European Medicines Agency Recommends Refusal of the Marketing Authorisation for Masitinib

Masitinib was intended for treatment of gastrointestinal stromal tumours

On 21 November 2013, 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 (Masican), intended for the treatment of malignant gastrointestinal stromal tumour (GIST).

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 this negative opinion.

What is Masican?

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

What was Masican expected to be used for?

Masican was expected to be used to treat gastrointestinal stromal tumour (GIST) in adults whose cancer cannot be removed surgically or has spread and is getting worse despite treatment with imatinib, another medicine used in this cancer.

Masican was designated an orphan medicine, a medicine to be used in rare diseases, on 21 December 2004 for the treatment of malignant GIST.

How is Masican expected to work?

The active substance in Masican, masitinib, is a tyrosine-kinase inhibitor that blocks enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of cancer cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these receptors, Masican 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 applicant presented results of a main study in 44 patients with GIST that could not be removed surgically or that had spread and was resistant to imatinib treatment. The study included a group of patients treated with Masican and one group treated with sunitinib, another medicine of the same class. The study was a phase II study, an exploratory study designed to measure progression-free survival.

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

One of the CHMP’s concerns was that the study was not designed to compare Masican to sunitinib and therefore it was difficult to interpret the results. Although the group of patients treated with Masican appeared to live longer than those treated with sunitinib, the possibility that this was a chance finding could not be ruled out because of the exploratory nature of the study and because other supportive evidence was lacking. Therefore, the Committee concluded that there were insufficient data to establish the benefits of Masican.

The CHMP was also concerned that safety data were only available for a few patients treated with Masican at the proposed dose and this did not allow a proper evaluation of the medicine’s side effects. Finally, there were concerns about the quality control of the medicine during manufacture, which led to uncertainties about the impurities that patients would be exposed to.

Therefore, at that point in time, the CHMP concluded that the benefits of Masican 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 were no consequences for patients currently included in clinical trials or compassionate use programmes with Masican. If patients are in a clinical trial or compassionate use programme and need more information about the treatment, they should contact the doctor who is administered it.