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Nirogacestat

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Nirogacestat

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]

Quick Facts Clinical data, Trade names ...
Nirogacestat
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Clinical data
Trade namesOgsiveo
Other namesPF-03084014
AHFS/Drugs.comOgsiveo
License data
Routes of
administration		By mouth
Drug classGamma-secretase inhibitor
ATC code
Legal status
Legal status
Identifiers
  • (S)-2-((S)-5,7-Difluoro-1,2,3,4-tetrahydronaphthalen-3-ylamino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H41F2N5O
Molar mass489.656 g·mol−1
3D model (JSmol)
  • CCC[C@@](N[C@@]1([H])CCC2=CC(F)=CC(F)=C2C1)([H])/C(O)=N/C3=CN(C(C)(CNCC(C)(C)C)C)C=N3
  • InChI=1S/C27H41F2N5O/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35)/t20-,23-/m0/s1
  • Key:VFCRKLWBYMDAED-REWPJTCUSA-N
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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

Nirogacestat is indicated for adults with progressing desmoid tumors who require systemic treatment.[1][2]

History

Summarize
Perspective

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

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

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