Ogsiveo: Uses, Dosage & Side Effects
An oral gamma-secretase inhibitor for adults with progressing desmoid tumors requiring systemic treatment
Ogsiveo (nirogacestat) is a prescription oral targeted therapy used to treat adults with progressing desmoid tumors who require systemic therapy. It is the first medication to receive regulatory approval specifically for desmoid tumors, a rare type of soft-tissue growth that can cause severe pain, functional impairment, and disability despite being classified as non-metastatic. Nirogacestat is a small-molecule gamma-secretase inhibitor that interferes with Notch signaling, a pathway frequently dysregulated in desmoid tumors through mutations in the CTNNB1 or APC genes. The medication is taken as three 50 mg tablets twice daily (total daily dose 300 mg). In the pivotal phase 3 DeFi trial, Ogsiveo reduced the risk of disease progression or death by 71% compared with placebo and produced measurable tumor shrinkage in 41% of treated patients, along with clinically meaningful improvements in pain and physical function.
Quick Facts: Ogsiveo
Key Takeaways
- Ogsiveo (nirogacestat) is the first medication specifically approved for adults with progressing desmoid tumors requiring systemic therapy, addressing a long-standing unmet need in the treatment of this rare, locally aggressive soft-tissue tumor.
- It works by selectively inhibiting gamma-secretase, thereby blocking the Notch signaling pathway and reducing the activity of the Wnt/beta-catenin pathway that drives desmoid tumor cell proliferation.
- The recommended dose is three 50 mg tablets taken orally twice daily (300 mg total per day), approximately 12 hours apart, with or without food, and continued until disease progression or unacceptable toxicity.
- In the phase 3 DeFi trial, Ogsiveo reduced the risk of progression or death by 71% versus placebo, produced a 41% objective response rate (versus 8% for placebo), and significantly improved pain, physical functioning, and overall quality of life.
- The most important safety concerns are ovarian toxicity in females of reproductive potential, diarrhea, hepatotoxicity, hypophosphatemia, and embryo-fetal toxicity; strong and moderate CYP3A inhibitors, CYP3A inducers, and P-glycoprotein inhibitors must be avoided during treatment.
What Is Ogsiveo and What Is It Used For?
Ogsiveo contains the active substance nirogacestat, a small-molecule, selective, oral inhibitor of gamma-secretase. Gamma-secretase is a multi-protein intramembrane protease complex that cleaves numerous substrates, most notably Notch receptors. By blocking this cleavage, nirogacestat suppresses the downstream Notch signaling activity that contributes to the aberrant growth behavior observed in desmoid tumor cells. Nirogacestat is developed and marketed by SpringWorks Therapeutics and was granted approval by the U.S. Food and Drug Administration (FDA) on 27 November 2023 under the brand name Ogsiveo, making it the first and only therapy approved with a specific indication for desmoid tumors.
Desmoid tumors, also known as desmoid-type fibromatosis or aggressive fibromatosis, are rare monoclonal soft-tissue proliferations of fibroblasts and myofibroblasts. Although they do not metastasize and are not classified as cancer in the strict histological sense, they can behave aggressively locally, infiltrating surrounding muscles, fascia, nerves, blood vessels, and visceral structures. The result is often severe pain, functional impairment, cosmetic disfigurement, and in some cases life-threatening complications when the tumor involves critical anatomy such as the mesentery, bowel, major vessels, or spinal structures. Desmoid tumors affect an estimated 5 to 6 individuals per million per year, with a strong predominance in adults between 30 and 40 years of age and a higher incidence in women, particularly in association with pregnancy or abdominal surgery.
