Biogen Announces Results from Phase 3b NOVA Study Evaluating Every 6-Week Dosing With Natalizumab in Relapsing-Remitting Multiple Sclerosis

Biogen Inc. recently announced results from the 2-year prospective, randomized, interventional, controlled, open-label Phase 3b NOVA study (NCT03689972). NOVA was designed to estimate a potential difference between the efficacy of every 6-week (Q6W) 300mg natalizumab intravenous (IV) administration compared to the efficacy of the approved every 4-week (Q4W) dose in people treated with TYSABRI (natalizumab) (n=499) for relapsing-remitting multiple sclerosis (MS) after at least one year of disease stability on a Q4W IV dosing schedule.

The primary endpoint showed 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), which based on the full trial results is not clinically meaningful. The numerical difference was driven by a high number of lesions occurring in two participants in the Q6W arm – one patient who developed lesions three months after treatment discontinuation and a second patient who developed asymptomatic progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection. The proportion of patients that developed new or newly enlarging T2 lesions in each arm was 4.1%  (Q4W) and 4.3% (Q6W).

There were no statistically significant or clinically meaningful differences in secondary endpoints at week 72 between the Q4W and Q6W treatment arms, and disease activity was well-controlled in both arms:

• Annualized relapse rates were low at 0.00010 (Q4W) and 0.00013 (Q6W), with 97.9% 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).
• Both arms demonstrated 0.5% of participants with gadolinium (Gd) enhancing T1 lesions.

“The NOVA study provides the first prospective, randomized efficacy data of every 6-week dosing with natalizumab, building on its well-established clinical profile and the real-world findings,” 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.”

The NOVA study was initiated to assess the efficacy of Q6W dosing with natalizumab IV administration following analyses from the TOUCH (TYSABRI Outreach: Unified Commitment to Health) Prescribing Program, which showed that extended interval dosing was associated with a significant reduction in the probability of PML. An updated analysis of data from TOUCH showed that an average Q6W dosing regimen is associated with an 88% reduction (hazard ratio 0.118, p<0.0001) in the probability of PML in comparison to the approved Q4W dose.

The safety findings in the NOVA study were consistent with the known safety profile of IV natalizumab and the incidence of adverse events and serious adverse events were similar between the two treatment arms. One patient with asymptomatic PML in the Q6W arm was high-risk based on the known risk factors (anti-JCV antibody index >1.5, and >2 years of TYSABRI treatment), underlying the importance of PML monitoring and risk factor considerations in patients treated with natalizumab.

A complete analysis of the study data is ongoing and detailed results will be shared in a future scientific forum. Natalizumab is available commercially under the brand name TYSABRI and the only approved dose is 300 mg on a Q4W regimen.

TYSABRI is a well-established treatment indicated for relapsing forms of MS in adults that has been proven in clinical trials to slow physical disability progression, reduce the formation of new brain lesions and cut relapses. In the US, TYSABRI is indicated as monotherapy for the treatment of patients with relapsing forms of MS. In the European Union, it is indicated as a single disease modifying treatment (DMT) in adults with highly active relapsing-remitting MS (RRMS) for patients with highly active disease activity despite a full and adequate course of treatment with at least one DMT or patients with rapidly evolving severe RRMS. TYSABRI is approved in over 80 countries, and approximately 220,000 people worldwide have been treated with TYSABRI, with over 880,000 patient-years of experience, based on clinical trials and prescription data.

TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), a rare opportunistic viral infection of the brain which has been associated with death or severe disability. Risk factors that increase the risk of PML are the presence of anti-JCV antibodies, prior immunosuppressant use and longer TYSABRI treatment duration. Patients who have all three risk factors have the highest risk of developing PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk.

TYSABRI also increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses, and serious, life-threatening and sometimes fatal cases have been reported in the post-marketing setting in MS patients receiving TYSABRI. Clinically significant liver injury, including acute liver failure requiring transplant, has also been reported in the post-marketing setting. Other serious adverse events that have occurred in TYSABRI-treated patients include hypersensitivity reactions (eg, anaphylaxis), and infections including opportunistic infections, and a reduction in blood platelet counts.

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, neuropsychiatry, immunology, acute neurology and neuropathic pain. For more information, visit www.biogen.com.