Novartis seeks expanded indication of ceritinib (Zykadia) in the European Union.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recently recommended expanding the indication of ceritinib (Zykadia) to include the treatment of patients with advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC).
If approved in the European Union, ceritinib would provide a new treatment option for newly-diagnosed and treatment-naïve patients with ALK-positive advanced NSCLC, according to a press release.
The CHMP opinion was based on positive findings from the phase 3 ASCEND-4 clinical trial, which studied the efficacy of ceritinib compared with chemotherapy. Included in the clinical trial were 376 patients with stage 3b or 4 ALK-positive NSCLC who were not previously administered treatment.
Patients were randomized to receive ceritinib 750-mg/day or pemetrexed-based platinum doublet chemotherapy for 4 cycles followed by pemetrexed maintenance, according to Novartis.
The investigators found that patients receiving ceritinib experienced a 45% reduction in disease progression compared with chemotherapy-treated patients, according to the release. For individuals treated with ceritinib, the median progression-free survival was 16.6 months, while it was only 8.1 months for patients treated with chemotherapy.
Patients without brain metastases treated with ceritinib experienced progression-free survival of 26.3 months compared with only 8.3 months for patients treated with chemotherapy.
For patients with brain metastases, treatment with ceritinib was associated with a median progression-free survival of 10.7 months. Patients in the chemotherapy treatment arm had progression-free survival of 6.7 months, according to the study.
Approximately 59% of patients with brain metastases did not receive prior brain radiotherapy. The authors noted that the high intracranial overall response rate of 72.7% was consistent with the whole body response rate.
The most common adverse events occurring in more than one-quarter of patients treated with ceritinib included diarrhea, nausea, vomiting, ALT increase, AST increase, GGT increase, decreased appetite, blood alkaline phosphate increase, and fatigue, according to the release.
The positive CHMP recommendation will be reviewed by the European Commission, which typically follows the recommendation and approves drugs within 2 months. If approved, patients in all 28 European Union member states plus Iceland, Lichtenstein, and Norway will have access to the treatment, Novartis reported.
Earlier this year, the FDA granted ceritinib breakthrough designation for the treatment of patients with ALK-positive NSCLC with brain metastases. The application is currently under priority review. In the United States, Zykadia has been approved to treat patients with ALK+ metastatic NSCLC who have progressed on, or are tolerant to crizotinib.
"Novartis is committed to bringing targeted treatment options to more patients living with lung cancer who may benefit from them," said Bruno Strigini, CEO, Novartis Oncology. "Today, we've taken an important step towards fulfilling that commitment with the potential approval of Zykadia as a first-line treatment option for those in the EU diagnosed with ALK-positive advanced NSCLC."