On October 2, 2014 ARIAD Pharmaceuticals reported that its investigational cancer medicine, AP26113, has received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who are resistant to crizotinib (Press release Ariad, OCT 2, 2014, View Source [SID:1234500777]). This designation is based on results from the ongoing Phase 1/2 trial (NCT02094573) that show sustained anti-tumor activity of AP26113 in patients with ALK+ NSCLC, including patients with active brain metastases.

“We are very pleased that the FDA has granted Breakthrough Therapy designation to AP26113,” stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. “We are encouraged by the clinical data on AP26113 that were presented recently at the European Cancer Congress, particularly in patients whose tumor had spread to the brain. We are focused on accelerating patient enrollment in the ongoing ALTA trial and on planning a front-line trial of AP26113 in treatment-naive patients.”

Phase 1/2 Data

Updated clinical data from the Phase 1/2 trial of AP26113 were recently shared at the 2014 European Cancer Congress. A total of 137 patients have been enrolled in the trial in the United States and Europe. Objective responses were observed in ALK+ NSCLC patients, and responses were observed in patients who were either TKI-naïve or resistant to crizotinib. Of the 72 ALK+ NSCLC patients evaluable for response, 52 (72%) demonstrated an objective response. The median duration of response was 49 weeks, and the median progression-free survival (PFS) was 56 weeks. In a subgroup analysis, 10 of 14 (71%) ALK+ NSCLC patients with active, untreated or progressing, brain metastases had evidence of radiographic improvement in those metastases. Of the seven evaluable TKI-naïve ALK+ NSCLC patients treated with AP26113, all demonstrated an objective response, including two complete responses (CR).

The most common adverse events (AEs), regardless of treatment relationship and including all grades, were nausea (45%), diarrhea (37%), and fatigue (37%). Adverse events, grade 3 or higher, occurring in three or more patients were dyspnea (4%), increased lipase (4%), hypoxia (4%), fatigue (3%), alanine aminotransferase (ALT) increased (2%) and amylase increased (2%). Serious AEs, all causality, occurring in three or more patients were dyspnea (7%), pneumonia (5%), hypoxia (4%), neoplasm progression (4%), pyrexia (2%) and pulmonary embolism (2%).

The 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) established the Breakthrough Therapy designation to expedite the development and review of new drugs with preliminary clinical evidence demonstrating that they may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. The Breakthrough Therapy designation is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met. As of September 3, 2014, FDA listed 213 total requests for Breakthrough Designation, and 61 requests were granted. Approximately 41% of the designated products are in cancer. (View Source).