At the molecular level, the vast majority of sporadic desmoid tumors harbor activating mutations in the CTNNB1 gene, which encodes beta-catenin, a central effector of the Wnt signaling pathway. Approximately 5% to 15% of patients have desmoid tumors in the context of familial adenomatous polyposis (FAP), caused by germline mutations in the APC tumor suppressor gene; these mutations similarly lead to unchecked Wnt/beta-catenin activity. The Notch signaling pathway is closely intertwined with Wnt/beta-catenin signaling in desmoid tumor biology: Notch activation contributes to tumor cell survival, proliferation, and the fibroblastic phenotype. By inhibiting gamma-secretase, nirogacestat prevents the release of the Notch intracellular domain (NICD), which normally translocates to the nucleus to regulate target gene transcription. This blockade interrupts the aberrant signaling that sustains desmoid tumor growth.
Ogsiveo is indicated for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. In clinical practice, not every patient with a desmoid tumor will be a candidate for Ogsiveo. International guidelines, including those from the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), generally recommend an initial strategy of active surveillance for newly diagnosed, asymptomatic desmoid tumors, because a significant proportion (approximately 20% to 30%) will stabilize or even spontaneously regress without intervention. Systemic therapy is reserved for tumors that progress on imaging, cause symptoms, threaten critical structures, or are unresectable.
The pivotal clinical evidence supporting Ogsiveo comes from the DeFi trial (NCT03785964), a randomized, double-blind, placebo-controlled phase 3 study that enrolled 142 adults with progressing desmoid tumors. Patients were randomized 1:1 to receive either nirogacestat 150 mg orally twice daily or matching placebo. The primary endpoint was progression-free survival (PFS), with key secondary endpoints including objective response rate, patient-reported pain, physical functioning, and safety.
- Progression-free survival: Nirogacestat reduced the risk of disease progression or death by 71% compared with placebo (hazard ratio 0.29; 95% CI 0.15 to 0.55; p < 0.001). The 2-year PFS rate was 76% with nirogacestat versus 44% with placebo, and the median PFS was not reached in the nirogacestat arm versus 15.1 months with placebo.
- Objective response rate: Among patients receiving nirogacestat, 41% achieved a confirmed objective response (tumor shrinkage of at least 30% on imaging), compared with only 8% for placebo. Seven percent of patients on nirogacestat achieved a complete response (complete disappearance of the tumor on imaging), versus 0% for placebo.
- Pain and quality of life: Nirogacestat produced statistically significant and clinically meaningful improvements in patient-reported pain (measured with the Numerical Rating Scale for worst pain), physical functioning, and role functioning compared with placebo. Pain improvements were observed within the first month of treatment and were sustained throughout the study.
These results, published in the New England Journal of Medicine in 2023, represent the most convincing evidence for a systemic therapy in desmoid tumors to date and led to the drug's inclusion in international guidelines as a preferred systemic treatment option for patients with progressing or symptomatic desmoid tumors. Earlier options such as tyrosine kinase inhibitors (e.g., sorafenib, pazopanib) and conventional cytotoxic chemotherapy (e.g., methotrexate plus vinblastine, doxorubicin-based regimens) remain alternatives but lack the large, randomized evidence base that supports Ogsiveo.
Desmoid tumors can be disabling even when they are not life-threatening, and treatment decisions often prioritize symptom control as much as tumor shrinkage. Ogsiveo is one of the first systemic therapies to demonstrate both objective tumor responses and robust improvements in pain and physical functioning in a prospective, placebo-controlled trial, which is why clinicians and patient advocacy groups regard its approval as a landmark in the management of this rare condition.
What Should You Know Before Taking Ogsiveo?
Contraindications
The primary contraindication to Ogsiveo is known hypersensitivity (allergy) to nirogacestat or to any of the other ingredients in the tablet formulation. If you have had a severe allergic reaction to this medication previously, you must not restart it. In addition, Ogsiveo must not be co-administered with strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers, or with P-glycoprotein (P-gp) inhibitors, as these can alter nirogacestat exposure to clinically dangerous levels. Concurrent use of these interacting medications should be avoided or managed with specialist guidance before starting Ogsiveo.
