Since some time ago, several oral MS drugs have been available as generics (see also MS-DocBlog Generics in MS therapy), since February 01, 2024, Tyruko® from Sandoz is also the first biosimilar approved and available for MS therapy. The disease-related competence network Multiple Sclerosis (KKNMS) has written a statement on this, which I would like to recommend to my interested readers for reading.
Tyruko® is a Natalizumab biosimilar. Natalizumab, in turn, is a monoclonal therapeutic antibody that was first approved in 2006 under the trade name Tysabi® by Biogen. Tyruko® is thus the replica of a long-known, frequently used and highly effective MS drug. Many of you know it or even use it yourself or have used it. The production of such, usually significantly cheaper replicas is allowed for companies when the patent protection of the original preparation (in this case Tysabri®) has expired.
Biosimilars: similar, but not identical
Now, Natalizumab is a complex biological substance – and mimicking such complex biologics is relatively complicated. Therefore, the term used for replicas of complex biological substances (=biologics) is so-called “biosimilars”. The name thus already expresses it: The replica resembles (English: similar) the original, but is not completely identical to it.
This is because complex biological substances like Natalizumab are produced in living organisms. Such production processes can always lead to certain “biological” differences – this is also referred to as microheterogeneity.
Clear boundaries for variability
However, the variability of a biosimilar must be within a rather narrow corridor – there are clearly defined limits. Simply put, a biosimilar is not identical to the original preparation, but very similar. This strong similarity must also be ensured by a large number of chemical analyses of structure and quality.
Evidence of efficacy and safety
In addition, the effectiveness and safety of the preparation must be demonstrated in the course of the approval of a biosimilar. However, not to the same great extent as was the case with the corresponding original preparation. Therefore, biosimilars can also be sold more cost-effectively, which is ultimately good for our health system. The Natalizumab biosimilar Tyruko® also had to undergo a randomized phase III study (“Antelope”), which was published last year (Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial).
The Antelope Study
This comparative study between Tyruko® and the original preparation (Tysabri®) included 264 adult patients with relapsing MS. In the examination in week 24, the number of new active lesions was similar between the treatment groups. No significant differences were found between the treatment groups in terms of efficacy, safety, tolerability or immunogenicity. Accordingly, one can reasonably rely on the fact that there is no disadvantage, regardless of whether one is treated with the original or the replica preparation.
Validated tests prerequisite for use of the biosimilar
But especially with Natalizumab it is important that the manufacturer of the biosimilar provides appropriately validated tests for regular determination of the JCV antibody status. This is a prerequisite for safe use due to the PML risk of Natalizumab. Such a test has been developed by Sandoz, but was not yet available at the time this text was written. However, all users agree that this is a basic requirement for the use of the Natalizumab biosimilar. If this is ensured, there is nothing against the use of the biosimilar and patients do not have to worry about being inadequately treated.
