Nirogacestat
Gamma secretase inhibitor
Table of contents
**Updates**
We updated this drug summary on 29th of August 2024, removed 'Snippets at a glance', removed TLDR section, added simple definitions, and condensed longer paragraphs into summary points to improve readability.
What is nirogacestat used for?
Nirogacestat blocks the enzyme gamma secretase.
It treats desmoid tumours by slowing down or stopping growth of the tumours.
Desmoid tumour - A growth of cells that form in the body's tissues. The tumour does not spread like cancer, but it can grow back after being removed.
What is the mechanism of action of nirogacestat?
Tumour growth signals - Messages that tell abnormal cells to grow and spread in the body.
The Notch pathway - A communication system between cells that helps control how cells grow and develop.
What are the contraindications of nirogacestat?
Full prescribing documentation - A detailed guide for doctors and healthcare professionals that explains how to safely prescribe and use a medication.
Important nirogacestat prescribing safety information.
The action of nirogacestat on the notch pathway affects intestines, phosphate levels, and ovarian function.
So regular monitoring through blood tests and hormone checks are advised as they can help manage side effects early.
Phosphate levels - A blood test to show how much of the mineral phosphate is in the blood. Too little phosphate can cause weakness and bone problems, while too much can lead to itchy skin and joint pain.
Ovarian function - How well the ovaries work to release eggs and make female hormones.
Nirogacestat patient counselling advice.
Recommend maintaining a healthy lifestyle that includes staying well-hydrated, a balanced diet and adequate sleep.
Signs of dehydration - Include feeling thirsty, dry mouth, dark urine, dizziness, and feeling tired or weak.
References
References
1. Gounder, M.M., Ravin Ratan, Alcindor, T., Schöffski, P., Ta, Wilky, B.A., Riedel, R.F., Lim, A., L Mary Smith, Moody, S., Attia, S., Chawla, S.P., D’Amato, G.Z., Federman, N., Merriam, P., Van, B.A., Vincenzi, B., Benson, C., Bui, N.Q. and Chugh, R. (2023). Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors. The New England Journal of Medicine, 388(10), pp.898–912. doi:https://doi.org/10.1056/nejmoa2210140. Link
2. Loggers, E.T., Chugh, R., Federman, N., Hartner, L., Riedel, R.F., Cho, S., Hyslop, D., Lim, A., Oton, A.B. and Oktay, K.H. (2024). Onset and resolution of ovarian toxicity with nirogacestat treatment in females with desmoid tumors: Updated safety analyses from the DeFi phase 3 study. Cancer. doi:https://doi.org/10.1002/cncr.35324. Link
3. Messersmith, W.A., Shapiro, G.I., Cleary, J.M., Jimeno, A., Dasari, A., Huang, B., Shaik, N., Cesari, R., Zheng, X., Reynolds, J.L., English, P.A., McLachlan, K., Kern, K.A. and LoRusso, P. (2015). A Phase I, Dose-Finding Study in Patients with Advanced Solid Malignancies of the Oral γ-Secretase Inhibitor PF-03084014. 21(1), pp.60–67. doi:https://doi.org/10.1158/1078-0432.ccr-14-0607. Link
4. OGSIVEO® (nirogacestat) -. (2023). Desmoid Tumor Information, Resources, and Support - OGSIVEO® (nirogacestat). [online] Available at: https://www.ogsiveo.com [Accessed 29 Aug. 2024]. Link