Ariad Pharmaceuticals has announced the submission of a Marketing Authorization Application (MAA) for its investigational oral anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the European Medicines Agency (EMA). Ariad is seeking marketing approval in the European Union of brigatinib in adult patients with anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) who have been previously treated with crizotinib. The US Food and Drug Administration (FDA) is currently reviewing a New Drug Application (NDA) for brigatinib filed by Ariad and has set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA).

“Ariad's submission of the brigatinib MAA to the EMA is one of many recent milestones highlighting our strong investment in internally discovered rare cancer therapies,” said Paris Panayiotopoulos, president and chief executive officer of Ariad. “Since announcing our definitive agreement to combine with Takeda, we remain focused on our accountability to our patients by propelling brigatinib forward and by preparing for its anticipated US launch.”

“The brigatinib clinical trials have provided patients with refractory ALK+ NSCLC, including those patients who have metastatic brain lesions, with a potential important treatment option,” said Maurice Perol, managing director, Léon Bérard Cancer Center, Lyon, France. “Based on the clinical data we’ve seen to date, we are really excited by the prospect that appropriate patients in the EU may have access to brigatinib as a new targeted treatment.”

Ariad’s MAA submission includes clinical data from its phase 1/2 and pivotal phase 2 ALTA trials of brigatinib. Results from the ALTA trial and central nervous system (CNS) activity in the ALTA and phase 1/2 trials were reported at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) in December 2016. In the ALTA trial, 222 patients received either 90 mg of brigatinib once per day (QD) continuously or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days. Data from the ALTA trial demonstrated that of 110 patients on the 180-mg regimen QD with a seven-day lead-in at 90 mg QD with a median follow-up of 11.0 months, 55 per cent achieved confirmed objective response as assessed by the investigator. In this arm, the median progression-free survival (PFS) was 15.6 months in this post-crizotinib setting, by both investigator and independent review committee (IRC) assessment.

Additionally, in this arm, 67 per cent (12/18) of patients with measurable brain metastases achieved a confirmed intracranial objective response. The most common treatment-emergent adverse events (TEAEs; = 25% of all patients in this arm, regardless of relationship to treatment), were nausea (43%), fatigue (40%), diarrhea (39%), cough (36%), increased blood creatine phosphokinase (CPK) (33%), headache (30%), rash (28%), and vomiting (26%). The most common serious adverse reactions other than neoplasm progression reported in 2% or more of patients included pneumonia (5.0%), pneumonitis (5.0%) and epilepsy (2.3%). A subset of pulmonary adverse events (AEs) with early onset (median: Day 2; range: Day 1-9) occurred in 6.4 percent of all patients (grade =3 in 3% of patients); no such events with early onset occurred after dose escalation to 180 mg QD following the lead-in dose of 90 mg for seven days.