Takeda Pharmaceutical Company Limited announced that the European Commission (EC) extended the current marketing authorization of ALUNBRIG (brigatinib) to include use as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. This decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on February 27, 2020.
“Patients with ALK+ NSCLC, particularly those who have developed brain metastases, have been in need of additional treatment options that are proven effective in the first-line setting,” said Professor Sanjay Popat, Consultant Medical Oncologist, Royal Marsden NHS Foundation Trust. “As brigatinib has shown superiority compared to crizotinib in this setting, including in patients whose disease has spread to the brain, this approval is an important advancement for these patients and gives physicians in the European Union another choice when addressing the needs of ALK+ NSCLC patients.”
“At Takeda, our commitment to patients drives us as we seek to advance care and address the unmet needs of the lung cancer community,” said Teresa Bitetti, President, Global Oncology Business Unit, Takeda. “We are proud of the positive results ALUNBRIG has demonstrated in the first-line setting, including strong overall and intracranial efficacy, and look forward to making ALUNBRIG available to newly diagnosed ALK+ NSCLC patients in Europe.”
“ALK+ NSCLC is a complex and nuanced disease, and people with this form of lung cancer may benefit from the availability of a variety of treatment options,” said Stefania Vallone, President of Lung Cancer Europe (LUCE). “We welcome the availability of additional treatment options that may benefit the European cancer community and patients with this serious and rare form of the disease, with the hope that they will soon be accessible to patients across Europe.”
The approval is based on results from the Phase 3 ALTA-1L trial, which evaluated the safety and efficacy of ALUNBRIG compared to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Results from the trial showed ALUNBRIG demonstrated superiority compared to crizotinib with significant anti-tumor activity observed in patients with baseline brain metastases. After more than two years of follow-up, ALUNBRIG reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (hazard ratio [HR] = 0.31, 95% CI: 0.17–0.56), as assessed by a blinded independent review committee (BIRC), and reduced the risk of disease progression or death by 76% in patients with brain metastases at baseline (HR = 0.24, 95% CI: 0.12–0.45), as assessed by investigators. ALUNBRIG also demonstrated consistent overall efficacy (intent to treat population), with a median progression-free survival (PFS) more than two times longer than that with crizotinib at 24.0 months (95% CI: 18.5–NE) versus 11.0 months (95% CI: 9.2–12.9) for crizotinib, as assessed by BIRC, and 29.4 months (95% CI: 21.2–NE) versus 9.2 months (95% CI: 7.4–12.9), as assessed by investigators.
The safety profile of ALUNBRIG in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC). The most common treatment-emergent adverse events (TEAEs) Grade ≥3 in the ALUNBRIG arm were increased CPK (24.3%), increased lipase (14.0%) and hypertension (11.8%); and for crizotinib were increased ALT (10.2%), AST (6.6%) and lipase (6.6%).
This decision by the European Medicines Agency means that ALUNBRIG is now approved for marketing of this indication in all European Union member states, in addition to Norway, Liechtenstein and Iceland.