Zometa: Withdrawal of the application to change the marketing authorisation

Zometa is a medicine that contains the active substance zoledronic acid. It is approved for use as a drip into a vein every three to four weeks to prevent bone complications such as fractures in adults with advanced cancer that is affecting the bone. Zometa can also be used to treat hypercalcaemia (high levels of calcium in the blood) caused by tumours.

Zometa has been authorised since March 2001. It is available in all European Member States.

Zometa was expected to be used as an adjuvant (add-on) in the treatment of early breast cancer in women who have not been through the menopause. Early breast cancer is breast cancer that has not spread and has been treated by surgery. Zometa was only to be used if the breast cancer was 'hormone receptor positive' (the cancer is likely to respond to hormonal treatment), and in combination with hormonal treatment.

The way Zometa is expected to works in early breast cancer is not fully elucidated. Zoledronic acid, the active substance in Zometa, blocks an enzyme called 'farnesyl pyrophosphate synthase'. By blocking this enzyme, it was expected to prevent the growth of cancer cells and cause their death.

The company provided data from one main study to support the use of Zometa in early breast cancer. The study included 1,803 women previously treated with surgery who received Zometa every six months for three years, and were followed up for five years. The study compared anastrozole and tamoxifen (medicines used in hormone-receptor positive breast cancer) with or without Zometa. All women also received goserelin, a medicine that suppresses the activity of the ovaries. The study was 'open label': both the doctor and the patient knew which treatment they were using. The study measured 'disease-free survival' (how long the patients lived without cancer).

The application was withdrawn after 'day 90'. This means that the CHMP had evaluated the documentation provided by the company and formulated a list of questions. The CHMP was assessing the company's responses to the questions at the time of the withdrawal.

Based on the review of the data and the company's responses to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Zometa could not have been approved for the adjuvant treatment of early breast cancer.

The Committee had concerns that the anti-tumour activity of Zometa when used as add-on had not been sufficiently supported by the data from the study. It also had concerns regarding the way the study in early breast cancer had been carried out. The Committee noted that the treatments used in the control groups to which Zometa was compared were not all representative of the standards of care in Europe. The Committee also had concerns regarding the reliability of the data collected during the study.

Therefore, at the time of the withdrawal, the CHMP was of the opinion that the medicine could not have been approved based on the data presented by the company.

The letter from the company notifying the Agency of the withdrawal of the application is available under the tab 'All documents'.

The company informed the CHMP that this withdrawal does not an impact on ongoing clinical trials with Zometa.

If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.

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