Nirogacestat
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| Trade names | Ogsiveo |
| Other names | PF-03084014 |
| AHFS/Drugs.com | Ogsiveo |
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| Routes of administration | By mouth |
| Drug class | Gamma-secretase inhibitor |
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| Formula | C27H41F2N5O |
| Molar mass | 489.656 g·mol−1 |
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Nirogacestat, sold under the brand name Ogsiveo, is an anti-cancer medication used for the treatment of desmoid tumors.[1][2][3] It is a selective gamma secretase inhibitor[4] that is taken by mouth.[1]
The most common side effects include diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea.[2][3]
Nirogacestat was approved for medical use in the United States in November 2023.[2] It is the first medication approved by the US Food and Drug Administration (FDA) for the treatment of desmoid tumors.[2][5] The FDA considers it to be a first-in-class medication.[6]
Medical uses
[edit]Nirogacestat is indicated for adults with progressing desmoid tumors who require systemic treatment.[1][2]
History
[edit]The effectiveness of nirogacestat was evaluated in DeFi (NCT03785964), an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial in 142 adult participants with progressing desmoid tumors not amenable to surgery.[3] Participants were randomized to receive 150 milligrams (mg) of nirogacestat or placebo orally, twice daily, until disease progression or unacceptable toxicity.[2] The main efficacy outcome measure was progression-free survival (the length of time after the start of treatment for which a person is alive and their cancer does not grow or spread).[2] Objective response rate (a measure of tumor shrinkage) was an additional efficacy outcome measure.[2] The pivotal clinical trial demonstrated that nirogacestat provided clinically meaningful and statistically significant improvement in progression-free survival compared to placebo.[2] Additionally, the objective response rate was also statistically different between the two arms with a response rate of 41% in the nirogacestat arm and 8% in the placebo arm.[2] The progression-free survival results were also supported by an assessment of patient-reported pain favoring the nirogacestat arm.[2]
As of 2021, nirogacestat was in phase II clinical trials for unresectable desmoid tumors.[7][needs update] In addition, a phase III clinical trial, DeFi, was in progress for nirogacestat for adults with desmoid tumors and aggressive fibromatosis.[8] In addition, three trials were recruiting patients that include nirogacestat with other anticancer therapies in multiple myeloma, including the UNIVERSAL study for nirogacestat with the allogeneic CAR-T therapy ALLO-715.[9][10][11]
The FDA granted the application for nirogacestat priority review, fast track, breakthrough therapy, and orphan drug designations.[2][3] The FDA granted the approval of Ogsiveo to SpringWorks Therapeutics Inc.[2]
Society and culture
[edit]Legal status
[edit]Nirogacestat was granted breakthrough therapy designation by the FDA in September 2019, for adults with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.[12]
References
[edit]- ^ a b c d "Ogsiveo- nirogacestat tablet, film coated". DailyMed. 8 December 2023. Archived from the original on 12 December 2023. Retrieved 12 December 2023.
- ^ a b c d e f g h i j k l m "FDA Approves First Therapy for Rare Type of Non-Cancerous Tumors". U.S. Food and Drug Administration (FDA) (Press release). 27 November 2023. Archived from the original on 28 November 2023. Retrieved 28 November 2023.
This article incorporates text from this source, which is in the public domain.
- ^ a b c d "FDA approves nirogacestat for desmoid tumors". U.S. Food and Drug Administration (FDA). 27 November 2023. Archived from the original on 30 November 2023. Retrieved 30 November 2023. This article incorporates text from this source, which is in the public domain.
- ^ Chen X, Chen X, Zhou Z, Mao Y, Wang Y, Ma Z, et al. (September 2019). "Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-Induced bone resorption in vivo". Experimental Cell Research. 382 (1): 111470. doi:10.1016/j.yexcr.2019.06.015. PMID 31211955. S2CID 195065514.
- ^ "SpringWorks Therapeutics Announces FDA Approval of Ogsiveo (nirogacestat) as the First and Only Treatment for Adults with Desmoid Tumors" (Press release). SpringWorks Therapeutics. 27 November 2023. Archived from the original on 28 November 2023. Retrieved 28 November 2023 – via GlobeNewswire.
- ^ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
- ^ Clinical trial number NCT04195399 for "A Safety, Pharmacokinetic and Efficacy Study of a y-Secretase Inhibitor, Nirogacestat (PF-03084014) in Children and Adolescents With Progressive, Surgically Unresectable Desmoid Tumors" at ClinicalTrials.gov
- ^ Clinical trial number NCT03785964 for "A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF)" at ClinicalTrials.gov
- ^ Clinical trial number NCT04093596 for "A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy With or Without Nirogacestat in Subjects With Relapsed/Refractory Multiple Myeloma" at ClinicalTrials.gov
- ^ Clinical trial number NCT04722146 for "A Multi-arm Phase 1b Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma" at ClinicalTrials.gov
- ^ Clinical trial number NCT04126200 for "A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) - DREAMM 5" at ClinicalTrials.gov
- ^ "FDA Grants Nirogacestat Breakthrough Designation for Desmoid Tumors". OncLive. 4 September 2019. Archived from the original on 25 June 2021. Retrieved 25 June 2021.
