Ariad Pharmaceuticals has completed its rolling submission of a new drug application (NDA) for brigatinib, an investigational anaplastic lymphoma kinase (ALK) inhibitor. The company is seeking marketing approval of brigatinib from the FDA for the treatment of patients with metastatic ALK-positive (ALK+) non–small-cell lung cancer (NSCLC) who are resistant to or intolerant of crizotinib (Xalkori, Pfizer/EMD Serono). The company has also requested priority review of the application, which, if granted, would allow the approval of brigatinib eight months after the NDA submission, as opposed to 12 months for a standard review.
The NDA submission includes clinical data from the pivotal phase 2 ALTA trial, in which patients who had experienced disease progression during crizotinib therapy were randomly assigned to one of two brigatinib regimens. With a median follow-up period of 8.3 months, the data showed that, for patients treated with the 180-mg regimen with a seven-day lead-in at 90 mg (arm B), 54% achieved a confirmed objective response, the trial’s primary endpoint. In this arm, median progression-free survival was 12.9 months. In addition, a confirmed intracranial objective response rate of 67% was achieved in patients with measurable brain metastases.
The most common treatment-emergent adverse events (TEAEs) greater than or equal to 25% of all patients in arm B, regardless of relationship to treatment, included nausea (40%), diarrhea (38%), cough (34%), increased blood creatine phosphokinase (30%), headache (27%), and fatigue (27%). TEAEs greater than or equal to grade 3 included increased blood creatine phosphokinase (9%), hypertension (6%), and pneumonia (5%). A subset of pulmonary adverse events with early onset (median: day 2; range: days 1 to 9) occurred in 6% of all patients (greater than or equal to grade 3 in 3% of patients) in arm B; no such events with early onset occurred after dose escalation to 180 mg once daily.
Source: Ariad Pharmaceuticals; August 30, 2016.