Alpheon had been designed to become a biosimilar medicine of the reference product Roferon-A from F Hoffmann-La Roche and was developed by BioPartners GmbH, based in Baar, Switzerland (acquired by Bioton SA, Poland, in March 2007). Alpheon was manufactured under contract by Rentschler Biotechnologie GmbH & Co KG by expression in recombinant Escherichia coli-bacteria.

BioPartners filed many quality and clinical comparability studies to the EMEA-CHMP. These included comparability studies to Roferon-A on the structure of its active pharmaceutical ingredient, the composition and purity of the medicine, the way it works, the safety and its effectiveness against hepatitis C in 455 patients, measuring how many patients responded to Alpheon after 12 out of the 48 weeks of treatment and six months after stopping treatment.

However, the CHMP had major concerns regarding the comparability of Alpheon and Roferon-A because of differences identified between the two medicines, such as impurities. They also had concerns that there was not enough data on the stability of the active pharmaceutical ingredient and of the medicine that was going to be marketed. Also, the process used for making the finished medicine had not been adequately validated.

The number of patients with hepatitis C responding to treatment with Alpheon and Roferon-A was similar in the clinical study. However, some differences were seen between the two medicines: more patients experienced a return of the disease after treatment with Alpheon was stopped than with the reference medicine, and there were more side effects with Alpheon. In addition, the test used in the study to investigate the potential for the medicine to trigger an immunological response had not been sufficiently validated.

At this point in time, the CHMP was of the opinion that Alpheon could not be considered as a biosimilar medicine of Roferon-A. Hence, it recommended that Alpheon be refused marketing authorisation. Currently, there are no ongoing clinical trials or compassionate use programmes with the product in the EU, but BioPartners still plans to re-file Alpheon.