2017;28(10):2399-2408.
2 Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, administration and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274.
3 Xie Y, Xie Okay, Gou Q, He J, Zhong L, Wang Y. Recurrent desmoid tumor of the mediastinum: a case report. Oncol Lett. 2014;8(5):2276-2278.
4 Skubitz KM. Biology and therapy of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964.
5 Joglekar SB, Rose PS, Sim F, Okuno S, Petersen I. Current views on desmoid tumors: the Mayo Clinic strategy. Cancers (Basel). 2011;3(3):3143-3155.
6 Penel N, Coindre JM, Bonvalot S, et al. Management of desmoid tumours: a nationwide survey of labelled reference centre networks in France. Eur J Cancer. 2016;58:90-96.
7 van Broekhoven DLM, Grünhagen DJ, den Bakker MA, van Dalen T, Verhoef C. Time traits within the incidence and therapy of extra-abdominal and stomach aggressive fibromatosis: a population-based research. Ann Surg Oncol. 2015;22(9):2817-2823.
8 Anneberg M, Svane H, Fryzek J, et al. The Epidemiology of Desmoid Tumors in Denmark. Cancer Epidemiology. 2022; 77:1-7. doi.org/10.1016/j.canep.2022.102114.
9 Orphanet Report Series: Rare Diseases assortment. Prevalence and incidence of uncommon ailments: bibliographic information. Number 1, January 2022. Accessed April 28, 2022. https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf.
10 The Desmoid Tumor Working Group. The administration of desmoid tumors: a joint world evidence-based consensus guideline strategy for grownup and pediatric sufferers. Accessed April 10, 2022. https://dtrf.org/wp-content/uploads/2020/02/Desmoid_Paper_2018_A4_RL_Web300-1.pdf.
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