Tysabri Safe and Effective Taken Every 6 Weeks, NOVA Trial Finds
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Tysabri (natalizumab) given every six weeks was as safe and effective over nearly 1.5 years of use as its approved four-week dosing in people with relapsing-remitting multiple sclerosis (RRMS), according to top-line data from the Phase 3b NOVA study.
Tysabri is typically administered every four weeks, or about once per month. But emerging evidence indicates that less frequent dosing could maintain efficacy while lowering the risk of side effects, including the rare but serious brain infection known as progressive multifocal leukoencephalopathy (PML).
“The NOVA study provides the first prospective, randomized efficacy data of every six-week dosing with [Tysabri], building on its well-established clinical profile and the real-world findings,” Maha Radhakrishnan, MD, chief medical officer at Biogen, which markets the therapy, said in a press release.
Tysabri, approved to treat relapsing forms of MS, works to prevent immune cells from accessing the brain, thereby reducing the altered inflammatory response that damages nerve fibers. However, by suppressing the immune response, Tysabri can increase the risk of opportunistic infections like PML.
The open-label NOVA study (NCT03689972) was initiated by Biogen following an analysis of data from the TOUCH Prescribing Program, which showed that an average dose every six weeks was associated with an 88% reduction in the likelihood of PML compared with the approved, four-week dosing schedule.
The two-year Phase 3b trial enrolled 499 adults with RRMS, who had been treated with 300 mg Tysabri every four weeks for at least one year. Participants were randomly assigned to either continue receiving the therapy into the bloodstream (intravenously) every four weeks, or switch to a six-week regimen.
After 72 weeks (about 1.5 years), the mean number of new brain lesions measured by MRI — a hallmark of MS and the study’s primary goal — was 0.05 for the four-week schedule and 0.20 for those on the six-week dosing interval. This numerical difference, however, was not considered clinically meaningful.
According to the company, this difference was driven by “high number of lesions” in two participants given Tysabri every six weeks. One developed new lesions three months after discontinuing treatment, and the other, with known PML risk factors, developed this infection.
Overall, the proportion of patients who developed new lesions on the six-week regimen was 4.3% and 4.1% among those following four-week dosing.
No statistically significant or clinically meaningful differences in secondary trial goals were seen between the two dosing regimens after 72 weeks.
More specifically, the number of relapses per year among participants taking Tysabri every six weeks was 0.00013, with 97.2% of these patients remaining free of relapses throughout the trial’s duration. In comparison, the annualized relapse rate for the four-week regimen was 0.00010, with 97.9% remaining relapse-free.
The proportion of participants who developed severe T1-hypointense lesions (areas of permanent damage to nerve fibers) was 1.4% with the six-week regimen versus 1.1% for the four-week regimen. Both treatment arms showed 0.5% of patients had gadolinium-enhancing T1 lesions, which reflect regions with active inflammation.
The NOVA findings were consistent with the known safety profile of intravenous Tysabri, and the number of adverse and serious events was similar between both regimens.
Patients who completed the trial’s randomized part and others newly enrolled were invited to enter the study’s extension. In this part, patients are either being treated with Tysabri as a subcutaneous (under-the-skin) injection or as an IV infusion every six weeks for 18 weeks, before switching to the other form of treatment administration for another 18 weeks.
Subcutaneous injection would be an alternative to standard intravenous infusion and one administered in less time, but the FDA rejected this dosing approach in April. Tysabri as an injection treatment is approved in the European Union.
Analysis of study data is ongoing, and details will be shared at a future scientific meeting, the company said. NOVA is expected to finish collecting data in August 2022, and to conclude in February 2023.
“In addition to the safety analyses from the TOUCH Prescribing Program, which showed significant reduction in the probability of PML, the results from NOVA deliver a more comprehensive understanding of the six-week dosing regimen of [Tysabri],” Radhakrishnan added.
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