Information below provided by the Pharmaceutical Company.

Nirogacestat (OGSIVEO™)

Agent Description

Nirogacestat is an oral gamma secretase inhibitor. Nirogacestat has the chemical name: (S)-2-(((S)-6,8-Difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide dihydrobromide. It has a molecular formula of C₂₇H₄₃Br₂F₂N₅O and the molecular weight is 651.48 g/mol.

Mechanism of Action

Nirogacestat is a gamma secretase inhibitor that blocks proteolytic activation of the Notch receptor. When dysregulated, Notch can activate pathways that contribute to tumor growth.

Classification

Gamma Secretase Inhibitor

Molecular Target

Gamma secretase

Monograph

Nirogacestat is indicated for adult patients with progressing desmoid tumors who require systemic treatment.

Ongoing studies in desmoid tumors: Open-label extension of a Phase 3 study in adult patients with progressing desmoid tumors/aggressive fibromatosis (NCT03785964) and Phase 2 study investigating nirogacestat in pediatric desmoid tumor patients conducted in collaboration with Children's Oncology Group (NCT04195399).

Ongoing studies of other tumors: Phase 2 study of nirogacestat as monotherapy in recurrent ovarian granulosa cell tumors (NCT05348356).

In addition, nirogacestat is being evaluated for patients with multiple myeloma as part of several BCMA combination therapy regimens in collaboration with industry partners.

Package insert: https://springworkstx.com/wp-content/uploads/2023/11/OGSIVEO-US-Prescribing-Information-11.27.23.pdf

Studies of Interest

Areas of Interest:

• Exploration of nirogacestat as monotherapy or rational combinations with other therapies in preclinical models and/or in the clinic in disease indications that are supported by scientific rationale.

Information collaborator would like included in investigator proposals

N/A