EMA recommends approval for advanced lung cancer agent ceritinib

The European Medicines Agency (EMA) has recommended granting a conditional marketing authorisation for ceritinib (Zykadia), for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in adults with advanced disease that have already been treated with crizotinib. 

The EMA recommendation for ceritinib is conditional on the manufacturer, Novartis, providing further results from ongoing studies and a comparative phase III study within three years. The evidence so far is based on two uncontrolled studies. In support of its conditional recommendation, the EMA cited a “high unmet need” for the drug. 

Ceritinib, a protein kinase inhibitor, acts by inhibiting autophosphorylation of ALK, ALK mediated phosphorylation of downstream signalling proteins and proliferation of ALK dependent cancer cells. ALK-positive cases are those where the NSCLC cells contain defects in the gene responsible for the protein anaplastic lymphoma kinase, thereby aiding cancer proliferation. 

Crizotinib, a tyrosine kinase inhibitor, is currently used to manage locally advanced or metastatic ALK-positive NSCLC (and is the only drug currently approved for this), but disease progression is common and not all patients respond to this drug. 

The most common side effects for ceritinib included diarrhoea, nausea, vomiting, fatigue, liver test abnormalities, abdominal pain, oesophageal disorder and anaemia. The most serious adverse reactions included hepatotoxicity, QT interval prolongation, bradycardia and hyperglycaemia, according to the EMA. 

Around 85% of all lung cancers are NSCLC. Of these, 2–7% are ALK-positive cases.  

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Citation
The Pharmaceutical Journal, PJ, 14 March 2015, Vol 294, No 7853;294(7853):DOI:10.1211/PJ.2015.20068053