Warnings and Precautions
Ogsiveo can cause ovarian toxicity in females of reproductive potential, including reduced ovarian reserve, amenorrhea, ovarian cysts, and infertility that may or may not be reversible after treatment ends. In the DeFi trial, ovarian dysfunction occurred in the majority of premenopausal female participants. Discuss fertility preservation (e.g., oocyte or embryo cryopreservation) with a reproductive specialist before starting treatment if future pregnancy is desired.
Before starting Ogsiveo, you should discuss the following important safety considerations with your oncologist or specialist physician:
- Diarrhea: Diarrhea is one of the most common adverse events with Ogsiveo, occurring in approximately 84% of patients and reaching grade 3 severity in 16%. Most events respond to anti-diarrheal medications (such as loperamide), hydration, and dose adjustments. Patients should contact their healthcare provider for persistent, severe, or worsening diarrhea to prevent dehydration and electrolyte disturbances.
- Hepatotoxicity: Elevations in liver enzymes (AST, ALT, alkaline phosphatase) and bilirubin can occur during Ogsiveo therapy. Baseline liver function should be established before starting treatment and monitored regularly (e.g., monthly for the first 3 months, then periodically thereafter). Dose interruption or reduction is recommended for clinically significant abnormalities.
- Hypophosphatemia: Decreased blood phosphate levels are frequent with Ogsiveo and can cause muscle weakness, fatigue, and, rarely, cardiac or neurological complications. Phosphate levels should be monitored regularly, and oral phosphate supplementation may be required.
- Electrolyte disturbances: Decreases in potassium and magnesium can also occur and may contribute to muscle cramps or cardiac conduction abnormalities. Routine electrolyte monitoring is recommended.
- Embryo-fetal toxicity: Based on animal data and the mechanism of action (gamma-secretase and Notch signaling play essential roles in embryonic development), Ogsiveo can cause serious harm to an unborn baby. Pregnancy must be excluded before treatment and prevented during and after treatment.
- Photosensitivity: Ogsiveo can increase skin sensitivity to sunlight and other sources of ultraviolet light. Use high-SPF sunscreen, wear protective clothing, and avoid prolonged unprotected sun exposure during treatment.
Children and Adolescents
Ogsiveo is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of nirogacestat in pediatric patients have not been established. Desmoid tumors in children are managed by specialized pediatric oncology and sarcoma centers using different treatment approaches, and clinical trials evaluating nirogacestat in pediatric populations are ongoing.
Pregnancy and Breastfeeding
Ogsiveo can cause fetal harm and is not recommended during pregnancy. Pregnancy status must be verified before starting treatment in all females of reproductive potential. Effective non-hormonal contraception must be used during treatment and for at least 1 week after the final dose. Hormonal contraceptives are not recommended as a sole method because nirogacestat may reduce their effectiveness through CYP3A-mediated interactions. Male patients with female partners of reproductive potential should also discuss contraceptive precautions with their physician.
Breastfeeding is not recommended during Ogsiveo treatment and for at least 1 week after the final dose, because it is not known whether nirogacestat passes into human breast milk and because of the potential for serious adverse reactions in the breastfed infant. Women who wish to breastfeed should discuss alternatives with their healthcare provider.
Driving and Operating Machinery
Ogsiveo has not been specifically studied for effects on driving or operating machinery. However, fatigue, dizziness, headache, and diarrhea are common side effects that could impair these activities. If you experience any of these symptoms, refrain from driving or operating dangerous machinery until you feel well.
Important Information About Ingredients
Each Ogsiveo 50 mg film-coated tablet contains the active substance nirogacestat (as nirogacestat hydrobromide) together with standard pharmaceutical excipients, including microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and a film coating. Patients with known intolerance to any of these excipients should discuss the complete ingredient list with their pharmacist before starting treatment.
How Does Ogsiveo Interact with Other Drugs?
