Ogsiveo

Ogsiveo (nirogacestat) is an oral, selective, gamma-secretase inhibitor that may be used to treat adults with progressing desmoid tumors who require systemic treatment.

Desmoid tumors are rare and aggressive tumors of the soft tissues. Sometimes referred to as aggressive fibromatosis or desmoid fibromatosis, these soft tissue tumors can be serious, debilitating, and in rare cases, life-threatening.

Nirogacestat works by inhibiting gamma-secretase, an enzyme that cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to the growth of desmoid tumors.

Ogsiveo was FDA-approved on November 27, 2023.

Diarrhea is common, occurring in 84% of patients in clinical trials; 16% reported Grade 3 events (severe diarrhea). The median time to the first diarrhea event was 9 days (range: 2 to 434 days). Tell your healthcare provider if you develop any symptoms of diarrhea. You may need treatment with antidiarrheals and your dosage may need to be modified if it is severe.

Ogsiveo may impact female fertility and the menstrual cycle. Tell your doctor if you notice any changes in your menstrual cycle or develop symptoms of estrogen deficiency, such as hot flashes, night sweats, and vaginal dryness.

May cause liver toxicity. ALT or AST elevations occurred in 30% and 33% of patients who received Ogsiveo in clinical trials, some elevations were 5 times the upper limit of normal. Your doctor will monitor your liver function tests regularly and modify your dosage as recommended.

New non-melanoma skin cancers can occur in patients treated with Ogsiveo; trials have reported an incidence rate of 2.9% for cutaneous squamous cell carcinoma and 1.4% for basal cell carcinoma. Regular skin cancer checks should be conducted before starting treatment and throughout treatment.

Electrolyte abnormalities can occur in patients treated with Ogsiveo, such as low phosphate, and potassium levels. Your healthcare provider will monitor your phosphate and potassium levels regularly and supplement and modify your dosage as necessary.

Severe allergic reactions. Ogsiveo can cause allergic reactions that can be severe. Tell your healthcare provider right away if you develop any signs or symptoms of a severe allergic reaction, such as skin rash, itching, hives, chest pain, fast heart rate, wheezing or trouble breathing, swelling of the face, eyes, lips, tongue or throat, dizziness, fever, or muscle or joint pain.

Ogsiveo can cause fetal harm when administered to pregnant women. Females and males of reproductive potential must use effective contraception during treatment and for one week afterward.

It is not known if Ogsiveo is safe and effective in children.

Tell your doctor if you:

• have liver disease
• are dehydrated or have electrolyte problems
• have a history of skin cancer
• are pregnant or intend to become pregnant
• are breastfeeding.

Pregnancy

Ogsiveo can harm your unborn baby. Tell your healthcare provider if you become pregnant or think you may be pregnant during treatment.

Females who can become pregnant:

• Your healthcare provider will give you a pregnancy test before you start treatment.
• You should use effective birth control (contraception) during treatment and for 1 week after the last dose. If you use a birth control method that contains hormones (such as pills, injections, or patches), an additional barrier method of contraception (such as a condom or diaphragm) is recommended, as hormonal methods may not work as well during treatment. Talk to your healthcare provider about birth control methods that may be right for you.
• Stop taking Ogsiveo and tell your healthcare provider right away if you inadvertently become pregnant.

Males with female partners who can become pregnant should use effective birth control (contraception) during treatment with Ogsiveo and for 1 week after the last dose.

Breastfeeding

It is not known if Ogsiveo passes into your breast milk. Do not breastfeed during treatment and for 1 week after the last dose.

Ogsiveo can cause serious side effects, including:

• Diarrhea. Diarrhea is common during treatment and may sometimes be severe. Your healthcare provider may tell you to drink more fluids or may tell you to take antidiarrheal medicines. Tell your healthcare provider right away if you have diarrhea that lasts longer than a few days and does not get better after taking antidiarrheal medicines.
• Ovarian problems. Females who can become pregnant may have ovarian problems and changes in their menstrual cycle during treatment. Ogsiveo may affect fertility which may affect your ability to have a child. Tell your healthcare provider if you have any changes in your menstrual cycle or any hot flashes, night sweats, or vaginal dryness during treatment.
• Liver problems. Ogsiveo can cause an increase in liver enzymes. Your healthcare provider will do blood tests to check your liver function before you start and during your treatment.
• New Non-Melanoma Skin Cancers. Your healthcare provider will do skin exams before and during treatment with Ogsiveo if you are at risk for skin cancer. Tell your healthcare provider if you have any new or changing skin lesions.
• Electrolyte (salt) problems. Your healthcare provider will do blood tests to check your phosphate and potassium levels during treatment and may give you medicines to treat low phosphate or low potassium if needed. Tell your healthcare provider if you develop any muscle pain or weakness.
• Serious allergic reactions. Ogsiveo can cause allergic reactions that can be severe. Tell your healthcare provider right away if you develop any signs or symptoms of a severe allergic reaction, including skin rash, itching, hives, chest pain, fast heart rate, wheezing or trouble breathing, swelling of the face, eyes, lips, tongue or throat, dizziness or lightheadedness, fever, or muscle or joint pain.

The most common side effects affecting more than 15% of people taking Ogsiveo are:

• Diarrhea
• Ovarian problems
• Rash
• Nausea
• Fatigue
• Mouth sores (stomatitis)
• Headache
• Stomach (abdominal) pain
• Cough
• Hair loss (alopecia)
• Upper respiratory tract infection and shortness of breath (dyspnea).

The most common laboratory abnormalities affecting 15% or more people include decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.

To report suspected adverse reactions, contact SpringWorks Therapeutics Inc. at 1-888-400-7989 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Ogsiveo is taken by mouth.

• The recommended dosage is 150 mg orally twice daily.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment if you develop side effects.
• May be taken with or without food.
• Swallow tablets whole. Do not break, crush, or chew the tablets.
• If you take an antacid medicine, take Ogsiveo 2 hours before or 2 hours after taking the antacid.

If you miss a dose or vomit after taking a dose of Ogsiveo, take your next dose at your regular time. Do not take 2 doses to make up the dose.

Avoid eating or drinking grapefruit products, Seville oranges, and starfruit during treatment with Ogsiveo.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Avoid:

• Strong or moderate CYP3A inhibitors such as grapefruit juice, erythromycin, ketoconazole, clarithromycin, and verapamil
• Strong or moderate CYP3A inducers such as glucocorticoids, rifampin, carbamazepine, phenobarbital, and phenytoin.
• Proton pump inhibitors (PPIs) and H2 blockers.

Ask your healthcare provider if you are not sure if you take one of these medicines.

If you take an antacid medicine, take Ogsiveo 2 hours before or 2 hours after taking the antacid.

Avoid starfruit, Seville oranges, grapefruit, and juice from any of these fruits when taking Ogsiveo.

See the prescribing information for a full list of interactions.

Store at room temperature between 68°F to 77°F (20°C to 25°C).

Keep out of reach of children.

Active ingredient: nirogacestat

Inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate type A.

Film coating ingredients: FD&C yellow #6/sunset yellow FCF aluminum lake, glycerol monocaprylocaprate type 1/mono/diglycerides, iron oxide yellow, macrogol (PEG) polyvinyl alcohol graft copolymer, polyvinyl alcohol – partially hydrolyzed, talc, and titanium dioxide.

Available as 100 mg and 150 mg tablets.

SpringWorks Therapeutics, Inc.