Nirogacestat

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.

• OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment.

• None. None.contraindicated

The recommended dosage is 150 mg orally twice daily until disease progression or unacceptable toxicity. ( 2.1 ) See Full Prescribing Information for dosage modifications due to adverse reactions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of OGSIVEO is 150 mg administered orally twice daily until disease progression or unacceptable toxicity. OGSIVEO may be taken with or without food. Instruct patients to swallow OGSIVEO tablets whole and not to break, crush, or chew prior to swallowing. If a patient vomits or misses a dose, instruct the patient to take the next dose at its scheduled time. 2.2 Dos ag e Modifications for Adverse Reactions The recommended dose modifications for OGSIVEO for selected severe adverse reactions are summarized in Table 1 [ see Warnings and Precautions ( 5 ) , Adverse Reactions ( 6 ) ]. For other severe adverse reactions, life-threatening adverse reactions, or persistent intolerable Grade 2 adverse reactions, withhold drug until resolved to Grade ≤ 1 or baseline. Only restart at a dosage of 100 mg twice daily after considering the potential benefit and likelihood of recurrence of the adverse reaction. Permanently discontinue OGSIVEO for recurrence of severe or life-threatening adverse reaction upon rechallenge at the reduced dose. Table 1.

Diarrhea : Severe diarrhea can occur. Monitor and dose modify for Grade 3-4 diarrhea. ( 5.1 ) Ovarian Toxicity : Female reproductive function and fertility may be impaired. Advise females of reproductive potential of the potential risk prior to treatment and monitor routinely. ( 5.2 ) Hepatotoxicity : Elevated AST and ALT can occur. Monitor AST and ALT regularly and modify dose as recommended. ( 5.3 ) Non-Melanoma Skin Cancers : Perform dermatologic examination prior to initiation of OGSIVEO and routinely during treatment. ( 5.4 ) Electrolyte Abnormalities : Monitor phosphate and potassium regularly and modify dose as recommended. ( 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Diarrhea Diarrhea, sometimes severe, can occur in patients treated with OGSIVEO [see Adverse Reactions ( 6.1 ) ] . In DeFi, diarrhea occurred in 84% of patients treated with OGSIVEO, and included Grade 3 events in 16% of patients. Median time to first diarrhea event for patients treated with OGSIVEO was 9 days (range: 2 to 434 days). Monitor patients and manage using antidiarrheal medications. Modify dose as recommended [ see Dosage and Administration ( 2.2 ) ]. 5. 2 Ovarian Toxicity Female reproductive function and fertility may be impaired in patients being treated with OGSIVEO. Impact on fertility may depend on factors including the duration of therapy and the state of gonadal function at the time of treatment.

The following serious adverse reactions are described elsewhere in the labeling: Diarrhea [ see Warnings and Precautions ( 5.1 )] Ovarian Toxicity [ see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Non-Melanoma Skin Cancers [see Warnings and Precautions ( 5.4 )] Electrolyte Abnormalities [ see Warnings and Precautions ( 5.5 )] The most common ( > 15 %) adverse reactions are diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea. ( 6.1 ) The most common laboratory abnormalities (≥15%) are decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SpringWorks Therapeutics at 1-888-400-7989 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OGSIVEO was evaluated in 69 patients enrolled in DeFi with progressing desmoid tumor [see Clinical Studies ( 14 ) ]. Patients received OGSIVEO 150 mg orally twice daily or placebo orally twice daily until disease progression or unacceptable toxicity. The median duration of exposure to OGSIVEO was 20.6 months (range: 0.3 to 33.6).

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, OGSIVEO can cause fetal harm or loss of pregnancy when administered to a pregnant woman [ see C linical Pharmacology ( 12.1 ) ] . Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity and embryo-fetal death at maternal exposures below the human exposure at the recommended dose of 150 mg twice daily [see Data ] . There are no available data on the use of OGSIVEO in pregnant women. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Daily oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in decreased fetal body weights, pre- and post-implantation loss, and fetal subcutis edema at doses ≥ 20 mg/kg/day (approximately 0.85 times the recommended dose of 150 mg twice daily based on area under the curve). 8.2 Lactation Risk Summary There are no data on the presence of nirogacestat or its metabolites in human milk or the effects of nirogacestat on a breastfed child or milk production.

Metabolism

Nirogacestat pharmacokinetic parameters in patients with desmoid tumors are summarized in Table 6 . Table 6.

Due to the high level of protein binding, OGSIVEO is not expected to be dialyzable [see Clinical Pharmacology ( 12.3 )] .

• Nov 27, 2023NDANDA217677Springworks

1. 1Diarrhoea29337%
2. 2Nausea18423%
3. 3Fatigue15319%
4. 4Rash10313%
5. 5Headache8110%
6. 6Product Dose Omission Issue769.6%
7. 7Vomiting729.1%
8. 8Stomatitis577.2%
9. 9Cough455.7%
10. 10Intentional Underdose415.2%
11. 11Alopecia405.1%
12. 12Product Dose Omission In Error394.9%
13. 13Pruritus394.9%
14. 14Abdominal Discomfort374.7%
15. 15Epistaxis354.4%

The 10 most recently updated of 32 ClinicalTrials.gov registrations naming Nirogacestat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma
  Active not recruiting · Phase 1 · Interventional · 140 enrolled · Janssen Research & Development, LLC
  NCT04722146updated 2026-06-05
• Nirogacestat in Patients With Kaposi Sarcoma
  Not yet recruiting · Phase 2 · Interventional · 28 enrolled · AIDS Malignancy Consortium
  NCT07539454updated 2026-05-28
• Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study
  Recruiting · Phase 2 · Interventional · 40 enrolled · M.D. Anderson Cancer Center
  NCT05879146updated 2026-05-15
• Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)
  Completed · Phase 1 · Interventional · 73 enrolled · Allogene Therapeutics
  NCT04093596updated 2026-05-13
• A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)
  Active not recruiting · Phase 2 · Interventional · 20 enrolled · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT07170644updated 2026-05-08
• Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)
  Recruiting · Phase 4 · Interventional · 50 enrolled · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT07176689updated 2026-05-08
• Individual Patient Compassionate Use of Nirogacestat
  Available · Expanded access · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT05041036updated 2026-05-08
• Evaluate the Effects of Famotidine or Rabeprazole on the PK of Nirogacestat
  Completed · Phase 1 · Interventional · 24 enrolled · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT07171619updated 2026-05-08
• Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 208 enrolled · GlaxoSmithKline
  NCT04126200updated 2026-05-06
• Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 106 enrolled · GlaxoSmithKline
  NCT07084896updated 2026-05-06

Frequently asked questions

How does Nirogacestat work?

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.

What is Nirogacestat used for?

According to FDA labeling, Nirogacestat carries indications including: OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nirogacestat?

Nirogacestat is classified as Other antineoplastic agents, Gamma Secretase Inhibitor, Cytochrome P450 2C19 Inducers, Cytochrome P450 3A Inhibitors, Gamma Secretase Inhibitors, Protease Inhibitors, Cellular Activity Alteration.

What are the brand names for Nirogacestat?

Nirogacestat is marketed under brand names including Ogsiveo.

What are the contraindications for Nirogacestat?

Nirogacestat labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.