Unlike monoclonal antibodies, which have few pharmacokinetic drug interactions, oral small-molecule targeted therapies such as nirogacestat are typically metabolized by hepatic enzymes and can be affected by a wide range of other medications. Management of drug interactions is therefore a central part of safe Ogsiveo prescribing. A full medication review should be performed before initiating treatment and whenever a new medication (including over-the-counter products and herbal supplements) is added.
Major Interactions
The following drug interactions are considered clinically significant and generally require avoidance, substitution, or careful specialist management:
| Interacting Category | Examples | Effect | Recommendation |
|---|---|---|---|
| Strong CYP3A inhibitors | Itraconazole, ketoconazole, clarithromycin, ritonavir, grapefruit juice | Increase nirogacestat levels; higher toxicity risk | Avoid |
| Moderate CYP3A inhibitors | Erythromycin, diltiazem, verapamil, fluconazole, ciprofloxacin | Increase nirogacestat levels | Avoid |
| Strong CYP3A inducers | Rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort | Decrease nirogacestat levels; loss of efficacy | Avoid |
| Moderate CYP3A inducers | Efavirenz, bosentan, etravirine, modafinil | Decrease nirogacestat levels | Avoid |
| P-glycoprotein inhibitors | Amiodarone, cyclosporine, dronedarone, quinidine | Increase nirogacestat levels | Avoid |
| P-gp substrates (narrow therapeutic index) | Digoxin, dabigatran, fexofenadine | Nirogacestat inhibits P-gp; increased substrate exposure possible | Monitor and consider dose adjustment of the substrate |
Other Clinically Relevant Interactions
Gastric acid reducing agents can reduce the absorption of nirogacestat because its solubility is pH-dependent. This includes:
- Proton pump inhibitors (PPIs) such as omeprazole, esomeprazole, pantoprazole, and lansoprazole — avoid concurrent use if possible.
- Histamine H2 receptor antagonists such as famotidine and ranitidine — take Ogsiveo at least 2 hours before or 10 hours after the H2 antagonist.
- Locally acting antacids such as calcium carbonate, aluminum hydroxide, or magnesium hydroxide — separate administration by at least 2 hours before or 2 hours after Ogsiveo.
In addition, grapefruit, grapefruit juice, Seville oranges, and starfruit can inhibit intestinal CYP3A4 and should be avoided during Ogsiveo treatment. Patients should also inform their doctor about all herbal supplements, as products such as St. John's wort (a strong CYP3A inducer) and certain traditional medicines can have significant effects on nirogacestat exposure.
Nirogacestat may reduce the effectiveness of hormonal contraceptives (combined oral contraceptive pills, progesterone-only pills, transdermal patches, vaginal rings, and hormonal intrauterine systems) through CYP3A enzyme effects. Females of reproductive potential should use an effective non-hormonal contraceptive method (such as a copper intrauterine device or barrier methods) during treatment and for at least 1 week after the last dose.
Given the complexity of potential interactions, patients should always bring a complete medication list to every medical appointment and check with a pharmacist before starting any new prescription, over-the-counter, or herbal product while on Ogsiveo. The benefits of Ogsiveo can be preserved, and safety risks minimized, only when drug interactions are actively managed throughout the course of treatment.
What Is the Correct Dosage of Ogsiveo?
Ogsiveo must always be taken exactly as prescribed by your oncologist or sarcoma specialist. The recommended starting dose is based on the phase 3 DeFi trial, in which a fixed dose of 150 mg twice daily was associated with a 71% reduction in the risk of desmoid tumor progression. Because Ogsiveo is intended as continuous therapy rather than a short course, adherence is essential to maintain disease control, while side effects are managed through dose interruptions, dose reductions, and supportive care as needed.
