ARIAD Pharmaceuticals announced that it has completed the New Drug Application for brigatinib it filed with the U.S. Food and Drug Administration (FDA), seeking market approval to use the treatment in patients with metastatic ALK-positive (ALK+) non-small cell lung cancer (NSCLC) who are resistant or intolerant to crizotinib treatment.
The application for brigatinib was a so-called rolling submission, where the FDA allows a company to submit completed sections for review, rather than waiting until every section is completed before beginning to review the application.
ARIAD is now asking the FDA to speed the review and approval process, making use of an “accelerated approval” program that may be granted to drug candidates targeting serious conditions where there is an unmet treatment need. If granted, the process would reduce the time for a potential approval from 12 to eight months.
“Many patients with ALK-positive non-small cell lung cancer eventually develop disease progression,” Corey Langer, MD, director of thoracic oncology at the Abramson Cancer Center of the University of Pennsylvania and a professor of Hematology-Oncology at the Perelman School of Medicine, said in a news release.
“We are excited that the brigatinib NDA submission is now complete and are hopeful that brigatinib’s data, including the observation of complete responses and activity in the central nervous system, will provide patients and their oncologists with a new treatment option.”
The application builds on data from two clinical trials: a Phase 1/2 trial (NCT01449461) dose-escalation safety study, and a Phase 2 trial (NCT02094573) that studied patients whose cancer progressed during treatment with crizotinib.
Results from the global Phase 2 trial showed that 180 mg brigatinib (starting with seven days of 90 mg) led to a response in 54 percent of patients. Median progression-free survival was 12.9 months. Additionally, among patients with measurable brain metastases, the tumors were seen to respond to treatment in 67 percent of these patients.
Adverse effects occurred in 25 percent of patients in this dose group and were mainly nausea, diarrhea, cough, increased levels of a muscle enzyme, headache, and fatigue. Severe adverse events were only noted in 5 percent of the group, and also included hypertension and pneumonia. Also, some patients (6 percent) experienced lung problems soon after treatment start.
“With the completion of the brigatinib submission this week, we are excited by its potential, if approved, to offer additional hope to patients and their families,” said Paris Panayiotopoulos, president and chief executive officer of ARIAD. “We are thankful to the patients and physicians who participated in the clinical trials of brigatinib.”
ARIAD is currently running two other clinical trials of brigatinib. One is an expanded access study (NCT02784158), enrolling patients who did not meet the criteria for participation in other brigatinib trials. The other is a Phase 3 trial (NCT01449461) comparing the effect of brigatinib to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC, who have not received treatment with an ALK inhibitor before study start. The Phase 3 study is currently recruiting patients and the expanded access may be accepting patients; more information is available by searching under each study’s identifying trial (NCT) number.
ARIAD plans to submit a Marketing Authorization Application for brigatinib to the European Medicines Agency — the regulatory and drug approval agency for the European Union — early next year.