EFPIA and EBE welcome the results of the NOR-SWITCH study on biosimilar switching* and acknowledge its preliminary results as a step in the right direction of robust data generation that continues to enhance physician and patient confidence in using biosimilars.

EFPIA and EBE also welcome the effort of the Norwegian authorities and investigators to initiate and carry out the NOR-SWITCH study.

The study aimed to assess disease worsening through a single switch from biologic Remicade® (originator infliximab) to CTP13 (biosimilar infliximab) in disease-stable patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, Crohn’s disease and chronic plaque psoriasis. The protocol indicates the study is being ‘driven by financial motivation’ and switching patients on stable treatment will result in substantial cost savings to the Norwegian government. The preliminary results presented this week indicated that CTP13 is not inferior to the originator in terms of disease worsening in stable patients who have been on Remicade treatment for at least six months.

The study’s conclusion is an important development that will aid physician’s in making evidence based treatment decisions for patients using infliximab. Importantly, while NOR-SWITCH provides evidence for a one way switch from Remicade to CTP13, the study does not and cannot address the following:

• Multiple switches – switching back and forth between Remicade and a specific biosimilar, CTP13,
• Switching between different biosimilar infliximab products, either biosimilar or originator (either in a single switch or a multiple switch)

Although the results offer a valuable source of information for physicians it is important to recognise these results are only relevant to these infliximab products. Biologics are highly complex molecules, treating patients with highly complex diseases and – and that switching stable patients is still nascent in its practice. Conclusions, therefore, from one switching study are not transferrable to all biologic molecules. Assurance needs to be provided that it is safe to switch between medicines to account for the differences between molecules, diseases and – most importantly – patients.

EFPIA and EBE note furthermore that the primary endpoint for the study is ‘disease worsening’ in the six indications studied. In the study, the different disease worsening endpoints have, however, been pooled together to calculate the overall ‘proportion of patients experiencing disease worsening’. As disease worsening is defined differently across different indications – accounting for different sensitivities, patient factors (e.g. co-morbidities) and dosing, etc. – the pooling of disease worsening endpoints means the study was not statistically powered to make conclusions on each disease individually, consequently it is a generalised result that may not be a true measure of non-inferiority for each individual indication.

EFPIA and EBE also want to re-iterate the importance of physician involvement and patient awareness as well as monitoring in switching decisions as they are made for biologics. We therefore encourage more switching studies with other biologic medicines in other therapeutic areas so that evidence can accrue to build physician and patient confidence in all biologic medicines, including biosimilars.

EFPIA and EBE call on all stakeholders to acknowledge that building evidence is important in building trust for other biologics therapeutic areas over the medium and long-term. EFPIA, EBE and their members are committed to engaging with stakeholders to help promote dialogue and the creation of a sound evidence base to ensure the safety of patients and safeguard the efficacy of their treatments.

Conclusions:

EFPIA and EBE reinforce the central role of the physician with the patient in making the decision on the appropriate treatment for both naïve and disease-stable patients:

• the prescribing physician must always retain the option to designate which biological product should be dispensed. Treatment decisions must be made first on the basis of clinical judgment and then on the overall value proposition offered by individual medicines; and
•  the treating physician, in consultation with the patient, should make any  decision to switch patients from one biological product to another. Where switching occurs, it must be accompanied by adequate clinical monitoring and the patient must be informed appropriately at all times.

* https://clinicaltrials.gov/ct2/show/NCT02148640