Generic Larotrectinib Capsules Gain Tentative FDA Approval

Alembic Pharmaceuticals Limited announced on June 11, 2026, that it has received tentative approval from the US FDA for an abbreviated new drug application (ANDA) for larotrectinib (Vitrakvi) capsules, 25 mg and 100 mg. Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor indicated for adults and pediatric patients with neurotrophic receptor tyrosine kinase (NTRK) gene fusion–positive solid tumors. The approved generic is therapeutically equivalent to the reference listed drug, marketed by Bayer Healthcare Pharmaceuticals Inc.¹

The company is the sole first applicant to have filed an ANDA for larotrectinib capsules containing a Paragraph IV certification under the provisions of the Hatch-Waxman Act. Upon conversion to final approval, which requires resolution of any outstanding patent or exclusivity issues, Alembic may be eligible for 180 days of generic marketing exclusivity in the United States. The tentative designation indicates that the application is otherwise approvable but cannot receive final approval at this time, typically because the reference listed drug retains market exclusivity protections.

Background on Larotrectinib and Its Regulatory History

Larotrectinib is a first-in-class, highly selective, orally administered TRK inhibitor that targets the 3 tropomyosin receptor kinase proteins—TRKA, TRKB, and TRKC—encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively. Chromosomal translocations involving these genes produce oncogenic TRK fusion proteins that act as constitutively active drivers of tumor growth across a diverse array of histologic types in both adults and children.

The FDA granted larotrectinib accelerated approval on November 26, 2018, based on pooled data from 3 clinical trials: a phase 1 adult trial (NCT02122913; LOXO-TRK-14001), a phase 1/2 pediatric trial (NCT02637687; SCOUT), and a phase 3 adult and adolescent basket trial (NCT02576431; NAVIGATE).² In the initial analysis of 55 patients spanning a broad range of tumor types, the overall response rate (ORR) was 75% (95% CI, 61%-85%), with a 22% complete response (CR) rate.1 At 1 year, 71% of responses remained ongoing and more than half of patients were progression free. This approval was notable as the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval.

Full approval followed in April 2025, based on pooled efficacy and safety data from the same 3 trials encompassing 339 adult and pediatric patients with unresectable or metastatic NTRK gene fusion–positive solid tumors.³ In the efficacy-evaluable population (n = 180), the ORR was 57% (95% CI, 50%-65%). At a median follow-up of 32.3 months, the median duration of response (DOR) was 43.3 months (95% CI, 29.2-not evaluable); the 24- and 48-month DOR rates were 66% and 48%, respectively. Median progression-free survival was 24.6 months (95% CI, 11.3-35.5) at a median follow-up of 28.5 months.³

Potential Clinical and Access Implications

The indication for larotrectinib is tissue agnostic and requires the demonstration of an NTRK gene fusion without a known acquired resistance mutation in a solid tumor that is metastatic or where surgical resection would likely result in severe morbidity, and for which no satisfactory alternative treatments exist or disease has progressed following prior treatment. For clinicians, this underscores the importance of comprehensive molecular testing, including next-generation sequencing panels capable of detecting NTRK gene fusions, as part of standard workup for patients with advanced solid tumors.

The availability of a generic formulation, if and when final approval is granted, could meaningfully reduce patient out-of-pocket costs and improve access in settings where formulary restrictions or cost-sharing have been barriers to prescribing.

REFERENCES

1. Alembic Pharmaceuticals Limited announces USFDA Tentative Approval for Larotrectinib Capsules, 25 mg and 100 mg. News release. Alembic Pharmaceuticals. June 11, 2026. Accessed June 11, 2026.

2. FDA approves larotrectinib for solid tumors with NTRK gene fusions. News release. US FDA. Updated December 14, 2018. Accessed June 11, 2026. https://tinyurl.com/mrx693w5

3. U.S. FDA Grants Full Approval of VITRAKVI® (larotrectinib) for Adult and Pediatric Patients with NTRK Gene Fusion-Positive Solid Tumors. News release. Bayer. April 10, 2025. Accessed June 11, 2026. https://tinyurl.com/9kjru36p