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Nirogacestat is the first approved medicine for desmoid tumours, locally invasive growths that do not spread but can be crippling; it works by blocking Notch signalling.
Nirogacestat is an oral gamma-secretase inhibitor that prevents cleavage of Notch receptors and release of the Notch intracellular domain; desmoid tumours, driven by CTNNB1 or APC mutations, depend on crosstalk between Notch and Wnt signalling. In the phase 3 DeFi trial it reduced progression with a PFS HR of 0.29 versus placebo, produced objective responses in 41% versus 8%, and improved patient-reported pain and physical function (NEJM 2023). The FDA approved it on 27 November 2023 as the first systemic therapy for progressing desmoid tumours, and the EU followed in 2025. Diarrhoea is common, and ovarian toxicity affected 75% of women of childbearing potential, largely reversing on stopping. SpringWorks developed it and was acquired by Merck KGaA. Desmoid tumours never spread but can be crippling, and this is the first medicine proven to shrink them.
Inhibits gamma-secretase, preventing Notch receptor cleavage and NICD release; desmoid tumours (CTNNB1 or APC mutant) depend on Notch/Wnt crosstalk.
1.Nirogacestat binds the gamma-secretase complex
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. Progressing desmoid tumour requiring systemic therapy.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE search: nirogacestat. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2025-04-28 | SpringWorks Therapeutics (Merck KGaA) to Merck KGaA Nirogacestat (Ogsiveo) and mirdametinib (Gomekli) | Acquisition | not disclosed | $3.9bn | source |
Compare all products across the US, EU, UK, Japan, China and Australia →
First systemic therapy for desmoid tumours (DeFi) source
European Commission approval source
| Region | Year | Indication |
|---|---|---|
| US | 2023 | Progressing desmoid tumours requiring systemic treatment |
| EU | 2025 | Progressing desmoid tumours |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Diarrhoea DeFi | 84% | 16% |
| Ovarian toxicity women of childbearing potential; mostly resolved on stopping | 75% | - |
| Rash | 68% | - |
| Hypophosphataemia | 65% | - |
Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
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Query for this drug: (TITLE:"Nirogacestat" OR ABSTRACT:"Nirogacestat" OR TITLE:"Ogsiveo" OR ABSTRACT:"Ogsiveo") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Nirogacestat, not a curated reading list.
Shares Gamma-secretase (PSEN1), Notch signalling.
Shares Gamma-secretase (PSEN1), Notch signalling.
Shares Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM, Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple, Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants Wi, Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMM.
Shares CTNNB1, APC, Wnt / β-catenin.
Shares Gamma-secretase (PSEN1), Desmoid tumour.
Shares Intermittent or stop-and-restart nirogacestat in desmoid tumours, Wrong doses.
Shares SpringWorks Therapeutics (Merck KGaA), Merck KGaA (EMD Serono), Small-molecule kinase inhibitors.
Shares CTNNB1, APC, Wnt / β-catenin.