Novartis gains US FDA approval for Zykadia

Basel

US Food and Drug Administration (US FDA) has approved Novartis’ Zykadia (ceritinib, previously known as LDK378) for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib[1]. The approval of Zykadia addresses an unmet medical need for patients with this type of lung cancer who have progressed on prior therapy.

“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, 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.”

Lung cancer is the leading cause of cancer death worldwide. The most common type of lung cancer is NSCLC, accounting for 85-90 per cent of all cases[3]. Of those, two to seven per cent are driven by a rearrangement of the ALK gene, which increases the growth of cancer cells and can be identified by a molecular test of the cancer tumour[2]. Despite significant treatment advances for patients with ALK+ NSCLC, disease progression is often inevitable and more options are needed. 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 per cent), liver (42 per cent) and bone (42 per cent)[1].

Among previously-treated patients, Zykadia achieved an overall response rate (ORR) of 54.6 per cent [95 per cent CI, 47-62 per cent] and a median duration of response (DOR) of 7.4 months [95 per cent CI, 5.4-10.1 months][1]. The most common adverse reactions (incidence of at least 25 per cent) were diarrhoea, nausea, elevated transaminases, vomiting, abdominal pain, fatigue, decreased appetite and constipation[1].

“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, 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.”

Zykadia is an oral, selective inhibitor of ALK, an important therapeutic target in lung cancer. ALK is a gene that can fuse with other genes to form an aberrant ‘fusion protein’ that promotes the development and growth of cancer cells[4],[5]. 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.

References:
[1] Zykadia(TM) (ceritinib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; April 2014.
[2] National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung Cancer. NCCN 2014 3:1-148.
[3] American Cancer Society. Lung Cancer – Non-Small Cell Detailed Guide. Available at: http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer. Accessed on March 31, 2014.
[4] Lin E, Li L, Guan Y, et al. Exon Array Profiling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung Cancers. Mol Cancer Res. 2009;7(9):1466-1476.
[5] Shaw A, et al. Targeting Anaplastic Lymphoma Kinase in Lung Cancer. Clin Cancer Res 2011;17:2081-2086.

EP News Bureau – Mumbai