Votrient: Withdrawal of the application to change the marketing authorisation

Votrient is a cancer medicine that contains the active substance pazopanib. It has been authorised since June 2010 for treating advanced renal-cell carcinoma (a type of kidney cancer) and certain forms of soft-tissue cancers.

Votrient was also expected to be used as maintenance treatment in women with cancer of the ovaries, fallopian tube or the peritoneum (a membrane that lines the abdomen) whose disease had improved or remained stable after first-line chemotherapy.

It was to be used in women with cancer of stage II to IV according to the International Federation of Gynecology and Obstetrics classification.

Votrient was also expected to be used as maintenance treatment in women with cancer of the ovaries, fallopian tube or the peritoneum (a membrane that lines the abdomen) whose disease had improved or remained stable after first-line chemotherapy.

It was to be used in women with cancer of stage II to IV according to the International Federation of Gynecology and Obstetrics classification.

In ovarian, fallopian tube and peritoneal cancer, Votrient is expected to work in the same way as it does in its existing indications.

The active substance in Votrient, pazopanib, is a protein-kinase inhibitor. This means that it blocks some specific enzymes known as protein kinases. These enzymes can be found in some receptors on the surface of cells that are involved in the growth and spread of cancer cells, such as 'VEGFR', 'PDGFR' and 'KIT'. By blocking these enzymes, Votrient can reduce the growth and spread of cancer.

The applicant presented data from one main study involving 940 women with ovarian, fallopian tube or peritoneal cancer whose disease had not worsened after first-line chemotherapy. Patients in the study received either Votrient or placebo (a dummy treatment) for 2 years. The main measure of effectiveness was how long patients lived without their disease getting worse.

The application was withdrawn after the CHMP had evaluated the initial documentation provided by the company and formulated a list of questions to be answered. The company had not yet responded to the questions at the time of the withdrawal.

At the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Votrient could not be approved for use in women with ovarian, fallopian tube and peritoneal cancer.

The CHMP considered that the women included in the main study were not representative of the women for whom the treatment is intended. The average age of women included in the main study was 56 years whereas the average patient is over 60 years of age at the time of diagnosis. In addition, the CHMP was concerned that the study showed a lack of effectiveness in the subgroup of patients older than 65 years who had more advanced disease. Patients in this subgroup were also more likely to suffer serious side effects and to discontinue treatment. There was also a high rate of treatment discontinuation and interruptions in the overall population due to side effects such as high blood pressure and low levels of white blood cells.

Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Votrient in the treatment of women with ovarian, fallopian tube and peritoneal cancer did not outweigh its risks.

In its letter notifying the Agency of the withdrawal of application, the company stated that it withdrew the application because it did not believe that the additional data requested by CHMP would allow the Committee to conclude on a positive benefit-risk balance in the new indication.

The company informed the CHMP that at the time of the withdrawal there were no patients receiving Votrient for the first-line maintenance treatment of ovarian cancer. There are no consequences for patients in other clinical trials or in compassionate use programmes.

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