Adults
The recommended dosage regimen for adults with progressing desmoid tumors is summarized in the table below. Ogsiveo is supplied as 50 mg film-coated tablets, and each dose consists of three tablets taken together.
| Parameter | Recommendation | Notes |
|---|---|---|
| Individual dose | 150 mg (three 50 mg tablets) | Swallow tablets whole with water |
| Frequency | Twice daily, approximately 12 hours apart | e.g., morning and evening |
| Total daily dose | 300 mg per day | 6 tablets in total per day |
| Food | With or without food | Avoid grapefruit and Seville oranges |
| Duration | Until disease progression or unacceptable toxicity | Typically months to years |
| First dose reduction | 100 mg twice daily | Two 50 mg tablets twice daily |
| Second dose reduction | 50 mg twice daily | One 50 mg tablet twice daily |
| Below lowest dose | Discontinue treatment | If 50 mg twice daily is not tolerated |
Tablets should be swallowed whole and must not be crushed, chewed, cut, or dissolved. If you are unable to swallow whole tablets, discuss alternative strategies with your healthcare team before changing how you take the medication. Ogsiveo can be taken with or without food, which is convenient for patients who experience nausea or appetite changes and prefer to take medications with meals.
Dose Modifications for Adverse Events
Dose interruptions and reductions are an expected part of Ogsiveo treatment for many patients. For moderate-to-severe diarrhea, significant elevations in liver enzymes, clinically meaningful hypophosphatemia, or other grade 3 or higher adverse reactions, your oncologist may temporarily interrupt Ogsiveo until symptoms resolve. Treatment can then be resumed at the same dose, at the first reduced dose level (100 mg twice daily), or at the second reduced dose level (50 mg twice daily), depending on the severity and type of toxicity. These adjustments allow most patients to continue benefiting from Ogsiveo while minimizing side effects.
Children and Adolescents
Ogsiveo is not approved and is not recommended for use in patients younger than 18 years of age because safety and efficacy have not been established. Pediatric dosing has not been determined. Children and adolescents with desmoid tumors should be referred to pediatric oncology centers with expertise in rare sarcomas and considered for clinical trials where appropriate.
Elderly Patients
Clinical trial data in patients aged 65 years and older are limited because desmoid tumors most commonly occur in younger adults. Available subgroup analyses have not identified overall differences in safety or efficacy between younger and older patients, but as with any oral targeted therapy, elderly patients may be more susceptible to side effects such as dehydration from diarrhea, electrolyte disturbances, and drug interactions arising from polypharmacy. No specific starting-dose adjustment is recommended based on age alone, but careful clinical monitoring is advised.
Renal and Hepatic Impairment
No dose adjustment is recommended for patients with mild renal or hepatic impairment based on pharmacokinetic modeling. Limited data are available in patients with moderate or severe renal impairment, moderate hepatic impairment (Child-Pugh B), or severe hepatic impairment (Child-Pugh C); specialist advice should be sought before starting Ogsiveo in these groups, and close monitoring is recommended.
Missed Dose
If you miss a dose of Ogsiveo, take it as soon as you remember on the same day, unless it is less than 6 hours before your next scheduled dose. In that case, skip the missed dose and resume the normal schedule with the next dose. Do not take two doses together to make up for a missed dose. If you vomit after taking a dose, do not take an additional dose; wait until the next scheduled administration.
Overdose
There is limited clinical experience with nirogacestat overdose. If you or someone you know takes more Ogsiveo than prescribed, contact emergency services, a poison control center, or your oncologist immediately. Treatment of overdose is supportive, with monitoring of hydration, electrolytes, liver function, and general clinical status. There is no specific antidote.
What Are the Side Effects of Ogsiveo?
Like all medications, Ogsiveo can cause side effects, although not every patient experiences them. In the phase 3 DeFi trial, adverse events were common but mostly mild to moderate in severity. The overall discontinuation rate due to adverse events was approximately 20%, and dose modifications (interruptions or reductions) were required in the majority of treated patients. Despite this, the benefit-risk profile is widely considered favorable given the severity and progression of untreated desmoid tumors.
