Vientiane, Laos - May 30, 2024 - BIGBEARPharma, a leading biopharmaceutical company focused on developing and commercializing innovative cancer therapies, announced that larotrectinib oral capsules have been approved by the Lao Ministry of Health. Larotrectinib is marketed under the brand name LARODX. Lao Registration No.: 04L1086/24 for 100mg; Lao Registration No.: 04L1087/24 for 25mg.
Approved Drug
Larotrectinib is a potent, oral, selective tropomyosin receptor kinase (TRK) inhibitor designed to directly target TRK (including TRKA, TRKB, and TRKC), shutting off the signaling pathway that drives the growth of TRK fusion-positive tumors.
Larotrectinib is a "tumor-agnostic" therapy. It is the world's first oral TRK inhibitor specifically designed for cancer patients with NTRK gene fusions. NTRK gene fusions can be found in a variety of solid tumor types, including pancreatic cancer, thyroid cancer, salivary gland cancer, breast cancer, colorectal cancer, lung cancer, etc. Particularly in some rare cancers, such as infantile fibrosarcoma, secretory-like breast carcinoma, and secretory breast carcinoma, the incidence of NTRK gene fusions can exceed 90%. Therefore, TRK inhibitors have broad-spectrum anti-tumor activity.
Indications
Presence of a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation;
Tumor is metastatic or surgical resection is likely to result in severe complications;
No satisfactory alternative treatment options, or disease progression after treatment;
Patient selection for treatment should be based on FDA-approved detection methods.
Dosage and Administration
Select patients for treatment with larotrectinib based on the presence of an NTRK gene fusion.
Recommended dosage for adult and pediatric patients with body surface area (BSA) ≥ 1 square meter: 100 mg orally twice daily.
Recommended dosage for pediatric patients with BSA < 1 square meter: 100 mg/m² orally twice daily.
Common (≥20%) Adverse Reactions
Increased AST, increased ALT, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, fever, diarrhea, nausea, abdominal pain, dizziness, and rash.
Warnings and Precautions
1. Neurologic Effects
Neurologic adverse reactions (i.e., dizziness, cognitive impairment, mood disorders, sleep disorders) were reported in 42% of patients; 3.9% experienced Grade 3-4 severity. Median time to onset of cognitive impairment (reported in 11% of patients) was 5.6 months (range: 2 days to 41 months). Median time to onset of mood disorders (reported in 14% of patients) was 3.9 months (range: 1 day to 40.5 months).
2. Bone Fractures
Bone fractures have been reported, mostly associated with minor or moderate trauma. Median time to fracture was 11.6 months (range: 0.9-45.8 months). There are no data on the effect of larotrectinib on fracture healing or future fracture risk. Evaluate patients promptly for signs or symptoms of potential fractures (e.g., pain, change in mobility, deformity).
3. Hepatotoxicity
Elevations in ALT or AST have been reported. Median time to onset was 2.1-2.3 months (range: 1 day to 4.3 years). Monitor liver function tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter or more frequently as clinically indicated.
4. Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action and results from animal studies, larotrectinib can cause fetal harm. Animal studies have demonstrated embryofetal toxicity and teratogenicity. Avoid pregnancy during treatment and for at least 1 week after the final dose.
