According to a release on Biospace, the European Commission (EC) has approved Takeda Pharmaceutical’s ALUNBRIG (brigatinib) as treatment for patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) who were not treated by any ALK inhibitor in the past.
About Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer
Non-small cell lung cancer is a common form of cancer that makes up about 80-85% of lung cancer cases. Most typically, NSCLC presents as adenocarcinoma, large cell carcinoma, or squamous cell carcinoma.
However, an article published in Targeted Oncology states that only 3-7% of NSCLC cases result from mutations or rearrangements in the anaplastic lymphoma kinase genes. If this gene overproduces protein, it can lead to tumor development. Read the full article here.
So, anaplastic lymphoma kinase-positive NSCLC is a type of lung cancer caused by ALK genetic mutations. About 40,000 people worldwide are diagnosed with ALK+ NSCLC each year. Symptoms include chest pain, fatigue, a lasting cough, jaundice, and weight loss. Some patients, as the disease progresses, may also experience malignant brain tumors.
Takeda & the Treatment of Anaplastic Lymphoma Kinase+ NSCLC
One of Takeda’s main goals is to address unmet needs in oncology. They are currently completing a number of trials on TAK-788, an EGFR/HER2 inhibitor, for the treatment of patients with NSCLC.
In addition to the Phase 3 ALTA trial, Takeda’s programs for ALUNBRIG include:
- Phase 1/2 trial to understand safety, anti-tumor activity, and tolerability
- Phase 2 J-ALTA for Japanese patients previously treated with Alectinib
- Pivotal Phase 2 ALTA trial to determine safety and efficacy during two dosing regimens for patients who had previously been treated with crizotinib
- Phase 2 ALTA 2 to evaluate the impact of ALUNBRIG for patients previously treated with Alectinib or ceritinib
- Phase 3 ALTA 3 to test the safety and efficacy of ALUNBRIG and Alectinib for patients who had previously taken crizotinib
ALUNBRIG Approval
Prior to this approval, ALUNBRIG received Accelerated Approval in 2017 from the U.S. Food and Drug Administration to treat patients with anaplastic lymphoma kinase-positive NSCLC who were not responding to crizotinib treatment. It was also given a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on February 27, 2020.
Its current approval follows positive Phase 3 ALTA-1L trial results. ALUNBRIG was shown to be more effective than crizotinib as a first-line therapy.
What is ALUNBRIG?
ALUNBRIG is a tyrosine kinase inhibitor (TKI) therapy used to impede anaplastic lymphoma kinase genetic mutations. Tyrosine kinases are a type of enzyme that are often found at increased levels in cancer cells. By targeting tyrosine kinases, researchers can prevent the growth of malignant cells. TKIs are frequently used in oncology.
ALUNBRIG is approved in over 40 countries. It has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for the treatment of patients with ALK+ NSCLC, as well as Orphan Drug Designation for the treatment of ALK+ NSCLC, ROS1+ NSCLC, and EGFR+ NSCLC.
Phase 3 ALTA-1L Trial
This randomized, open-label, multi-center trial followed 275 patients with anaplastic lymphoma kinase-positive NSCLC who had not received prior ALK inhibitor treatment. During ALTA-1L, patients were split into two groups.
Group One
Group one had a median age of 58 years. They received 180 mg ALUNBRIG once daily following a one-week period receiving 90 mg once daily. 29% of patients had brain tumors, and 26% of patients previously received chemotherapy.
Group Two
Group two had a median age of 60 years. They received 250 mg of crizotinib, a targeted chemotherapy drug, twice daily. As compared to Group 1, 30% of Group 2 patients had brain tumors. Finally, 27% previously received chemotherapy.
Results
Researchers found that ALUNBRIG was both safe and effective for patients with anaplastic lymphoma kinase-positive NSCLC. Comparatively, it performed better than crizotinib, particularly in anti-tumor activity.
After two years of follow-up, researchers discovered that ALUNBRIG reduced the rate of disease progression and death by between 69-76% for patients with brain tumors.
Patients treated with ALUNBRIG were also shown to have less disease progression than those treated with crizotinib. ALUNBRIG prevented disease progression for between 24 and 29.4 months, with crizotinib coming in at 9.2 to 11 months.
However, the study also found that certain populations should not be treated with ALUNBRIG. This includes patients who are pregnant or breastfeeding as well as elderly or pediatric patients.
Adverse effects include hypertension, increased lipase, increase CPK and AST, anemia, diarrhea, nausea, fatigue, muscle aches, shortness of breath, and increased insulin levels. Only 2% of patients had extreme adverse effects resulting in pneumonia, pneumonitis, or extreme shortness of breath. These usually occurred within 7 days of treatment.
