US regulators are undertaking a speedy review of Novartis' application to expand the use of Zykadia to include its first-line use in patients with ALK positive non small cell lung cancer (NSCLC).
The drug is currently indicated in the second-line setting, that is for patients with ALK positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.
The Swiss drug giant's submission for first-line use is based on primary analysis of ASCEND-4, a global Phase III, randomised, open-label, multicenter clinical trial which evaluated safety and efficacy of the ALK inhibitor compared to platinum-based chemotherapy, including maintenance, in adults with Stage IIIB or IV ALK+ NSCLC.
The findings showed that patients treated with first-line Zykadia had a median progression-free survival (PFS) of 16.6 months compared to 8.1 months for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance.
Also, in a pre-specified analysis of patients receiving Zykadia without brain metastases at screening, patients experienced a median PFS of 26.3 months versus with 8.3 months among those given chemotherapy, while the numbers for patients with brain metastases were 10.7 months and 6.7 months, respectively.
On the safety side, the most common adverse events, occurring in more than 25 percent of Zykadia patients, were diarrhoea (85 percent vs. 11 percent with chemotherapy), nausea (69 percent vs. 55 percent), vomiting (66 percent vs. 36 percent) and an increase in the liver enzymes ALT (60 percent vs. 22 percent) and AST (53 percent vs. 19 percent)
The US Food and Drug Administration also granted Breakthrough Therapy designation to Zykadia for the first-line treatment of patients with ALK+ metastatic NSCLC with metastases to the brain.
The priority review and breakthrough designation "brings us closer to delivering the right treatment to the right patient at the right time," noted Vas Narasimhan, global head of Drug Development and chief medical officer at Novartis.