The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to Genentech’s anaplastic lymphoma kinase (ALK) inhibitor Alecensa (alectinib) for the treatment of adults with ALK-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor. This adds to the FDA’s June 2013 BTD that was granted to Alecensa to treat ALK-positive NSCLC patients who progressed on treatment with Xalkori (crizotinib), another ALK inhibitor.
Breakthrough Therapy is an FDA designation that is meant to expedite the development and review of drug candidates that show promise in treating life-threatening diseases, offering substantial treatment advantages beyond existing options.
The designation was supported by recent data from the J-ALEX study, a randomized, open-label, Phase 3 trial that evaluated the efficacy of Alecensa versus Xalkori in Japanese patients with ALK-positive, advanced or recurrent NSCLC, who had not received any prior ALK inhibitor.
The study, which enrolled 207 participants, showed that compared to Xalkori, Alecensa reduced the risk of disease progression or death by 66%, and had fewer serious adverse events (27% vs. 51%). The most common side effect of Alecensa was constipation, which was seen in 36% of patients, while among those taking Xalkori, 74% had nausea, 73% diarrhea, 59% vomiting, 55% visual problems, 52% alteration in taste, and 46% constipation. Elevation of liver enzymes also was observed in more than 30% of patients taking Xalkori.
In addition, although median progression-free survival (PFS) was not reached for Alecensa, at the time of analysis it was more than double that observed in patients taking Xalkori.
“The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease,” Sandra Horning, MD, chief medical officer and head of Global Product Development, said in a press release. “The decision by the FDA to grant a second Breakthrough Therapy Designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor,” she said.
Alecensa recently was granted Accelerated Approval for the treatment of patients with ALK-positive NSCLC who progressed on, or are intolerant to, Xalkori, allowing the drug to be approved based on a surrogate endpoint, which will expedite the approval process.
Now, the ongoing ALEX study (NCT02075840), a global, randomized, Phase 3 trial that is evaluating Alecensa vs. Xalkori as a first-line therapy in patients with ALK-positive NSCLC, is expected to convert the initial Accelerated Approval for patients with ALK-positive, metastatic NSCLC, to a full approval as an initial treatment.