U.S., EU and Japan Health Authorities Accept Regulatory Submissions for Review of Pfizer’s Third-generation ALK Inhibitor Lorlatinib

Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) accepted and granted Priority Review to the company’s New Drug Application for lorlatinib. Lorlatinib is an investigational, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC), previously treated with one or more ALK TKIs. The European Medicines Agency and the Japan Pharmaceutical and Medical Devices Agency have also accepted marketing applications for the use of lorlatinib.

“Treatment resistance resulting in disease progression is a major challenge faced by patients with ALK-positive metastatic NSCLC. Lorlatinib was developed by Pfizer scientists with the specific goal of overcoming resistance to first- and second-generation ALK-targeted therapies,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. “The encouraging results observed in a variety of patients previously treated with ALK inhibitors provides the basis for these applications.”

The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. In April 2017, lorlatinib received Breakthrough Therapy Designation from the FDA for patients with ALK-positive metastatic NSCLC previously treated with one or more ALK inhibitors.

The submissions are based on Phase 2 data from a Phase 1/2 clinical trial (NCT01970865) of lorlatinib, evaluating patients treated in distinct cohorts based on prior therapy. Full results from the Phase 2 portion of the trial were presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in October 2017.

The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in August 2018.

About Lorlatinib

Lorlatinib is an investigational TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.

The Phase 3 CROWN study (NCT03052608) of lorlatinib began enrolling patients earlier this year. CROWN is an ongoing, open label, randomized, two-arm study comparing lorlatinib to crizotinib for treatment-naïve patients with metastatic ALK-positive NSCLC.

Lorlatinib is an investigational agent and has not received regulatory approval anywhere in the world. A multi-center, open-label expanded access protocol (NCT03178071) is now open in the United States for lorlatinib, making it available for eligible adults with ALK-positive or ROS1-positive advanced NSCLC at select sites. More information can be found by visiting www.clinicaltrials.gov.