The European Commission has conditionally authorized F. Hoffmann-La Roche to market the ALK inhibitor Alecensa (alectinib hydrochloride) for treatment of patients with ALK-positive, metastatic non-small cell lung cancer (NSCLC) who are intolerant or progressed on Xalkori (crizotinib) treatment.
An estimated 5 percent of NSCLC patients have a chromosomal rearrangement in which the ALK gene is fused with another gene and becomes overactivated, transformating them into tumor cells and uncontrolled growth.
Alecensa is a selective ALK inhibitor designed for patients with these chromosomal rearrangements, holding promise in the treatment of brain metastasis as it is not recognized by the brain efflux system that pumps molecules out of the brain.
In December, 2015, the U.S. Food and Drug Administration approved Alecensa, developed by Japan’s Chugai to treat people with advanced ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, another ALK inhibitor called Xalkori. Canada, Hong Kong, India, Israel, Kuwait, Switzerland and South Korea have also approved the drug.
“In July 2014, Japan became the first country in the world to receive regulatory approval,” Dr. Yasushi Ito, Chugai’s senior vice president, said in a news release. “We believe that approval of Alecensa by the European Commission will bring great hope for patients in the European Union living with this disease.”
The European marketing authorization was based on data from two Phase 1/2 trials. The NP28761 study (NCT01871805) is a single arm, open-label, multi-center trial designed to assess the safety and efficacy of Alecensa in 87 ALK-positive NSCLC patients who had received prior Xalkori treatment. Alecensa (600 mg) was administered orally twice daily.
By the time of data cutoff, in October 2014, the objective response rate was 52.2 percent, including full and partial responses, as assessed by an independent review committee. The median duration of response was 14.9 months and patients took a median of eight months until disease progression.
The NP28673 study (NCT01801111) is a global, single-arm, open-label, multi-center trial evaluating the safety and efficacy of Alecensa in 138 NSCLC patients with ALK rearrangements, who progressed on Xalkori.
At the time of data cutoff in January 2015, 50.8 percent of patients had achieved a full or a partial response to Alecensa. Median duration of response was 15.2 months, and median progression-free survival was 8.9 months.
The researchers reported a safety profile that was consistent with that observed in prior Alecensa studies, with the most common Grade 3 or higher adverse events including increase in muscle and liver enzymes and shortness of breath.