The categories below present side effects by frequency, based on data from the DeFi trial and the post-marketing experience. Clinically important events such as ovarian dysfunction and laboratory abnormalities are described in more detail in the text following the grid.
Very Common
May affect more than 1 in 10 people
- Diarrhea
- Ovarian toxicity (females of reproductive potential)
- Rash (including maculopapular rash, dermatitis)
- Nausea
- Fatigue and asthenia
- Stomatitis (mouth sores) and mucositis
- Headache
- Abdominal pain
- Cough
- Alopecia (hair thinning or loss)
- Upper respiratory tract infection
- Dyspnea (shortness of breath)
- Decreased phosphate in blood
- Decreased potassium in blood
- Increased AST / ALT (liver enzymes)
- Decreased lymphocyte count
Common
May affect up to 1 in 10 people
- Vomiting
- Dyspepsia (indigestion)
- Dry mouth (xerostomia)
- Pruritus (itching)
- Photosensitivity reaction
- Nail disorders (changes in nail texture or color)
- Arthralgia (joint pain) and myalgia (muscle pain)
- Dizziness
- Amenorrhea or menstrual irregularities
- Ovarian cysts
- Hypomagnesemia
- Increased alkaline phosphatase
Uncommon
May affect up to 1 in 100 people
- Hepatotoxicity with clinically significant transaminase elevation
- Severe skin reactions requiring dose interruption
- Severe electrolyte disturbances requiring intravenous correction
- Neutropenia and other cytopenias
Rare
May affect up to 1 in 1,000 people
- Severe hypersensitivity reactions (including angioedema or anaphylaxis)
- Serious infections requiring hospitalization
- Drug-induced liver injury
Diarrhea is the most frequent adverse reaction, occurring in approximately 84% of patients in the DeFi trial, with about 16% experiencing grade 3 (severe) diarrhea. Onset is typically within the first few weeks of treatment. Proactive management is essential: patients are advised to take loperamide at the first sign of loose stools, maintain adequate hydration, avoid aggravating foods (such as high-fat, high-fiber, or spicy foods), and contact their care team if diarrhea persists for more than 24 hours or is associated with fever, blood in the stool, or severe cramping. Dose interruption and reduction typically bring symptoms under control.
Ovarian toxicity is a particularly important consideration for female patients of reproductive potential. In the DeFi trial, ovarian dysfunction — including reduced ovarian reserve markers (AMH), amenorrhea, ovarian cysts, and infertility — was reported in the majority of premenopausal women who received nirogacestat. Resolution was observed in many but not all patients after dose reduction or discontinuation, and recovery may take months. Because of these findings, fertility preservation (oocyte or embryo cryopreservation) should be discussed with a reproductive endocrinologist before initiating treatment in women who wish to preserve future fertility options.
Skin and hair changes are also common. Rash (often maculopapular and photosensitive in character) occurs in approximately two-thirds of patients and typically responds to topical corticosteroids, antihistamines, and sun protection measures. Hair thinning or loss (alopecia) and nail changes are usually reversible upon treatment discontinuation but can be distressing. Patients should use broad-spectrum high-SPF sunscreen and protective clothing during treatment to minimize photosensitivity reactions.
Laboratory abnormalities, including low blood phosphate, low potassium, low magnesium, elevated liver transaminases, and decreased lymphocyte counts, are monitored routinely during Ogsiveo therapy. Phosphate levels should be checked at baseline, then at regular intervals, with supplementation provided as needed. Liver function tests are typically monitored monthly for the first 3 months of treatment and then periodically; dose interruption or reduction is recommended for clinically significant elevations.
Most side effects can be managed with dose adjustments, supportive medications, and close monitoring, allowing the majority of patients to remain on treatment long enough to derive meaningful benefit. Patients are encouraged to report new or worsening symptoms promptly and to attend scheduled follow-up visits for clinical assessment and laboratory monitoring.
