Ceritinib (Zykadia) Recommended for Approval in EU

Zosia Chustecka

February 27, 2015

The European Medicines Agency (EMA) has recommended granting a conditional marketing authorization for ceritinib (Zykadia, Novartis Pharmaceuticals Corporation) for the treatment of certain patients with advanced non–small cell lung cancer (NSCLC). In addition, the agency has recommended approval of a novel formulation of the colony-stimulating factor pegfilgrastim (Ristempa, Amgen Inc) and an extension of indications for bevacziumab (Avastin, Roche/Genentech) to include use in the treatment of cervical cancer.

Ceritinib is a novel targeted agent that homes in specifically on anaplastic lymphoma kinase (ALK)–positive NSCLC, which is found in about 2% to 7% of patients with NSCLC.

The indication that has been recommended for ceritinib in the European Union is use in the treatment of ALK-positive NSCLC in patients with advanced disease who have already been treated with crizotinib (Xalkori, Pfizer Inc), the first targeted agent for this patient population.

The EMA noted that not all patients with ALK-positive disease respond to crizotinib, and patients who do respond eventually stop responding and show disease progression. Therefore, "ceritinib provides a treatment option for a high unmet medical need in patients previously treated with crizotinib, as treatment options are currently very limited," it said.

The indication is similar to that given in the approval in the United States, granted by the Food and Drug Administration in April 2014.

The EMA noted that, although the data supplied by the manufacturer show that ceritinib's benefits for treating patients with this condition were clinically relevant and outweighed the risks for adverse effects, the data available so far are based on two uncontrolled studies. Therefore, its Committee for Medicinal Products for Human Use (CHMP) recommended a conditional marketing authorization and requested further results from ongoing studies and a comparative phase 3 study within the next 3 years.

The opinion adopted by the CHMP will now be sent to the European Commission for the adoption of a decision on EU-wide marketing authorization. Once a marketing authorization has been granted, a decision about price and reimbursement will then take place at the level of each EU member state after a consideration of the potential role and use of this medicine in the context of the national health system of that country.

Pegfilgrastim Also Recommended

Also recommended for EU approval is a novel formulation of a colony-stimulating factor, pegfilgrastim (Ristempa, Amgen Inc).

The indication recommended for approval is reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).

The EMA proposes that use of the product be initiated and supervised by physicians experienced in oncology and/or hematology, and noted that a pharmacovigilance plan for Ristempa will be implemented as part of the marketing authorization.

The active ingredient, filgrastim, a recombinant human granulocyte colony-stimulating factor, is already marketed by Amgen as Neupogen, and has enjoyed huge sales ($1.4 billion in 2013). However, this product is now coming off patent, and a number of "biosimilar" products have already appeared in Europe. The first of what looks to be several biosimilars in the United States has just been recommended for approval.

The new product now recommended for EU approval is a pegylated formulation of filgrastim, with a new brand name and new patent protection.

Bevacizumab Use Extended to Cervical Cancer

At its February meeting, the CHMP also recommended an expansion of the indications for bevacizumab (Avastin, Roche/Genentech), which is already marketed for the treatment of several cancer types, including colorectal cancer. The new indication is for its use in the treatment of cervical cancer, a use that is already approved in the United States. That approval was based on a phase 3 trial that showed significantly improved overall survival.

The new EU indication for bevacizumab would cover its use in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy and who have persistent, recurrent, or metastatic carcinoma of the cervix.

There is also a very small change recommendation in the indication already approved for panitumumab (Vectibix, Amgen Inc). This drug was already approved for use in the treatment of adult patients with wild-type RAS metastatic colorectal cancer as a first-line drug in combination with the FOLFOX (5-fluorouracil plus leucovorin with oxaliplatin) chemotherapy regimen; the new indication will specify that it can also be used with the FOLFIRI (5-fluorouracil plus leucovorin with irinotecan) chemotherapy regimen.


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