With a Biosimilar on the Horizon, New Data Give an Important Look at Natalizumab in MS

While biosimilar stakeholders are familiar with biosimilars that treat inflammatory diseases and are becoming increasingly familiar with those that treat cancer, biologics that treat neurological diseases are newly targeted by biosimilar developers. Just last week, Sandoz indicated that it will commercialize a biosimilar of the multiple sclerosis (MS) drug natalizumab (Tysabri).

This week, during the 35th meeting of the European Committee for Treatment and Research in Multiple Sclerosis, held September 11-13 in Stockholm, Sweden, researchers will present data that help contextualize natalizumab’s place in the treatment paradigm for MS.

First, in a poster session, researchers from centers in Sweden will report on clinical outcomes of patients who have been treated with natalizumab for at least 8 years.¹

The researchers derived their data from the Swedish Neuro Registry, which contains data for patients with MS in all university hospitals in the nation. When natalizumab was launched in Sweden in 2006, the registry initiated a study of the drug to monitor long-term safety and effectiveness in the real-world setting.

From 2006 to 2019, 3141 patients with MS were enrolled, and 288 had been treated for at least 96 months. Relapses before treatment were reduced from 388 per 1000 patient-years (PY) to 54 per 100 PY during treatment. In total, 62% of the patients were relapse-free, and 17% had 1 relapse, during the entire treatment period (12% of the patients had missing data). Additionally, all clinical effectiveness measures showed statistically significant improvement from baseline to month 96.

There were 104 serious adverse events reported, including 9 cases of progressive multifocal leukoencephalopathy (PML), 2 of which led to death. The authors note that the advent of testing for human polyomavirus 2, which can cause PML, has likely led to a drop in the incidence of PML.

Overall, write the authors, natalizumab is well tolerated and has sustained effectiveness.

Additionally, another team of researchers, this time from centers in multiple European nations, reported that patients who used extended interval dosing of natalizumab based on trough concentrations, in an effort to lower the risk of PML, were able to maintain their response to the drug.²

In a prospective, multicenter, single-arm trial with a 1-year follow-up and an extension phase of 1 year, 61 patients with MS received natalizumab at extended intervals of more than 4 weeks.

In total, 84% of the patients were able to extend their dosing interval to 5 to 7 weeks, and no patients in the trial developed gadolinium enhancing lesions while undertaking extended doses, and no new or enlarged T2 lesions or relapses have been reported in the extension.

According to the authors, natalizumab maintains efficacy in patients who have personalized dosing based on their individual drug concentrations.

References

1. Kågström S, Fält A, Forsberg L, et al. Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1). Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract P604.

2. van Kempen Z, Hoogervorst E, Kalkers N, et al. Personalized extended interval dosing of natalizumab in multiple sclerosis: a prospective multicenter trial. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract P1340.