European Medicines Agency Recommends Refusal of the Marketing Authorisation for Masitinib

Intended for the treatment of advanced inoperable pancreatic cancer

On 23 January 2014, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product masitinib (Masiviera), intended for the treatment of advanced inoperable pancreatic cancer.

The company that applied for authorisation is AB Science. It may request a re-examination of the opinion within 15 days of receipt of notification of the negative opinion.

What is masitinib?

Masiviera is an anticancer medicine that contains the active substance masitinib. It was to be available as tablets.

What was masitinib expected to be used for?

Masiviera was expected to be used to treat adults with cancer of the pancreas that is locally advanced or metastatic, non-resectable and is accompanied by at least moderate pain or has certain genetic changes that are associated with more aggressive disease. It was to be used in combination with another cancer medicine, gemcitabine.

Masitinib was designated an ‘orphan medicine’ (a medicine to be used in rare diseases) on 28 October 2009 for the treatment of pancreatic cancer.

The active substance in Masiviera, masitinib, is also being assessed for the treatment of another type of cancer, gastrointestinal stromal tumour (GIST).

How is masitinib expected to work?

The active substance in Masiviera, masitinib, is a tyrosine-kinase inhibitor. This means that it blocks certain enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of cells, including the receptors that are involved in stimulating cancer cells to divide uncontrollably. By blocking these receptors, Masiviera might help in controlling cell division and thereby slow down the growth of the cancer.

What did the company present to support its application?

The effects of Masiviera were first tested in experimental models before being studied in humans.

The company presented results of one main study involving 353 patients with advanced or metastatic pancreatic cancer. Masiviera was compared with placebo as an addition to treatment with gemcitabine. The main measure of effectiveness was how long the patients survived with their disease. The company also presented various supporting analyses and information from a supportive study.

What were the CHMP’s main concerns that led to the refusal?

The results of the main study with Masiviera did not show effectiveness in the overall group of patients with advanced or metastatic pancreatic cancer. Although the company presented analyses suggesting that there was a benefit in a subgroup of patients with certain genetic changes associated with more aggressive disease, and in a subgroup of patients with pain, the study was not designed to show benefit in these smaller groups, and the Committee considered that further study would be needed to demonstrate such a benefit.

In addition, Masiviera was associated with significant toxicity. Furthermore, the CHMP had concerns about the quality of the product, in particular about the impurities to which patients might be exposed and about whether commercial batches of the medicine would have the same quality as those used for the studies.

Therefore, at that point in time, the CHMP was of the opinion that the benefits of Masiviera did not outweigh its risks and recommended that the medicine be refused marketing authorisation.

What consequences does this refusal have for patients in clinical trials or compassionate use programmes?

The company informed the CHMP that there are no consequences for patients in clinical trials or compassionate use programmes, who should contact the doctor who is giving masitinib if they require further information.