In an interview with PharmaShots, Monica Mann, Vice President, Medical Affairs for Global MS and Pipeline at Biogen shared her views on the data of Tysabri, Vumerity & highlights of new digital health research to predict multiple sclerosis disease progression

Shots:

• Monica spoke about detailed results of the new real-world & clinical data on the long-term use of Tysabri & real-world analyses showing high rates of persistence and adherence for Vumerity
• RW analysis of Tysabri showing results from two studies US TOUCH and Ph3B (NOVA) whereas, RW analysis of Vumerity talks about retrospective study and claims data
• This interview also talks about the Biogen’s continued efforts to bring innovation in MS with digital health research using MRI Scans, SELs to track disease progression

Smriti: Would you please explain the details (MOA, ROA, formulations, etc.) of TYSABRI & VUMERITY?

Monica Mann: TYSABRI has been shown to bind to α4-integrin on certain lymphocytes, inhibiting their migration into the central nervous system (CNS), which may prevent subsequent damage to neurons. TYSABRI is administered through an intravenous (IV) infusion and the approved dose is 300mg on an every four week dosing regimen.

VUMERITY’s active metabolite (MMF) has been shown to activate the Nrf2 pathway and its active ingredient is diroximel fumarate. Nrf2 is an intrinsic cellular defense system that defends against oxidative and inflammatory stress, and its activation maintains BBB integrity and protects against neuronal cell death. VUMERITY is presented as gastro-resistant hard capsules and the starting dose for VUMERITY is 231 mg twice a day orally. After seven days, the dose should be increased to the maintenance dose of 462 mg (administered as two 231 mg capsules) twice a day orally.

NOVA Phase 3b study show that every six-week (Q6W) dosing with 300 mg natalizumab IV provides a high level of efficacy in controlling multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS who switched to Q6W after at least one year of disease stability on the approved every four-week (Q4W) IV dosing schedule. 

Smriti: Can we discuss the study design of the Ph3b (NOVA) clinical trial?

Monica Mann: NOVA (NCT03689972) was a randomized, controlled, prospective, open-label, multinational trial including participants diagnosed with MS aged 18-60 years who had been treated with the approved dose of natalizumab IV, 300 mg every four weeks, with no relapses for at least 12 months. Study participants (n=499) were randomly assigned across 89 study sites in 11 countries to either receive every six-week dosing (n=251) or continue treatment with every four-week dosing (n=248).

The NOVA study was designed to assess the efficacy and safety 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 of approximately every six weeks was associated with a significant reduction in the probability of progressive multifocal leukoencephalopathy (PML). NOVA was not designed to assess the risk of PML.

Smriti: Take us through the key findings of the Ph3b (NOVA) clinical trial in detail?

Monica Mann: Data from the NOVA Phase 3b study show that every six-week (Q6W) dosing with 300 mg natalizumab IV provides a high level of efficacy in controlling multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS who switched to Q6W after at least one year of disease stability on the approved every four-week (Q4W) IV dosing schedule. The primary endpoint was the mean number of new or newly enlarging T2 hyperintense lesions, and key secondary and exploratory endpoints included annualized relapse rate (ARR), confirmed disability progression, gadolinium (Gd) enhancing T1 lesions, T1 hypointense lesions and NEDA.

The safety findings in the NOVA study were consistent with the known safety profile of IV natalizumab, and the incidence of SAEs and AEs was similar between the two treatment arms.

Smriti: How has TYSABRI proven to be clinically beneficial when administered every 6 weeks rather than every 4 weeks for the treatment of MS?

Monica Mann: The NOVA study builds on real-world studies which suggest that an extended dosing interval with natalizumab IV offers similar efficacy to the approved dosing regimen, as well as separate safety analyses from the TOUCH Prescribing Program that showed an average Q6W dosing regimen is associated with a significant reduction in the probability of PML, a rare but serious brain infection.

Smriti: How has the comparative study of VUMERITY vs TECFIDERA proved VUMERITY to be the better option for the treatment of MS?

Monica Mann: With VUMERITY, we have seen both in a randomized study and real-world settings the benefits of improved gastrointestinal tolerability when it comes to continually managing MS, which can contribute to higher rates of persistence and adherence to DMT and improved longer-term outcomes.

EVOLVE-MS-2 was a randomized, double-blind, five-week, multi-center Phase 3 study to evaluate the gastrointestinal (GI) tolerability of VUMERITY compared to TECFIDERA in patients with relapsing-remitting MS. In EVOLVE-MS-2, the rate of overall treatment discontinuation was lower in participants treated with VUMERITY compared to those treated with TECFIDERA (1.6% compared to 6%, respectively). The difference in the discontinuation rates due to GI tolerability was 0.8% for VUMERITY compared to 4.8% for TECFIDERA. The improved GI tolerability with VUMERITY translated into clinically meaningful benefits in quality of life, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use.

Smriti: Please tell us more about Biogen’s plans for digital tools to predict MS disease progression. How is it better than the conventional method of detecting MS disease progression?

Monica Mann: Biogen is committed to delivering innovative approaches to reframe the care and treatment of MS, including the development of digital tools to help refine the assessment of disease progression by using cutting-edge computer vision applied to brain magnetic resonance imaging (MRI) scans. In the context of MRI, machine learning has the potential to reveal the pathological state of brain tissue integrity beyond what is visible to the human eye. As such, it augments the information available to neurologists and supports them in assessing the short- and long-term prognosis of patients, rather than substituting their decision-making process. The machine learning algorithm allows identification of subtle patterns of brain MRI signal intensities, which are invisible to the naked eye yet are reflective of a white matter tissue state that precedes new lesion formation. It aims to predict not only future lesion load, but also the spatial distribution of future lesion foci.

Source: Health Central

About Author: Monica Mann is the Vice President, Medical Affairs for Global MS and Pipeline at Biogen. Monica brings 21 plus years of experience in immunology, neurodegenerative, neuropsychiatry and genetic diseases inclusive of small molecules, biologics, and gene therapy. Monica holds a Ph.D. from the Medical College of Wisconsin in CNS inflammation, B cell biology, neuroimmunology and a M.S. in molecular biology from Marquette University

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