Priority Review Granted for ALK-Positive Lung Cancer Drug

Today, Roche announced that the FDA has accepted the supplemental new drug application (sNDA) for alectinib (Alcensa) as a first-line therapy for patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC). The FDA also granted the application priority review designation, according to a press release.

Roche reports that the FDA will make their final decision by November 30, 2017.

“Phase III results showed Alecensa reduced the risk of disease worsening by more than half compared to the current standard of care and lowered the risk of tumours [sic] spreading to or growing in the brain by more than 80%,” said Sandra Horning, MD, chief medical officer and head of Global Product Development for Roche and Genentech. “We are working closely with the FDA to bring this medicine as an initial treatment for people with ALK-positive NSCLC as soon as possible.”

The sNDA for alectinib was based on positive results from a pair of phase 3 clinical trials, ALEX and J-ALEX. Roche reported that the ALEX study sought to translate accelerated approval of the drug to a full approval.

ALEX

Included in the ALEX study were 303 treatment-naïve patients with ALK-positive NSCLC whose tumors were characterized as ALK-positive by the Ventana Alk (D5F3) CDx Assay, according to the release. Patients were randomized to receive alectinib or crizotinib.

The investigators found that alectinib dropped the risk of progression-free survival (PFS) by 53% compared with crizotinib, according to the study. Median PFS was 25.7 months among alectinib-treated patients versus 10.4 months in crizotinib-treated patients.

Alectinib was also observed to lower the risk of progression in the central nervous system (CNS) by 84% compared with crizotinib. Significantly, the investigators found that the 12-month rate of CNS progression for all patients was 9.4% for those treated with alectinib, while it was 41.4 % for those treated with crizotinib, according to the release.

Serious adverse events were less common among patients treated with alectinib. The most common grade 3 to 5 adverse events included high liver enzymes and decreased red blood cells.

J-ALEX

Included in the study were 207 patients with ALK-positive, advanced or recurrent NSCLC who have not received prior treatment with an ALK inhibitor. Patients were randomized to receive alectinib or crizotinib.

The investigators discovered that alectinib reduced PFS by 62% compared with crizotinib. Median PFS for alectinib was 25.9 months compared with 10.2 months for crizotinib.

Alectinib also reduced the risk of progression in the CNS by 81% in patients without baseline brain metastases, and by 49% among those with baseline metastases, according to the study.

Serious adverse events were observed less frequently in the alectinib treatment arm. The most common grade 3 to 4 adverse events in the alectinib arm were increased muscle enzymes and interstitial lung disease.

Alectinib received accelerated approval in December 2015 for patients with ALK-positive metastatic NSCLC who have progressed on, or are intolerant to, crizotinib.

Alectinib was granted breakthrough therapy designation in September 2016 for the treatment of patients with advanced ALK-positive NSCLC who have not been previously treated with an ALK inhibitor. This designation was granted based on the results from J-ALEX, according to the release.

Additionally, the European Medicines Agency validated the new indication in these patients based on the phase 3 clinical trial results, according to the press release.