Genentech, a member of the Roche Group announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for Alecensa (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. The approval is based on results from the Phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 47 percent (HR=0.53, 95 percent CI: 0.38, 0.73, p<0.0001) compared to crizotinib as assessed by independent review committee (IRC). Median PFS was 25.7 months (95 percent CI: 19.9, not estimable) for people who received Alecensa compared with 10.4 months (95 percent CI: 7.7, 14.6) for people who received crizotinib. The safety profile of Alecensa was consistent with that observed in previous studies.
The study also showed that Alecensa significantly reduced the risk of the cancer spreading to or growing in the brain or central nervous system (CNS) compared to crizotinib by 84 percent (HR=0.16, 95 percent CI: 0.10, 0.28, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12 percent) compared to people who received crizotinib (45 percent).
“Our goal is to develop medicines that have the potential to significantly improve upon the standard of care,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “In our pivotal study, Alecensa significantly extended the time that people lived without their disease worsening compared to crizotinib and also showed a marked reduction in the risk of their cancer spreading to the brain.”
“ALK-positive lung cancer is often found in younger people, who tend to have more advanced disease at the time of diagnosis, and comes with a unique set of challenges," said Bonnie J. Addario, a lung cancer survivor and founder of the Bonnie J. Addario Lung Cancer Foundation (ALCF). “We applaud advancements in care, like the approval of Alecensa, which provides a new initial treatment option for people with this type of lung cancer.”
Alecensa received Breakthrough Therapy Designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Results from the Phase III ALEX study were simultaneously presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Subsequently, Alecensa was recommended in the National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for first-line ALK-positive metastatic NSCLC (Category 1, Preferred).
In addition to today’s approval, the FDA also converted Alecensa’s initial accelerated approval in December 2015 for the treatment of people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib (second-line) to a full approval.
About the ALEX study
ALEX (NCT02075840/B028984) is an open-label, randomized, active-controlled, multicenter, Phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in people with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease and whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, an immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomized (1:1) to receive either Alecensa or crizotinib. The major efficacy outcome measure of the ALEX study is PFS according to RECIST v1.1 as determined by investigator assessment. Additional efficacy outcome measures include: PFS as determined by IRC, time to CNS progression by IRC based on RECIST v1.1, objective response rate (ORR) and duration of response (DOR), and overall survival (OS). Additional exploratory outcome measures were CNS-ORR and CNS-DOR by IRC in people with measurable CNS metastases at baseline. The multicenter study was conducted in 303 people across 161 sites in 31 countries. OS data are currently considered immature with only about a quarter of events being reported.
Grade ≥ 3 adverse reactions were reported for 41 percent of people treated with Alecensa. The most common Grade 3-4 adverse reactions (≥ 3 percent) were evidence of kidney dysfunction (increased creatinine; 4.1 percent), evidence of liver dysfunction (hyperbilirubinemia; 5 percent), low levels of sodium (hyponatremia; 6 percent), increased liver enzymes (aspartate transaminase; 6 percent, and alanine transaminase; 6 percent), and decreased red blood cells (anemia; 7 percent). Serious adverse reactions reported in ≥ 2 percent of people treated with Alecensa were pneumonia (4.6 percent) and renal impairment (3.9 percent).
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