Blueprint Announces FDA Approval of GAVRETO for Metastatic Non-Small Cell Lung Cancer

Blueprint Medicines announced the U.S. Food and Drug Administration (FDA) has approved GAVRETO™ (pralsetinib) for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) 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. Under Blueprint Medicines' collaboration with Roche, Blueprint Medicines and Genentech, a member of the Roche Group, will co-commercialize GAVRETO in the U.S.

GAVRETO 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 NSCLC. Currently, RET is one of seven NSCLC biomarkers that can be targeted with an FDA-approved therapy.

"Targeted therapies have dramatically improved care for patients with non-small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or GAVRETO, marks another milestone in a paradigm shift toward precision medicine," said Vivek Subbiah, M.D., 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. "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. 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 is the second breakthrough therapy discovered by Blueprint Medicines that has received FDA approval in 2020, less than 10 years since the company started operations. This progress reflects the power of our scientific platform, our focus on delivering transformative outcomes to patients and our urgency to address important medical needs," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "We are working with our partner Genentech to rapidly bring GAVRETO to healthcare providers and patients in the U.S., applying our complementary capabilities to support patient identification and access to treatment. Ultimately, we aim to accelerate the identification of patients with RET fusion-positive non-small cell lung cancer and enable them to rapidly access treatment with GAVRETO."

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 (ORR) was 57 percent (95% CI: 46%, 68%) with a 5.7 percent complete response (CR) rate, and the median duration of response (DOR) was not estimable (95% CI: 15.2 months, not estimable). In 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, the ORR was 70 percent (95% CI: 50%, 86%) with an 11 percent CR rate, and the median DOR was 9.0 months (95% CI: 6.3 months, not estimable). 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.

"We applaud therapeutic advancements like GAVRETO that allow lung cancer treatment to be personalized based on the molecular drivers in a person's tumor," said Andrea Ferris, President and CEO of LUNGevity. "There are now a number of tumor-specific gene alterations that can be targeted with FDA-approved therapies, reflecting an important inflection point supporting the widespread use of comprehensive biomarker testing. At LUNGevity, we want to empower patients and their families to discuss biomarker testing with clinicians prior to initiating treatment."

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. In the ARROW trial, RET fusions were detected using next-generation sequencing, FISH or other methods.

Blueprint Medicines and Genentech plan to make GAVRETO available in the U.S. within one week. GAVRETO will be available in a 100 mg dose strength, and the recommended starting dose is 400 mg once daily.