Introduction
Nirogacestat also known by the brand name Ogsiveo is a targeted therapy approved by the FDA on November 27, 2023 for the treatment of adults with desmoid tumors, this is the first approved treatment for desmoid tumors nirogacestat was approved in the USA for use in adult patients with progressing desmoid tumours who require systemic treatment. Desmoid tumors are rare, non-metastasizing soft tissue tumors. They arise from fibroblasts and can occur in any part of the body, commonly in the abdomen, limbs, and thoracic areas.
Desmoid tumor have an incidence of 2.10 to 5.36 cases per million person-years, primarily affecting individuals aged 20 to 44 years but can occur at any age. Women are 2.2 to 3.9 times more likely to develop Desmoid tumor, with risk factors including recent pregnancy, oral contraceptive use, antecedent trauma, and high oestrogen levels.
Mechanism of Action
Nirogacestat is a gamma-secretase inhibitor (GSI). Gamma-secretase is an enzyme involved in the Notch signalling pathway, which is crucial for cell differentiation and proliferation. By inhibiting gamma-secretase, nirogacestat disrupts the growth signals in desmoid tumors, leading to tumor shrinkage and reduced progression.
Indications
Nirogacestat is indicated for adult patients with desmoid tumors that are not amenable to surgery or have recurred after surgical treatment.
Dosage and Administration
Nirogacestat is administered orally. The typical dosage is 150 mg taken twice daily. The exact dosage and treatment schedule should be determined by the healthcare provider based on the patient’s condition and response to treatment.
Clinical Trial Results
The approval of nirogacestat was based on the results of the phase 3 DeFi trial, which showed significant benefits for patients with desmoid tumors:
- Tumor Reduction: 41% of patients experienced significant tumor shrinkage.
- Progression-Free Survival: Over 75% of patients had no tumor progression after two years on nirogacestat, compared to 44% in the placebo group.
Patient-Reported Outcomes: Patients reported improvements in pain, desmoid tumor-specific symptoms, and overall quality of life.
Side Effects
Common side effects of nirogacestat include:
- Diarrhoea
- Nausea
- Fatigue
- Rash
- Abdominal pain
- Stomatitis (inflammation of the mouth)
- Ovarian dysfunction in women of reproductive age (generally resolves after discontinuation)
Serious adverse effects occurred in about 20% of patients, leading to discontinuation in some cases.
Monitoring and Follow-Up
Patients on nirogacestat will require regular monitoring to assess the drug’s effectiveness and manage any side effects. This includes:
- Regular physical exams
- Imaging studies (e.g., MRI or CT scans)
- Blood tests to monitor for potential side effects
Patient Support
Patients taking nirogacestat should have access to comprehensive support services, including:
- Medical Support: Regular follow-ups with oncologists and specialists.
- Psychological Support: Counselling or support groups.
- Nutritional Support: Dietary advice to manage side effects like nausea and loss of appetite.
Conclusion
Nirogacestat offers a new treatment option for patients with desmoid tumors, providing significant benefits in tumor reduction and quality of life. Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade.