European Medicines Agency Recommends to Refuse a Change to the Marketing Authorisation for Bevacizumab

The change concerned an extension of indication to add treatment of newly diagnosed glioblastoma

On 22 May 2014, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of a change to the marketing authorisation for the medicinal product bevacizumab (Avastin). The change concerned an extension of indication to add treatment of glioblastoma.

The company that applied for the change to the authorisation is Roche Registration Ltd. It may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

Avastin is a cancer medicine that contains the active substance bevacizumab. It is available as a concentrate that is made up into a solution for infusion.

Avastin has been authorised in the EU since 12 January 2005. It is used, in combination with other chemotherapy medicines, to treat certain types of the following cancers: cancer of the colon or rectum; breast cancer; lung cancer; kidney cancer; cancer of the ovary; cancer of the fallopian tube or the peritoneum.

What was bevacizumab expected to be used for?

Bevacizumab was also expected to be used to treat adult patients with newly diagnosed glioblastoma in combination with radiotherapy and temizolomide.

In glioblastoma, bevacizumab is expected to work in the same way as it does in its existing indications. The active substance in Avastin, bevacizumab, is a monoclonal antibody, that has been designed to recognise and attach to vascular endothelial growth factor (VEGF).

What did the company present to support its application?

The company presented the results from one main study with bevacizumab involving 921 patients with newly diagnosed glioblastoma. In the study, patients received bevacizumab or placebo in addition to treatment with radiotherapy and temozolomide.

The main measures of effectiveness were overall survival and progression-free survival.

What were the CHMP’s main concerns that led to the refusal of the change to the marketing authorisation?

The CHMP noted that the effectiveness of bevacizumab in combination with radiotherapy and temozolomide had not been sufficiently demonstrated. Although there was an improvement in progression-free survival, it could not be considered clinically relevant because of limitations in the methods available to measure the size of brain tumours. In addition, there was no benefit in terms of overall survival.

Therefore, at that point in time, the CHMP was of the opinion that the benefits of bevacizumab in the treatment of glioblastoma did not outweigh its risks. Hence, the CHMP recommended that the change to the marketing authorisation be refused.

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 with glioblastoma receiving bevacizumab in clinical trials: patients will continue to receive bevacizumab in the ongoing and future clinical trials.

What is happening with bevacizumab for treatment of other cancers?

There are no consequences on the use of bevacizumab in its authorised indications.