Novartis lung cancer drug Zykadia approved

Novartis has gained US approved for Zykadia, its new targeted lung cancer drug.

Zykadia (ceritinib, previously known as LDK378) is for patients with the ALK+ mutation (anaplastic lymphoma kinase-positive) sub-type of metastatic non-small cell lung cancer who have progressed on or are intolerant to Pfizer's Xalkori (crizotinib).

Pfizer's drug, launched in 2011, was the first drug to target non-small cell lung cancer (NSCLC) patients with ALK+ tumours, but patients given the drug will eventually see their tumour develop resistance to the treatment.

"Zykadia represents an important treatment option for ALK+ NSCLC patients who relapse after starting initial therapy with crizotinib," said lead investigator Alice T. Shaw, MD, PhD, Massachusetts General Hospital Cancer Center, Boston. "This approval will affect the way we manage and monitor patients with this type of lung cancer, as we will now be able to offer them the opportunity for continued treatment response with a new ALK inhibitor."

Patients with the ALK+ gene account for only 2-7% of NSCLC cases, and the mutation must be diagnosed with a molecular test before treatment can begin.

The approval of Zykadia is based on a pivotal trial that included 163 patients with metastatic ALK+ NSCLC who progressed on or were intolerant to treatment with crizotinib. The most common sites of metastases in the patient population studied were brain (60%), liver (42%) and bone (42%).

Among previously-treated patients, Zykadia achieved an overall response rate (ORR) in just over half of patients (54.6%) and a median duration of response (DOR) of 7.4 months.

The drug hasn't yet produced any mature overall survival (OS) data, which it will have to demonstrate in order to gain traction in the long term.

Analysts aren't yet convinced Zykadia can overtake Xalkori - forecasts put its annual sales in 2018 at around $329 million, far behind the $830 million predicted for Pfizer's drug. In order to overhaul Xalkori, Novartis' drug will have to show superiority in second or first line treatment.

Breakthrough Therapy designation

Zykadia is one of the first medicines to be approved following FDA Breakthrough Therapy designation, which was received in March 2013 due to the significance of results observed in the pivotal trial and the serious and life-threatening nature of ALK+ NSCLC. Additional regulatory submissions for Zykadia are underway worldwide, with an application currently filed in the European Union.

"The approval of Zykadia less than three and a half years after the first patient entered our clinical trial exemplifies what is possible with a highly focused approach to drug development and strong collaboration," said Alessandro Riva, MD, President, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. "The dedication of clinical investigators, patients, the FDA and others has enabled us to bring this medicine to patients in need as swiftly as possible."

Novartis has an ongoing clinical trial programme in this patient population. Several major studies evaluating treatment with ceritinib are being conducted in more than 300 study centers across more than 30 countries. Two Phase II single-arm clinical trials in previously-treated and treatment-naïve ALK+ NSCLC patients, are fully enrolled and ongoing. In addition, two Phase III clinical trials comparing ceritinib with chemotherapy in treatment-naïve and in previously-treated patients, are ongoing and actively recruiting patients worldwide.

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