FDA approves Lutathera for gastroenteropancreatic neuroendocrine tumors.- Advanced Accelerator Applications.

Advanced Accelerator Applications, a subsidiary of Novartis Groupe S.A., has received FDA approval of its new drug application (NDA) for Lutathera (lutetium Lu 177 dotatate) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors, in adults. Lutathera, which received orphan drug designation from the FDA, is a first-in-class drug and the first available FDA-approved Peptide Receptor Radionuclide Therapy (PRRT), a form of treatment comprising of a targeting molecule that carries a radioactive component.

The approval of Lutathera is based on results of a randomized pivotal Phase III study, NETTER-1 that compared treatment using Lutathera plus best standard of care (octreotide LAR 30mg every four weeks) to 60 mg of octreotide LAR, also dosed every four weeks, in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors, as well as a subset of efficacy and safety data from an international, single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, Netherlands in more than 1,200 patients with somatostatin receptor positive tumors.

The NETTER-1 study met its primary endpoint, showing a 79% reduction in risk of disease progression or death using Lutathera compared to 60 mg octreotide LAR (hazard ratio 0.21, 95% CI: 0.13-0.32; p<0.0001). median pfs was not reached in the lutathera arm compared to 8.5 months for the 60 mg octreotide lar arm. a pre-planned interim overall survival analysis determined that lutathera treatment lead to a 48% reduction in the estimated risk of death (hazard ratio 0.52, 95% ci: 0.32-0.84) compared to treatment with 60 mg octreotide lar. the objective response rate, composed of complete and partial responses, was 13% for the lutathera arm compared to 4% in the octreotide lar 60mg arm (p><0.0148). the most common grade 3-4 adverse reactions occurring with a greater frequency among patients in the netter-1 study receiving lutathera with octreotide compared to patients receiving high-dose octreotide include: lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia and hypokalemia (4% each).>