Completion of Rolling Submission of New Drug Application for Brigatinib to the US FDA

Seeking a marketing approval for patients with metastatic ALK-positive NSCLC who are resistant or intolerant to crizotinib

On 30 August 2016, the ARIAD Pharmaceuticals, Inc. announced that it has completed the rolling submission of the New Drug Application (NDA) for its investigational anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the US Food and Drug Administration (FDA). ARIAD is seeking US marketing approval of brigatinib for patients with metastatic ALK-positive non-small cell lung cancer (NSCLC) who are resistant or intolerant to crizotinib.

The company is seeking accelerated approval for brigatinib from the FDA and has requested a priority review of the application, which, if granted, would allow for approval of brigatinib eight months after the NDA submission, as opposed to 12 months for a standard review.

ARIAD’s NDA submission includes clinical data from its phase I/II and pivotal phase II ALTA trials of brigatinib.

Data from the ALTA trial, in which patients who had experienced disease progression on crizotinib therapy were randomised to one of two brigatinib regimens, were presented at the ASCO 2016 Annual Meeting.

With a median follow-up of 8.3 months, the data show that, for patients treated with the 180 mg regimen with a seven day lead-in at 90 mg (arm B), 54% achieved an investigator-assessed confirmed objective response, the trial’s primary endpoint. In this arm, the median progression-free survival (PFS) exceeded one year (12.9 months). Additionally, a 67% confirmed intracranial objective response rate was achieved in patients with measurable brain metastases.

The most common treatment-emergent adverse events (TEAEs; ≥ 25% of all patients in arm B), regardless of relationship to treatment, were nausea (40%), diarrhoea (38%), cough (34%), increased blood creatine phosphokinase (30%), headache (27%) and fatigue (27%). TEAEs, ≥ grade 3, occurring in ≥ 5% of all patients in arm B, were increased blood creatine phosphokinase (9%), hypertension (6%) and pneumonia (5%). A subset of pulmonary adverse events with early onset (median: day 2; range: day 1-9) occurred in 6% of all patients (≥ grade 3 in 3% of patients); no such events with early onset occurred after dose escalation to 180 mg QD in arm B.

Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK-positive NSCLC whose tumours are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK-positive NSCLC.

ARIAD plans to submit a Marketing Authorization Application (MAA) for brigatinib to the European Medicines Agency (EMA) in early 2017.

The global phase II ALTA trial is the basis for brigatinib’s initial regulatory review. ARIAD has also initiated the phase III ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally-advanced or metastatic ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor.

The press release issued by ARIAD contains forward-looking statements.