On February 6, 2017 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported the submission of a Marketing Authorization Application (MAA) for its investigational oral anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the European Medicines Agency (EMA) (Press release, Ariad, FEB 6, 2017, View Source;p=RssLanding&cat=news&id=2243225 [SID1234517645]). 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 U.S. Food and Drug Administration (FDA) is currently reviewing a New Drug Application for brigatinib filed by ARIAD and has set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA).
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"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 U.S. 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, MD, 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 percent 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 percent (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.
About Brigatinib
Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD. It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC). The global Phase 2 ALTA trial, in patients with locally advanced or metastatic ALK+ NSCLC who were previously treated with crizotinib, is the primary basis for brigatinib’s initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor. More information on brigatinib clinical trials can be found here.
Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted Orphan Drug designation by the FDA for the treatment of ALK+, ROS1+ and EGFR+ NSCLC.
About ALK+ NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80 to 85 percent of the estimated 222,500 new cases of lung cancer diagnosed each year in the United States, according to the American Cancer Society. Anaplastic lymphoma kinase (ALK) was first identified as a chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL). Genetic studies indicate that chromosomal rearrangements in ALK are key drivers in a subset of NSCLC patients as well. Approximately five percent of patients with NSCLC have a rearrangement in the ALK gene, according to the American Cancer Society.