Zioxtenzo: Withdrawal of the marketing authorisation application

Zioxtenzo is a medicine that contains the active substance pegfilgrastim. It was to be available as a solution for injection under the skin.

Zioxtenzo was developed as a 'biosimilar' medicine. This means that it was intended to be highly similar to a biological medicine (the 'reference medicine') already authorised in the European Union. The reference medicine for Zioxtenzo is Neulasta.

Zioxtenzo was to be used in cancer patients to treat neutropenia (low levels of neutrophils, a type of white blood cell that helps fight infection).

Neutropenia is a side effect of certain cytotoxic (cell-killing) cancer treatments and can lead to development of serious infections. Zioxtenzo was to be used to reduce the duration of neutropenia and the occurrence of febrile neutropenia (neutropenia with fever).

The active substance in Zioxtenzo, pegfilgrastim, consists of filgrastim that has been 'pegylated' (attached to a chemical called polyethylene glycol). Filgrastim is very similar to a human protein called granulocyte-colony-stimulating factor (G-CSF). It encourages the bone marrow to produce more neutrophils and improves the patient's ability to fight off infections.

Because filgrastim is pegylated, its removal from the body is slowed down, allowing the medicine to be given less often.

The company presented results of studies designed to show that Zioxtenzo is highly similar to its reference medicine Neulasta in terms of chemical structure, purity, the way it works and how the body handles the medicine. In addition, two studies in patients receiving cancer medicines compared the safety and effectiveness of Zioxtenzo and Neulasta.

The application was withdrawn after the CHMP had evaluated the initial documentation provided by the company and formulated a list of questions.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

Based on the review of the data, at the time of the withdrawal, the CHMP had two main concerns and was of the provisional opinion that Zioxtenzo could not have been approved as a biosimilar of Neulasta.

One concern was that study results were not able to show that the concentrations of pegfilgrastim in blood were the same after taking Zioxtenzo and Neulasta. The other concern was the lack of a certificate of Good Manufacturing Practice (GMP) for the medicine's manufacturing site. An inspection of the site will therefore be needed before the medicine can be approved.

At the time of the withdrawal, the company had not demonstrated that Zioxtenzo is highly similar to Neulasta and an inspection to confirm that it was being manufactured according to GMP standards had not yet taken place.

In its letter notifying the Agency of the withdrawal of the application, the company stated that it would not be able to provide the additional data required by the CHMP within the timeframe allowed for the procedure.

The company informed the CHMP that there is no impact of the withdrawal of Zioxtenzo on ongoing clinical trials and there are no compassionate use programmes for Zioxtenzo.