Tysabri Every 6 Weeks Found as Effective as Standard 4-week Dosing
Tysabri (natalizumab) given every six weeks was found to be similarly effective as the standard four-week dosing schedule at stopping nervous system damage in people with relapsing-remitting multiple sclerosis (RRMS).
That’s according to the full results of the Phase 3b NOVA clinical trial, which compared Tysabri dosing schedules among nearly 500 RRMS patients with the aim of potentially reducing the risks of side effects tied to the therapy’s use.
“Our findings suggest that most patients who are stable on [Tysabri] 4-week dosing can switch to 6-week dosing without clinically meaningful loss of efficacy,” the researchers wrote.
“These results could provide important information for physicians who are making [Tysabri] treatment decisions,” they added.
Biogen, which markets Tysabri and funded NOVA, announced top-line data from the trial last year.
Full results have now been published in The Lancet Neurology, in a study titled “Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial.”
Tysabri is widely approved to treat RRMS; in the U.S., it also is authorized to treat other relapsing forms of MS, including clinically isolated syndrome and active secondary progressive MS.
The medication works to block inflammatory immune cells from getting into the central nervous system, thus reducing the inflammation that drives MS. Tysabri is administered via intravenous (into-the-vein) infusions, and the approved dosing schedule is 300 mg given every four weeks.
Because it blocks the activity of the immune system in the brain, Tysabri can increase the risk of a rare but serious brain infection called progressive multifocal leukoencephalopathy (PML). Data from a prescribing database called TOUCH, which tracks outcomes for more than 35,000 patients treated with Tysabri, suggested that giving treatment at an extended dosing interval — every six weeks, rather than every four — can substantially reduce the risk of PML.
Biogen launched the NOVA study (NCT03689972) to evaluate the efficacy of the extended interval dosing schedule in patients. In the trial, 499 adults with RRMS who had been on stable Tysabri treatment for at least one year, under the approved every-four-week schedule, were randomly assigned to continue that dosing or to switch to receiving the therapy every six weeks instead.
The trial’s main goal was to compare the effect of the two regimens on disease lesions after 72 weeks, or just under a year and a half.
For the most part, the results were comparable: after 72 weeks, 82% of patients in the every-six-weeks group had no new lesions, as did 78% of those given the therapy every four weeks. One new lesion was reported in 2% of the patients on the six-week regimen, and in 3% of those in the every-four-week group. Less than 1% of participants in either group had two new lesions. For most other patients, data on new lesions were not available.
“The proportions of participants with new or newly enlarging … lesions over 72 weeks of treatment were similar in both groups,” the researchers wrote.
However, there were two outliers, both in the every-six-weeks group. One patient tested positive for antibodies against the John Cunningham virus, which is a risk factor for PML. This patient elected to discontinue Tysabri, and did not switch to another treatment. A few months later, the patient had a relapse, and a subsequent MRI showed 30 new lesions.
The other outlier in the every-six-weeks group gradually developed 25 new lesions over the course of the clinical trial. Per trial protocol, all lesions were assumed to be related to MS, and were counted as such. However, at week 72, the patient tested positive for PML, despite having no obvious symptoms of infection. It is therefore not entirely clear whether these lesions were truly related to MS, or were a result of an insidious infection.
Overall, the average number of new lesions was 0.2 in the every-six-weeks group and 0.05 in patients given the standard dosing schedule. The difference was driven mainly by the two outliers, and it was not statistically significant in the primary analysis.
Other MRI-based measures were generally comparable between the two groups, and nearly all (97–98%) of the participants in both groups were relapse-free throughout the 72-week trial. The average relapse rate was 0.00013 relapses per year in the every-six-week group and 0.00010 relapses per year in the standard dosing group.
The proportion of patients who experienced disability progression lasting at least six months, as well as those with no evidence of disease activity at 72 weeks, also were similar between the groups.
“There were no clinically meaningful differences in secondary clinical or MRI endpoints at week 72 between the once every 6 weeks and once every 4 weeks dosing groups,” the scientists wrote.
“Taken together, the effect of the two participants with extreme lesion numbers, coupled with the secondary and exploratory findings, support the hypothesis that differences in the primary outcome are not clinically meaningful,” they added.
Safety-related outcomes were generally similar in both groups — roughly one in 10 patients in both groups reported any side effects deemed related to treatment, and rates of severe and serious adverse events were comparable. The only case of PML was the asymptomatic case identified in the patient with 25 lesions.
“The safety findings in this study were consistent with the known safety profile of [Tysabri],” the researchers wrote.
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