More than 2 years since the approval of the natalizumab biosimilar (reference product, Tysabri), partners Sandoz and Polpharma Biologics have yet to introduce neurologists to the concept of biosimilar prescribing. The reason is a JC virus test submitted by the biosimilar manufacturers, which is required for patients prior to receiving natalizumab treatment, has not yet been approved by the FDA. Natalizumab carries a small risk for progressive multifocal leukoencephalopathy (PML), and the presence of JC virus antibodies can help identify those at higher risk for PML, which is potentially fatal.
The launch of Tyruko was to be a prelude to the main event—the first ocrelizumab (Ocrevus) biosimilar; natalizumab is utilized by around 5% of all patients with relapsing forms of multiple sclerosis (MS) who are receiving pharmaceutical treatment. Tysabri is also approved for use in Crohn’s disease, but utilization is negligible relative to the immunomodulators, anti-TNFs, and interleukin monoclonal antibodies.
In 2024, Ocrevus accounted for about half of all MS drug market share, and approximately $6.1 billion in net US sales revenues in 2024 for its manufacturer (Genentech, and its parent Roche). This represented a 5% increase over the previous year’s sales.
It was first approved March 28, 2017, which would allow its market exclusivity period to run through March 2029. The primary US patent is expected to expire sometime after October 2028.
The following are the leading, publicly disclosed ocrelizumab biosimilar candidates.
Amgen’s ABP 692
Amgen is currently recruiting candidates for a phase 3 trial for its infusible ocrelizumab biosimilar candidate ABP 692. This study, in patients with relapsing-remitting MS, is expected to have preliminary results in January 2027. Amgen has a good record of getting their biosimilars to market first, so we wouldn’t count them out here.
Celltrion’s CT-P53
Similarly, Celltrion has begun recruiting study participants for its infusible product CT-P53, with initial results to be available in early 2027. This investigation plans to test an estimated 512 patients.
Polpharma Biologics’ PB018
Polpharma, which is partnered with Sandoz on the commercialization of its natalizumab biosimilar Tyruko, is also working on the competing MS product ocrelizumab. Designated PB018, this product is in preclinical development. Without a commercialization partner at the moment, Polpharma may be willing to move forward if the FDA does follow through on its intention to no longer mandate large phase 3 comparative efficacy studies. We’ll see whether Sandoz or another major player wants to enter the fray with PB018.
Another Contender, and a Fly in the Ocrevus Biosimilar Ointment
An Iranian company, CinnaGen, has phase 3 results for an ocrelizumab biosimilar product it calls Xacrel. This company does not have a history of marketing to the US, and it is unknown whether it intends to find a marketing partner and file its first 351(k) application in the US.
Interestingly, no record of any BPCIA patent proceeding involving Ocrevus is listed on our favorite patent litigation source, Big Molecule Watch. We’ll need to stay tuned for more developments regarding patent litigation, particularly because there is a significant complicating factor with ocrelizumab.
In 2024, Roche received approval for a subcutaneous injection, known as Ocrevus Zunovo, which offers the convenience of a 10-minute injection versus a 4-hour infusion for the older form, both given every 6 months. If interested in producing a subcutaneous form, a biosimilar maker would have to create its own, assuming this formulation gains increasing utilization. I suspect that the reference manufacturer believes it will be able to convert the majority of its patients and new prescriptions to the subcutaneous form by the time a biosimilar is approved and launched. If that is the case, Roche may be less concerned about vigorously defending its patents on the original intravenous formulation in 2028/2029.
All of the clinical studies by Amgen, Celltrion, or Polpharma mentioned above tested the intravenous formulation only of their biosimilar. Celltrion in particular has some experience in this area, with the 2023 approval of its subcutaneous form of infliximab (dubbed Zymfentra). This approval, subsequent to its initial approval of the biosimilar Inflectra, however, was not considered as a biosimilar but as a follow-on biologic.
