EMA Recommends Refusal of the Marketing Authorisation for Etirinotecan Pegol

It was intended to be used to treat breast cancer with brain metastases

On 20 July 2017, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product etirinotecan pegol (Onzeald), intended for the treatment of advanced breast cancer which has spread to the brain.

The company that applied for authorisation is Nektar Therapeutics UK Limited. It may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

Onzeald is a cancer medicine that contains the active substance etirinotecan pegol. It was to be available as a powder to be made into a solution for infusion into a vein.

It was expected to be used to treat adults with breast cancer that had spread to the brain who have already received other treatment.

The active substance in Onzeald, etirinotecan pegol, consists of irinotecan (a cancer medicine that belongs to the group topoisomerase inhibitors) that has been pegylated (attached to a polyethylene glycol).

Irinotecan blocks topoisomerase I, an enzyme that is involved in copying cell DNA. By blocking the enzyme, cancer cells are prevented from multiplying and they eventually die.

Irinotecan has been authorised in the EU for a number of years for the treatment of colorectal cancer.

Because it is pegylated in etirinotecan pegol, the medicine is removed from the body at a slower rate, allowing the medicine to be given less often.

What did the company present to support its application? 

The company presented the results of one main study involving 852 patients with breast cancer that had spread to other parts of the body who had been treated with at least 2 other cancer medicines. In this study, etirinotecan pegol was compared with standard cancer medicines chosen by the treating doctor, and the main measure of effectiveness was overall survival.

The CHMP considered that the benefit of etirinotecan pegol in the treatment of breast cancer that had spread to the brain had not been sufficiently demonstrated.

The claim of effectiveness relied on data from a subgroup of patients from a main study which, overall, failed to convincingly show the effectiveness of etirinotecan pegol. The CHMP considered that the data from this subgroup, which were not supported by additional studies, were not sufficient to prove the effectiveness of etirinotecan pegol in patients whose breast cancer had spread to the brain, even when analysed by different methods.

Therefore, the CHMP was of the opinion that the study did not provide enough evidence on the benefits of etirinotecan pegol and recommended that the marketing authorisation be refused.

The company informed the CHMP that there are no consequences for patients in clinical trials with etirinotecan pegol.