U.S. FDA Approves Takeda’s ALUNBRIG® (brigatinib) as a First-Line Treatment Option for Patients Diagnosed with Rare and Serious Form of Lung Cancer

- Long-Term Results from the Phase 3 ALTA 1L Trial Established ALUNBRIG as a Superior First-Line Treatment Compared to Crizotinib for People with ALK+ Metastatic NSCLC, Including those with Brain Metastases

CAMBRIDGE, MA, USA & OSAKA, Japan I May 22, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) approved ALUNBRIG (brigatinib) for adult patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. This approval expands ALUNBRIG’s current indication to include the first-line setting. ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) designed to target ALK molecular alterations.

“We’re extremely proud of the positive results ALUNBRIG has shown for newly diagnosed ALK+ NSCLC patients, particularly those with brain metastases,” said Teresa Bitetti, President, Global Oncology Business Unit, Takeda. “Through a robust clinical development program and ongoing investigations across the NSCLC treatment landscape, Takeda is committed to uncovering solutions for people living with devastating forms of lung cancer in need of new options. We believe this approval for ALUNBRIG is a substantial step in the right direction and represents significant progress for Takeda’s broader lung cancer portfolio.”

The approval is based on results from the Phase 3 ALTA 1L trial, which is evaluating the safety and efficacy of ALUNBRIG compared to crizotinib in adult patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor.

“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK+ lung cancer patients that have proven to be superior to crizotinib. Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years,” said Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research, University of Colorado Cancer Center. “These data have established brigatinib’s potential in the first-line setting, and I’m confident the FDA approval will open a new window of possibilities for physicians and their patients.”

After more than two years of follow-up, results from the ALTA 1L trial showed ALUNBRIG demonstrated superiority over crizotinib, with significant anti-tumor activity observed, especially in patients with baseline brain metastases.

  • ALUNBRIG reduced the risk of disease progression or death twofold compared with crizotinib (PFS hazard ratio = 0.49), with a 24-month median progression-free survival (PFS) as assessed by a blinded independent review committee (BIRC) versus 11 months for crizotinib.
  • ALUNBRIG demonstrated a confirmed overall response rate (ORR) of 74% (95% CI: 66–81) for ALUNBRIG and 62% (95% CI: 53–70) for crizotinib as assessed by a BIRC.
  • ALUNBRIG demonstrated a confirmed intracranial ORR for patients with measurable brain metastases at baseline of 78% (95% CI: 52–94) for patients treated with ALUNBRIG and 26% (95% CI: 10–48) for patients treated with crizotinib.

“As with many forms of lung cancer, ALK+ NSCLC is a complex and aggressive cancer that presents various treatment challenges for patients who are newly diagnosed, including those whose disease has spread to their brain,” said Andrea Stern Ferris, President and CEO, LUNGevity Foundation. “Having this option for newly diagnosed patients is exciting news for the ALK+ NSCLC community and adds to the remarkable progress we have witnessed in lung cancer treatment over the past decade.”

About the ALTA 1L Trial

The Phase 3 ALTA 1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial of ALUNBRIG in adults is a global, ongoing, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients (ALUNBRIG, n=137, crizotinib, n=138) with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Patients received either ALUNBRIG, 180 mg orally once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg orally twice daily.

The median age was 58 years in the ALUNBRIG arm and 60 years in the crizotinib arm. Twenty-nine percent of patients had brain metastases at baseline in the ALUNBRIG arm versus 30% in the crizotinib arm. Twenty-six percent of patients received prior chemotherapy for advanced or metastatic disease in the ALUNBRIG arm versus 27% in the crizotinib arm.

Blinded independent review committee (BIRC)-assessed progression-free survival (PFS) was the major efficacy outcome measure. Additional efficacy outcome measures included confirmed overall response rate (ORR) per RECIST v1.1 and intracranial ORR.

The warnings and precautions for ALUNBRIG are: interstitial lung disease (ILD)/pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation, hyperglycemia and embryo-fetal toxicity.

In the ALTA 1L trial, serious adverse reactions occurred in 33% of patients receiving ALUNBRIG. The most common serious adverse reactions other than disease progression were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions other than disease progression occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

The most common adverse reactions in the ALTA 1L trial (≥10%) with ALUNBRIG were diarrhea (53%), rash (40%), cough (35%), hypertension (32%), fatigue (32%), nausea (30%), myalgia (28%), dyspnea (25%), abdominal pain (24%), and headache (22%). 

About ALUNBRIG® (brigatinib)

ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target anaplastic lymphoma kinase (ALK) molecular alterations.

ALUNBRIG is currently approved in more than 40 countries, including the U.S., Canada and the European Union (EU), for the treatment of people living with ALK+ metastatic NSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib. ALUNBRIG is also approved in the EU as a monotherapy for the treatment of adult patients with ALK+ advanced NSCLC previously not treated with an ALK inhibitor.

ALUNBRIG 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+ NSCLC, ROS1+ and EGFR+ NSCLC.

About ALK+ NSCLC

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.1,2 Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients.3 Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.4,5,6

Takeda is committed to continuing research and development in NSCLC to improve the lives of the approximately 40,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year.7

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.

For more information, visit https://www.takeda.com.

1 World Health Organization. Latest Global Cancer Data. https://www.who.int/cancer/PRGlobocanFinal.pdf. Accessed May 11, 2019.

2 American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed May 11, 2019.

3 Kris MG, et al. JAMA, 2014;311:1998-2006.

4 Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-81.

5 Koivunen JP, Mermel C, Zejnullahu K, et al. Clin Cancer Res. 2008; 14(13):4275-83.

6 Wong DW, Leung EL, So KK, et al. Cancer. 2009; 115(8):1723-33.

7 Chia PL, Mitchell P, Dobrovic A, John T. Clin Epidemiol, 2014;6:423-432.

SOURCE: Takeda Pharmaceutical Co

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