Monoclonal antibodies and the challenge of substitution

Healthcare payers are eagerly awaiting the arrival of biosimilar competition in the innovative monoclonal antibody sector in order to drive down drug prices and increase patients’ access to these medicines. As the first to introduce scientific and regulatory requirements for the approval of biosimilars in 2004, the European Union (EU) has emerged as a testing ground for biosimilars. In view of the lack of stance of EU governments and national institutions on substitution for biosimilars, hospitals and healthcare structures logically took up this major issue.

Building a consensus, however, on substitution practices among physicians, pharmacists and administrative departments in health facilities appears to be very difficult. The recent experience of the Assistance-Publique Hôpitaux de Paris (AP-HP) – the largest public hospital group in Europe with 22,000 beds and caring for 12 million patients annually – in this field shows that it is, however, possible.

The Committee on Medicinal Products (COMED) of AP-HP is in charge of listing the medicines on the hospital drug formulary or making a decision on whether drugs and therapeutic equivalents should enter into a competition. COMED recently met the challenge of assessing the infliximab biosimilars marketed in the EU from a medical point of view and had to position itself on the interchangeability and substitution issues of biosimilars within the hospitals of the AP-HP. In 2015, COMED of AP-HP decided that infliximab biosimilars and their originator (Remicade, corresponding to a 42-million-Euro expense per year for AP-HP) could be considered as therapeutically equivalent and, thus, could be authorized to participate in the same tender.

In reaching this conclusion, COMED followed a rigorous decision-making process made up of several steps and which included the following:
• assessment of the therapeutic equivalence between the two infliximab biosimilars and the originator (without switches and with switches in ankylosing spondylitis and rheumatoid arthritis)
• evaluation of the risk management plan for the infliximab biosimilars compared to Remicade
• assessment of the immunogenicity data of the biosimilars provided by laboratories (observational studies in ankylosing spondylitis, rheumatoid arthritis and Crohn’s disease without switches and with switches)
• budget impact analysis of listing one or several infliximab products (biosimilars or not) on the hospital drug formulary.

In addition to its decision, COMED made two recommendations. First that a vigorous post-approval surveillance (full traceability) of these products should be implemented in the AP-HP following the tender. Second, that physicians should be encouraged to take part in the registries that will be implemented by the medical disciplines concerned in the AP-HP.

The tender related to infliximab products in the AP-HP was actually only implemented for naïve patients, as the current French law does not allow switching from brand-name biologicals to biosimilars for ‘pretreated’ patients. In 2015, an infliximab biosimilar finally won the tender that resulted in an estimated 45% discount of the price, equivalent to an estimated Euros 6 million gain per year for the AP-HP. On top of that, the re-negotiation of the brand-name infliximab price generated more than Euros 1 million in savings for the institution.

Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.

Abstracted by Dr François Bocquet of the AP-HP and the Faculty of Pharmacy, Paris Descartes University, Sorbonne, Paris, France.

Related articles
Switching between different ESAs

Biosimilars and interchangeability

1. Bocquet F, Paubel P. First monoclonal antibody biosimilars: tackling the challenge of substitution. J Med Econ. 2016;19(6):645-7.


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