EU Thumbs Up to Nab-Paclitaxel, Thumbs Down to Masitinib

Zosia Chustecka


November 22, 2013

Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane, Celgene) has been recommended for approval in the European Union for a new indication — use in combination with gemcitabine in the treatment of metastatic pancreatic cancer.

This indication was approved in the United States in September. At the time, the US Food and Drug Administration (FDA) noted that nab-paclitaxel is the first new treatment approved for metastatic pancreatic cancer in nearly 8 years.

The product is already marketed for use in metastatic breast cancer and non-small cell lung cancer.

Negative Opinion on Masitinib

However, the Committee for Medicinal Products for Human Use (CHMP), which considers drugs for approval in the European Union, issued a negative opinion for masitinib (Masican, AB Science) for use in the treatment of gastrointestinal stromal tumor (GIST). This means that the product is not recommended for approval in the European Union. It does not appear to be marketed for human use anywhere, although it has been available for dogs as a treatment for mast cell tumors (as Masivet) since 2009 in Europe.

Masitinib is a tyrosine kinase inhibitor, and so falls into the same class as imatinib (Gleevec, Novartis) and a number of similar agents. One of these is sunitinib (Sutent), which was granted conditional approval in the European Union for use in GIST in 2006.

In the clinical data that were submitted for approval, there was a phase 2 study in 44 patients, of whom some were treated with masitinib and others with sunitinib. However, the CHMP said in a statement that it had concerns about this study as it was not designed to compare the 2 drugs with one another, and "therefore it was difficult to interpret the results."

In addition, the CHMP was also concerned about the paucity of safety data, which did "not allow a proper evaluation of the medicine's side effect." Finally, there were concerns about the quality control of the medicine during manufacture.

Ponatinib Remains on European Union Market

In other opinions, the CHMP noted that the leukemia drug ponatinib (Iclusig, Ariad) remains on the market in the European Union, but new measures are being taken to help reduce the risk for conditions associated with blood clots (such as heart attacks, stroke, and deep vein thrombosis).

Ponatinib was removed from the market in the United States on October 31, after reports of life-threatening blood clots and severe narrowing of blood vessels. In some patients, fatal and serious adverse events occurred as early as 2 weeks after starting ponatinib therapy, and the FDA said that it could not identify a dose level or exposure duration that is safe.

In Europe, on November 8, after reviewing updated information on ponatinib, which is used to treat chronic myeloid leukemia, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency decided to keep ponatinib on the market, but with a strong warning about potential cardiovascular adverse effects.

The CHMP said that its recommendations are broadly in line with those of the PRAC, and that an opinion will now be sent to the European Commission for the product labeling to be updated.

Changes Recommended for Cetuximab

The CHMP recommended changes to be made in the labelling of cetuximab (Erbitux, Merck KGaA) concerning its use in metastatic colorectal cancer. The changes clarify the particular genetic makeup of the cancer that must be present before the drug can be used; specifically, the recommendation is that KRAS is changed to RAS.

Cetuximab is indicated for use in the treatment of patients with epidermal growth-factor receptor (EGFR)-expressing KRAS wild-type metastatic colorectal cancer, but the KRAS is to be changed to RAS.

A similar change of RAS replacing KRAS was also recommended in the contraindications section of the labelling, which states that cetuximab must not be used in patients whose tumors carry mutations in the KRAS gene (change to RAS gene).

The drug is also approved for use in the treatment of head and neck cancer; that labelling remains the same.


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