Tocilizumab Biosimilars Approaching: Developments on Three Fronts

This IL-6 is approved for treating several autoimmune diseases, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. Roche’s reference product Actemra^® was also the subject of an Emergency Use Approval for the treatment of COVID-19.

In 2021 Roche’s U.S. sales of Actemra totaled $1.9 billion. In a second-quarter conference call, Roche disclosed that sales increased substantially because of the drug’s utilization in patients hospitalized with COVID-19.

The principal patent for the reference agent’s rheumatoid arthritis indication was said to expire as early as 2015, and there appears to be several secondary patents in play. There is little public clarity on this point. As a result, tocilizumab may be another poster child for skinny label approvals, where approval is limited to indications that are off-patent (and certainly not COVID-19 related indications). Of course, the EUA will likely not come into play here, as it is certainly subject to a patent that will expire many years from today. Once the EUA expires, there is no guarantee that the FDA will grant a traditional approval for this indication.

With this level of revenue, and expired patents, one might think there were several competitors vying for a piece of this market. We could identify only three who have included tocilizumab in their active pipelines.

Fresenius Kabi’s MSB11456

Fresenius Kabi announced August 1 that FDA accepted its application for the Actemra biosimilar. A decision is expected during the second quarter of 2023. If the path to approval goes well, Fresenius Kabi will be positioned for a third-quarter 2023 launch of the first tocilizumab biosimilar.

One interesting aspect of this biosimilar is that Roche first introduced Actemra in 2010 as an intravenously administered biologic. The subcutaneous (SC) form was introduced in 2013; yet clinical testing of MSB11456 has been with the SC formulation. Roche is moving patients to the SC drug, which means that Fresenius Kabi is placed well if it obtains approval. The company is seeking biosimilar approval for both the intravenous and SC forms of the reference drug.

Bio-Thera’s BAT1806

Guangzhou, China–based Bio-Thera Solutions partnered with Biogen in 2021 for the manufacture and commercialization of its tocilizumab biosimilar. The company’s phase 3 clinical trial is complete, and the partners announced the positive results in June 2022. In this study the intravenous infusion of BAT1806 was tested against the intravenous infusion of Actemra.

This timing would seem to indicate a pending 351(k) application, likely before the end of this year, with perhaps a late 2023 decision and early 2024 launch.

Celltrion’s CT-P47

Celltrion expects initial results for its phase 1 trial of CT-P47 in October 2022. Not wanting to lose further time, its phase 3 trial for CT-P47 was initiated this month, with an estimated primary completion date of August 2023. This double-blind trial also tests the intravenous formulations of tocilizumab, in approximately 450 patients.

With these dates in mind, an FDA filing could be made by December 2023, with a decision in late 2024.