The European Medicines Agency (EMA) has granted Celltrion marketing authorization for its subcutaneous infliximab biosimilar, Remsima SC, available in the form of a pre-filled syringe or pen. With this approval, Celltrion becomes the first company to develop and market a subcutaneous infliximab biosimilar, a remarkable improvement for ease of administration from the current standard intravenous infusion formulation. In November 2019, Celltrion had received approval of the subcutaneous formulation for rheumatoid arthritis indication. Since then, efforts were underway to extend the indication to all approved for the intravenous version and now the marketing authorization has been extended to ankylosing spondylitis, Crohn disease (CD), ulcerative colitis (UC), psoriatic arthritis, and psoriasis.
Currently there is no regulatory pathway established for improved versions of existing biologics or biosimilars, popularly touted as “bio-betters”, denoting that regulatory extrapolation of clinical data is not possible between an approved and a new improved investigational version of the same biologic or biosimilar. In the EU, Celltrion pursued for an extension of marketing authorization for its intravenous Remsima product, and had to generate substantive clinical data comparing the pharmacokinetics, efficacy and safety of the intravenous and subcutaneous formulations of Remsima for rheumatoid arthritis, ulcerative colitis and Crohn’s disease. Based on the results of a one-year study, 120mg dose of Remsima SC was approved for use in the EU.
In the US market, Celltrion will likely have to go through a 351(a) biologic application for its subcutaneous version since currently there’s no reference subcutaneous product. Currently a phase 3 trial, with 615 participants is underway in USA for Moderate to Severe Active Ulcerative Colitis, this might be used as a basis for regulatory submission to the US FDA. The company had indicated that FDA had exempted it from conducting phase 1 and 2 studies based on the clinical data generated to support the EMA approval. If the biosimilar is approved as a biologic under the 351(a) pathway, it will compete directly against subcutaneous Humira (adalimumab), another anti-TNF mAb with similar indications.
The subcutaneous version is an important progress for the RA and gastroenterology community as the treatment administration becomes easier, quicker and more convenient. It would also offer patients flexibility and control over their treatments. The business proposition for a subcutaneous version is valuable as it will enable a more convenient self-administered option for patients on long-term anti-TNF therapy. However, there is some level of uncertainty if this biosimilar will be interchangeable with other intravenous versions marketed currently.