Natalizumab Equally Safe, Effective on 6-Week Dosing Schedule Vs 4-Week Schedule in Multiple Sclerosis
There were no clinically meaningful differences in outcomes for patients with relapsing-remitting multiple sclerosis on an every 6-week dosing schedule (Q6W) for intravenous (IV) natalizumab compared to an every 4-week schedule (Q4W), according to the 2-year prospective, randomized, interventional, controlled, open-label Phase 3b NOVA study. Although there was a numerical difference between the mean number of new or newly enlarging T2 hyperintense lesions at week 72 of 0.05 (Q4W) and 0.20 (Q6W) (p=0.0755), this difference was not clinically meaningful in the context of the full data, and is largely due to 2 individuals with a high number of lesions in the Q6W arm, according to the investigators.
The first of these 2 outliers developed lesions 3 months after treatment discontinuation, whereas the second developed asymptomatic progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection. The percentage of patients who developed new or newly enlarging T2 lesions in each arm was 4.1% (Q4W) and 4.3% (Q6W).
“The NOVA study provides the first prospective, randomized efficacy data of every six-week dosing with natalizumab, building on its well-established clinical profile and the real-world findings 1,2,3,” said Maha Radhakrishnan, MD, chief medical officer at Biogen. “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 natalizumab.”
Across both cohorts, annualized relapse rates were low at 0.00010 (Q4W) and 0.00013 (Q6W), with 97.9% of patients in the Q4W arm remaining relapse-free compared to 97.2% of patients in the Q6W arm. The proportion of patients that developed T1 hypointense lesions in each arm was 1.1% (Q4W) and 1.4% (Q6W), and both arms demonstrated 0.5% of participants with gadolinium enhancing T1 lesions.
According to the investigators, the NOVA study was initiated in response to analyses from the TOUCH Prescribing Program, which showed that extended interval dosing was associated with a significant reduction in the probability of PML. Updated data analysis from TOUCH demonstrated that an average Q6W dosing regimen is associated with an 88% reduction in the probability of PML compared to the approved Q4W dose.
Biogen announces results from Phase 3b NOVA study evaluating every six-week dosing with natalizumab in relapsing-remitting multiple sclerosis [news release]. Biogen; August 2, 2021. Accessed August 4, 2021. http://media.biogen.com/news-releases/news-release-details/biogen-announces-results-phase-3b-nova-study-evaluating-every