Withdrawal of the EU Marketing Authorisation Applications for Cavoley and Efgratin

Both contain the active substance pegfilgrastim and were developed as a biosimilar medicine

On 20 December 2018, STADA Arzneimittel AG officially notified the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Cavoley, for reducing neutropenia. On same day, Gedeon Richter Plc officially notified the CHMP that it wishes to withdraw its application for a marketing authorisation for Efgratin, for reducing neutropenia.

Cavoley and Efgratin are medicines that contain the active substance pegfilgrastim, which stimulates the production of neutrophils. They were to be given by injection under the skin. Both were developed as a biosimilar medicine. This means that Cavoley and Efgratin were intended to be highly similar to another biological medicine (the reference medicine) that is already authorised in the EU. The reference medicine for both is Neulasta. More information on biosimilar medicines, you can find here.

Cavoley and Efgratin were to be used in cancer patients to reduce neutropenia. Neutropenia is a side effect of certain cytotoxic cancer treatments. Cavoley and Efgratin were to be used to reduce the duration of neutropenia and the occurrence of febrile neutropenia.

The active substance in Cavoley and Efgratin, 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.

Each company presented results of two studies in healthy people designed to show that Cavoley and Efgratin are highly similar to their reference medicine Neulasta in terms of chemical structure, purity, the way they work and how the body handles the medicine. A further study in patients receiving cancer medicines compared the effectiveness of Cavoley, as well as of Efgratin, and Neulasta. The safety of Cavoley and Efgratin were compared with that of Neulasta across different studies involving healthy people as well as patients with cancer.

The applications were withdrawn after the CHMP had evaluated the initial documentation provided by the companies and formulated a list of questions. The companies 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 some concerns and was of the provisional opinion that both, Cavoley and Efgratin could not have been approved for reducing neutropenia. The CHMP was concerned about the validity of results from studies on how the body handles Cavoley and Efgratin compared with Neulasta. Moreover, information was not available on the possible formation in the body of antibodies against the active substance in Cavoley and Efgratin. Therefore, at the time of the withdrawal, the CHMP was of the opinion that the companies had not demonstrated that Cavoley and Efgratin were highly similar to Neulasta.

In their letters notifying the Agency of the withdrawal of the application, the companies stated that they could not address the CHMP’s concerns within the time allowed.

The companies informed the CHMP that there are no ongoing clinical trials or compassionate-use programmes for Cavoley and Efgratin.