Contact your healthcare team urgently if you develop severe or persistent diarrhea, signs of dehydration (dizziness, dark urine, little or no urination), yellowing of the skin or eyes (jaundice), severe abdominal pain, unexplained bruising or bleeding, a widespread or blistering rash, new difficulty breathing, chest pain, or signs of a severe allergic reaction (facial swelling, difficulty breathing, widespread hives). For suspected allergic reactions or severe dehydration, seek emergency medical care immediately.
How Should You Store Ogsiveo?
Correct storage of Ogsiveo helps to preserve the potency and stability of the active ingredient, nirogacestat, over the full shelf life of the product. Follow these storage and handling recommendations carefully:
- Temperature: Store at controlled room temperature of 20–25 °C (68–77 °F). Brief excursions between 15 °C and 30 °C (59–86 °F) are permitted during transport or normal use.
- Original container: Keep tablets in the original bottle or blister packaging, which is designed to protect from moisture and light. The container may include a desiccant (moisture absorber) — do not remove or swallow it.
- Humidity: Protect from excessive moisture. Do not store in bathrooms, near sinks, or in other humid environments.
- Light: Protect from direct sunlight. Do not store on windowsills or in hot cars.
- Out of reach of children: Ogsiveo should be stored in a secure location inaccessible to children and pets. Accidental ingestion by children could cause serious harm.
- Expiration date: Do not use Ogsiveo after the expiration date printed on the bottle or outer packaging. The expiration date refers to the last day of that month.
- Damaged packaging or tablets: Do not use tablets that appear cracked, broken, discolored, or otherwise damaged. Contact your pharmacist if you have any concerns about the appearance of the tablets.
When traveling with Ogsiveo, keep the medication in its original container and carry it in your hand luggage to avoid extreme temperatures in the cargo hold of aircraft. Take enough supply for the entire trip plus a reserve, and carry a copy of your prescription or a letter from your physician, particularly when crossing international borders.
Disposal: Unused or expired Ogsiveo should not be disposed of via household rubbish or flushed down the toilet. Return unused medication to a pharmacy or use a medication take-back program, if available in your region. Proper disposal helps to protect other people and the environment from accidental exposure and to prevent contamination of water supplies.
What Does Ogsiveo Contain?
Knowing the complete composition of your medication is important, particularly if you have known allergies or sensitivities to common pharmaceutical excipients. The table below outlines the active and inactive ingredients in Ogsiveo 50 mg film-coated tablets.
Active Ingredient
The active substance is nirogacestat, supplied as nirogacestat hydrobromide. Each tablet contains the equivalent of 50 mg of nirogacestat free base. Nirogacestat is a selective, small-molecule inhibitor of gamma-secretase, a transmembrane protease complex required for the activation of Notch signaling.
Inactive Ingredients (Excipients)
| Ingredient | Role | Notes |
|---|---|---|
| Nirogacestat hydrobromide | Active substance | 50 mg nirogacestat free base per tablet |
| Microcrystalline cellulose | Filler / binder | Common excipient |
| Croscarmellose sodium | Disintegrant | Helps the tablet break down |
| Magnesium stearate | Lubricant | Improves manufacturability |
| Film coating (hypromellose, titanium dioxide, polyethylene glycol, colorants) | Tablet coating | Improves stability and swallowability |
Appearance and Pack Sizes
Ogsiveo is supplied as film-coated tablets of 50 mg. Pack sizes and tablet appearance may vary by country and market; patients should refer to the specific package insert provided with their prescription. Typically, tablets are dispensed in bottles containing a supply sufficient for approximately one month of treatment at the standard dose of 300 mg per day (corresponding to approximately 180 tablets).
Marketing Authorization Holder and Manufacturer
Ogsiveo is developed and marketed by SpringWorks Therapeutics, Inc. (Stamford, Connecticut, USA). The product received FDA approval in the United States on 27 November 2023 under accelerated approval for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. Marketing authorization and availability in other regions are evolving; patients should consult their specialist or healthcare system for information on access in their country.
