FDA Approvals Roundup: Gavreto and Trulicity

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).

New approval
Gavreto approved for metastatic lung cancer with RET gene fusions
Blueprint Medicines’ Gavreto (pralsetinib capsules) has been granted accelerated approval for treating adults with metastatic non‒small cell lung cancer (NSCLC) whose tumors test positive for rearranged during transfection (RET) fusion in an accompanying biomarker assay.
 
The assay, Life Technologies’ Oncomine Dx Target Test, received simultaneous approval. Gavreto acts by targeting RET alterations, including fusions and mutations, which fuel the disease trajectory in many cancers. It is the second RET-targeted therapy approved this year, after the May approval of Loxo Oncology’s Retevmo (selpercatinib) for NSCLC and medullary and other types of thyroid cancers.
 
Approval of the oral precision therapy was based on efficacy findings in the phase 1/2, multicenter, open-label, multicohort, interventional ARROW trial in a cohort of 87 patients whose tumors had RET alterations and who had received previous platinum-based therapy. Main efficacy outcome measures were overall response rate (ORR) and response duration with Gavreto. The ORR was 57% (95% confidence interval, 46%-68%; partial response, 52%; complete response, 5.7%), and of the responders, 80% had responses of 6 months or longer. In 27 never-treated patients, ORR was 70% (95% CI, 50%-86%), of whom 58% had responses of 6 months or longer.
 
The application for this indication was granted priority review, which used the assessment aid. It was also granted breakthrough therapy and orphan drug designations. Because the application received accelerated approval based on phase 1/2 ORR and response duration findings, continued approval of the indication may be contingent on confirmatory clinical trial findings. The application was approved almost 3 months ahead of the agency’s stated goal date.
 
Genentech and Blueprint Medicines will co-commercialize Gavreto in the US.
 
The agency also granted priority review to Gavreto for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer, which are also being evaluated in the continuing ARROW trial.
 
New indications
Trulicity okayed for additional doses as type 2 diabetes therapy
Eli Lilly’s Trulicity (dulaglutide injection) has received approval for additional, once-weekly doses of 3.0 mg and 4.5 mg for improving glycemic control in adults with type 2 diabetes.
 
The glucagon-like peptide 1 receptor agonist was originally approved in 2014 as a once-weekly dose of 1.5 mg, together with diet and exercise, for the indicated population.
 
Findings from the AWARD-11 trial showed that the 3.0-mg and 4.5-mg doses resulted in improved, dose-related glycemic control, as well as greater weight loss. The expanded approval was based on findings from the phase 3, randomized, double-blind, parallel-arm trial, which evaluated the efficacy and safety of once-weekly Trulicity 3.0 mg and 4.5 mg compared with Trulicity 1.5 mg in 1,842 participants with inadequately controlled type 2 diabetes. The primary endpoint was reduction in hemoglobin A1c (HbA1c) level with the investigational doses at 36 weeks after baseline. A secondary endpoint included change in mean body weight during the same period.
 
 At 36 weeks, for the subset of patients who remained on-treatment throughout the study, patients receiving the once-weekly, 4.5-mg dose of Trulicity, showed a reduction of 1.9% in HbA1c level and 10.4 pounds in weight, from baseline, compared with those receiving 3.0 mg (-1.7% and -8.8 pounds, respectively) and those receiving 1.5 mg (-1.5% and -6.8 pounds).
 
Results from AWARD-11 are also under review by the European Medicines Agency's Committee for Medicinal Products for Human Use.