FDA Approves Blueprint Medicines and Genentech’s Gavreto for the Treatment of Rare Lung Cancer

Rare Daily Staff

The U.S. Food and Drug Administration has approved Gavreto for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer as detected by an FDA approved test.

The approval is based on data from the phase 1/2 ARROW clinical trial, which showed efficacy for Gavreto in patients with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. RET-fusion positive patients make up 1 to 2 percent of patients with NSCLC.

Gavreto (pralsetinib) is a once-daily oral RET-targeted therapy developed by Blueprint Medicines. It is designed to selectively and potently inhibit RET alterations that drive many cancer types, including approximately 1 to 2 percent of patients with non-small cell lung cancer (NSCLC). Currently, RET is one of seven NSCLC biomarkers that can be targeted with an FDA-approved therapy.

“Patients treated with Gavreto had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” said Vivek Subbiah, associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center, and an investigator on the ARROW trial. “We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive non-small cell lung cancer, who have historically had limited treatment options.”

Gavreto was granted accelerated approval by the FDA, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In 87 patients previously treated with platinum-based chemotherapy, the overall response rate was 57 percent with a 5.7 percent complete response rate, and the median duration of response was not estimable.

In 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, the overall response rate was 70 percent with an 11 percent complete response rate, and the median duration of response was 9.0 months.

Gavreto has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk of impaired wound healing and risk of embryo-fetal toxicity.

Biomarker testing for RET is the only way to identify patients with metastatic NSCLC who are candidates for treatment with Gavreto. RET fusions can be identified with available biomarker tests, including next-generation sequencing with tumor tissue or liquid biopsies.

Under Blueprint Medicines’ collaboration with Roche, Blueprint Medicines and Genentech, a member of the Roche Group, will co-commercialize Gavreto in the United States. The companies plan to make Gavreto available in the United States within one week, and are pricing it at monthly cost of $19,250.

Blueprint Medicines is providing a patient support program that offers access and affordability solutions for individuals receiving the drug.

At the same time Blueprint announced pralsetinib’s marketing approval in RET fusion-positive NSCLC, the company said the FDA has accepted its NDA for pralsetinib for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer.

Photo: Vivek Subbiah, associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center, and an investigator on the ARROW trial