Frequently Asked Questions About Ogsiveo
Ogsiveo (nirogacestat) is a prescription oral medication used to treat adults with progressing desmoid tumors who require systemic treatment. Desmoid tumors, also called desmoid-type fibromatosis or aggressive fibromatosis, are rare soft-tissue growths that can invade surrounding muscle, nerves, and vessels, causing severe pain and functional impairment. Ogsiveo is a gamma-secretase inhibitor that blocks Notch signaling, a pathway frequently dysregulated in desmoid tumors due to mutations in the CTNNB1 or APC genes. It is the first drug approved specifically for desmoid tumors.
In the phase 3 DeFi trial, Ogsiveo reduced the risk of desmoid tumor progression or death by 71% compared with placebo. The objective response rate (measurable tumor shrinkage of at least 30%) was 41% with Ogsiveo versus 8% with placebo, and 7% of patients achieved a complete response. Patient-reported outcomes showed significant improvements in pain, physical functioning, and role functioning, many of which were evident within the first 1 to 3 months of treatment. Responses tend to deepen and become more apparent over 6 to 12 months of continued therapy.
Take Ogsiveo exactly as prescribed. The standard dose is three 50 mg tablets swallowed whole with water, twice daily (morning and evening), approximately 12 hours apart, with or without food. Do not crush, chew, cut, or split the tablets. Avoid grapefruit, grapefruit juice, Seville oranges, and starfruit, as they can increase drug levels. If you miss a dose, take it as soon as you remember on the same day unless it is less than 6 hours before the next scheduled dose, in which case skip it and resume the normal schedule. Do not take a double dose to make up for a missed one.
Yes. Ogsiveo can cause ovarian toxicity in females of reproductive potential, including reduced ovarian reserve, amenorrhea, ovarian cysts, and infertility that may or may not be reversible after treatment ends. In the DeFi trial, ovarian dysfunction occurred in the majority of premenopausal women. Because of this, it is essential to discuss fertility preservation options — such as egg or embryo freezing — with a reproductive endocrinologist before starting Ogsiveo if future pregnancy is important to you. The effects of nirogacestat on male fertility are not fully characterized, but effective contraception is recommended for male patients with partners of reproductive potential.
Diarrhea affects most patients taking Ogsiveo and is typically manageable with proactive care. At the first sign of loose stools, start loperamide (an over-the-counter anti-diarrheal) according to package directions, drink plenty of fluids including oral rehydration solutions, and avoid high-fat, high-fiber, or spicy foods. If diarrhea persists for more than 24 hours, worsens, or is accompanied by fever, blood in the stool, severe cramping, or signs of dehydration (dizziness, reduced urination), contact your healthcare team promptly. They may recommend temporary dose interruption, dose reduction, or additional supportive medications.
Ogsiveo is generally continued for as long as it is controlling the desmoid tumor and you are tolerating the medication. This can mean many months to several years of therapy. Your oncologist will use regular imaging (typically MRI every 3 to 6 months) and clinical assessments to monitor treatment response. If the tumor progresses despite therapy, or if intolerable side effects develop that cannot be managed with dose adjustments and supportive care, your doctor will discuss alternative treatment options, which may include tyrosine kinase inhibitors, chemotherapy, surgery, or radiation in selected cases.
Many common medications and supplements can interact with Ogsiveo through CYP3A enzymes and the P-glycoprotein transporter. Avoid strong and moderate CYP3A inhibitors (such as clarithromycin, diltiazem, itraconazole), strong and moderate CYP3A inducers (such as rifampin, phenytoin, St. John's wort), and P-glycoprotein inhibitors (such as amiodarone, cyclosporine). Proton pump inhibitors and H2 blockers can reduce absorption. Always give your oncologist and pharmacist a complete list of every medication, herbal product, and supplement you use, and check before starting anything new.
References
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