Biosimilar Comparable in Safety, Efficacy to Tysabri in Phase 3 Trial

PB006, a biosimilar to Biogen’s approved treatment Tysabri (natalizumab), showed similar safety and efficacy as the original medication in people with relapsing-remitting MS (RRMS), according to data from a Phase 3 clinical trial.

“The Antelope trial reported equivalence between [PB006 and Tysabri] treatment across efficacy, safety, and secondary MRI and clinical outcomes,” researchers wrote.

The findings may support the approval of PB006, the first biosimilar antibody developed for multiple sclerosis (MS), as an alternative to Tysabri.

The study detailing the results, “Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis,” was published in JAMA Neurology.

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Over a dozen treatments are approved in the U.S. for relapsing types of MS. Many of these medications are biologics, meaning the active agent requires the use of living cells to produce. Antibody-based medicines are a common form of biologic.

Biosimilars are biologics that are designed to have equivalent activity to approved biologic medicines. They can introduce more competition into healthcare marketplaces, helping to drive down costs of treatment.

Functionally, biosimilars are comparable to generic versions of traditional medicines, but whereas traditional generics can be synthesized to be chemically identical to the name-brand product, there are special manufacturing and regulatory considerations for biologics.

Tysabri is an antibody-based biologic therapy that works to prevent inflammatory immune cells from getting into the brain and spinal cord. The name-brand medication has been approved to treat relapsing MS in the U.S. since 2004.

The Antelope trial reported equivalence between [PB006 and Tysabri] treatment across efficacy, safety, and secondary MRI and clinical outcomes.

PB006 is a proposed biosimilar to Tysabri that is being developed by Polpharma Biologics. The company sponsored a Phase 3 clinical trial called ANTELOPE (NCT04115488) to compare the efficacy and safety of PB006 with Tysabri.

The study enrolled 264 adults with RRMS, average age 36.7 years, at sites in Belarus, Croatia, Georgia, Moldova, Poland, Serbia, and Ukraine. Participants were randomly assigned to take PB006 or Tysabri, both given via infusion into the bloodstream every four weeks at a dose of 300 mg for about half a year (24 weeks).

Then, those on Tysabri were re-randomized to continue on Tysabri or switch to PB006, with treatment continuing to about one year (48 weeks) across all groups.

“PB006 is the first biosimilar monoclonal antibody therapy developed for multiple sclerosis (MS) treatment. … The primary objective of the Antelope study was to confirm equivalent efficacy between [PB006 and Tysabri] in patients with RRMS,” the researchers wrote.

Study compared effect of treatment on number of new active lesions on MRI

The study’s main goal was to compare the effect of treatment on the number of new active lesions visible — both new lesions with active inflammation and new or enlarging lesions — on MRI scans.

Results showed that, after 24 weeks, the average difference in the number of new active lesions between the PB006 and Tysabri groups was 0.17 lesions, a non-significant difference.

“[PB006] demonstrated similarity to [Tysabri] in the primary efficacy end point of cumulative number of new active lesions over 24 weeks,” the researchers wrote.

The number of lesions was also comparable between groups at the end of the 48-week study. Rates of relapses and disability progression similarly showed no significant differences between the PB006 and Tysabri groups throughout the study.

Safety data were comparable between Tysabri and the proposed biosimilar, with similar rates of side effects in both treatment groups and no unexpected findings given the established safety profile of Tysabri. Importantly, there were no unanticipated safety issues for patients who switched from Tysabri to PB006.

Results related to immunogenicity — the immune system launching a response against the medication — also were comparable between PB006 and Tysabri.

“The clinical efficacy, safety, and immunogenicity of the proposed biosimilar natalizumab matched the reference natalizumab in the tested setting, with no clinically relevant differences observed,” the scientists concluded. “The results from this phase 3 trial support biosimilarity of proposed biosimilar natalizumab PB006 to its reference medicine in RRMS.”