Pfizer’s Third-Generation ALK Inhibitor Lorlatinib Granted Priority Review Designation by the FDA

Release date: 2026-01-23 13:12:04     Recommended: 13

Pfizer Inc. recently announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) for lorlatinib (brand name: Lorbrena), a third-generation anaplastic lymphoma kinase (ALK) inhibitor, for the first-line treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). Concurrently, the FDA has granted priority review designation to this sNDA and is evaluating it under the Real-Time Oncology Review (RTOR) pilot program, with a decision expected by April 2021.

Lorbrena is a tyrosine kinase inhibitor (TKI) that has demonstrated high activity in preclinical lung cancer models harboring ALK rearrangements. Specifically developed to inhibit ALK gene mutations resistant to other ALK inhibitors, Lorbrena is also capable of crossing the blood-brain barrier to treat brain metastases. Brain metastases occur in up to 40% of patients with ALK-positive lung cancer.

Lung cancer is among the leading causes of cancer-related deaths worldwide. NSCLC accounts for approximately 80–85% of all lung cancer cases, and ALK-positive tumors are identified in roughly 3–5% of NSCLC patients.

This sNDA is supported by positive results from the phase 3 CROWN clinical trial. Mid-term analysis findings, published in the New England Journal of Medicine this November, showed that compared with crizotinib—the current first-line standard of care—lorlatinib reduced the risk of disease progression or death by 72% (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.19–0.41; P<0.001). The median progression-free survival (PFS) was 9.3 months in the crizotinib group, whereas the median PFS in the lorlatinib group had not been reached at the time of analysis.

Lorlatinib also exhibited significant advantages in the prevention and alleviation of brain metastases. At 12 months, the rate of intracranial progression-free survival was 96% in the lorlatinib group, compared with 60% in the crizotinib group. Lorlatinib reduced the risk of intracranial disease progression or death by 93%!

“The FDA’s decision to evaluate lorlatinib’s regulatory submission through innovative review pathways designed to expedite the review process highlights its potential as an initial treatment option for patients with ALK-positive advanced NSCLC,” stated Dr. Chris Boshoff, Chief Development Officer, Oncology, Pfizer Global Product Development. “We look forward to collaborating with the FDA to bring this treatment option to patients as soon as possible.”