OnCo
drugsProductApproved2023🇪🇺🇬🇧

Nirogacestat

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.

DeFi: PFS HR 0.29 vs placebo; ORR 41% vs 8%; pain and physical function improved. Approved US 27 November 2023 (first systemic therapy for desmoid tumours); EU 2025. Ovarian toxicity (75% of women of childbearing potential, largely reversible) is the notable adverse effect. SpringWorks/Merck KGaA.

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Nirogacestat
PubChem
Mechanism, step by step
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1.Nirogacestat binds the gamma-secretase complex

Modality
Small-molecule gamma-secretase inhibitor
Mechanism
Inhibits gamma-secretase, preventing Notch receptor cleavage and NICD release; desmoid tumours (CTNNB1 or APC mutant) depend on Notch/Wnt crosstalk.
Brand / code
Ogsiveo
Dosing & schedule
Route
Oral
Schedule
150 mg twice daily continuously
Monitoring
Diarrhoea, ovarian function/hormones, phosphate, liver enzymes, skin, non-melanoma skin cancer
Medicare
Part D (self-administered)

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).

Commercial insurance
covered with prior authorisation

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.

Assistance programmes

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.

Not appraisedSearch NICE
Notes
EU-licensed 2025 for desmoid tumours; UK licence and NICE position not yet researched.
NHS England
Not routinely funded

Sources: NICE search: nirogacestat. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.

Regulatory

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  1. 27 Nov 2023ApprovalUS

    First systemic therapy for desmoid tumours (DeFi) source

  2. 2025ApprovalEU

    European Commission approval source

Approvals

RegionYearIndication
US2023Progressing desmoid tumours requiring systemic treatment
EU2025Progressing desmoid tumours

Safety

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Toxicity profile
Adverse eventAny gradeGrade 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.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Nirogacestat
intervention: Nirogacestat
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

Latest papers

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Literature trend20 papers in the last 12 months+25% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

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.

Connected

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