Shots:

• Monica spoke about the data from the NOVA P-IIIb study evaluating the efficacy of its lead candidate in Multiple Sclerosis(MS)
• Monica also talked about the clinical trial results and formulation of the advanced product in MS
• The interview gives a view of Biogen’s developing molecules in the pipeline for MS

Smriti: Can you share with us the insights of data obtained from the NOVA P-IIIb study evaluating TYSABRI (natalizumab) IV dosing Q6W?

Monica Mann: The NOVA trial is the first prospective study evaluating every six-week dosing of natalizumab in patients with relapsing-remitting multiple sclerosis (MS), providing important information about the efficacy of six-week dosing and affirming real-world evidence reports from the clinical community. 

Specifically, data from the NOVA Phase 3b study published in The Lancet Neurology 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 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: Tell us more about TYSABRI and its formulation details.

Monica Mann: TYSABRI (natalizumab) is a well-established treatment indicated for relapsing forms of MS in adults, which has been proven in clinical trials to slow physical disability progression, and reduce the formation of new brain lesions and decrease the rate of MS-related relapses. In the European Union, it is indicated as a single disease-modifying treatment (DMT) in adult patients with relapsing-remitting MS that experience highly active disease activity following a full and adequate course of treatment with at least one DMT or patients with rapidly evolving severe relapsing-remitting MS. TYSABRI can be administered through subcutaneous injection (EU only) or intravenous (IV) infusion, and the approved dose is 300mg every 4 weeks.

Smriti: Explain the epidemiology of multiple sclerosis.

Monica Mann: According to the MS International Federation, 2.8 million people live with MS worldwide, and that number has increased in every world region since 2013.

Smriti: According to your POV, how is IV dosing more beneficial than oral dosing?

Monica Mann: As mentioned above, TYSABRI can be administered by subcutaneous injection or intravenous (IV) infusion.

Smriti: Throw some light on other drugs developing in your pipeline against multiple sclerosis?

Monica Mann: Biogen has pioneered the development of MS treatments for more than 25 years. We continue to innovate to advance MS treatment and improve outcomes for patients. Our research is focused on potentially transformative therapies, including the potential repair of the damage caused by MS. We hope our ongoing research into neurodegeneration and nerve repair will help pioneer new therapeutic solutions that may bring us closer to a cure for MS. 

We currently have exciting drug candidates in our clinical development pipeline, including orelabrutinib (BTK inhibitor), BIIB091 (BTK inhibitor), and BIIB107 (anti-VLA₄) – as well as additional assets in the pre-clinical space. Biogen currently has more than 20 active and ongoing MS clinical trials, for both investigational and existing therapies. While we focus on advancing current assets in our pipeline, we aspire to pioneer disruptive therapies for MS prevention and cure by exploring emerging science including novel treatment approaches such as vaccine cell-based therapies.

Smriti: What are the benefits of Q6W dosing over existing Q4W?

Monica Mann: The NOVA results build upon the retrospective safety analyses of the TOUCH Prescribing Program, which found that extended interval dosing of approximately every six weeks with IV natalizumab is associated with a significantly lower risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection, as compared to the approved every four-week dosing schedule. 

In NOVA, which was designed to assess the efficacy of Q6W dosing with natalizumab IV administration, disease activity was well-controlled in both arms. There was a numerical but not statistically significant difference in the primary efficacy endpoint between the Q4W and Q6W treatment arms, where the mean number of new or newly enlarging T2 hyperintense lesions at week 72 was 0.05 (Q4W) and 0.20 (Q6W) (p=0.0755). There were no statistically significant or clinically meaningful differences in secondary endpoints at week 72 between the Q4W and Q6W treatment arms; annualized relapse rates were low and a similarly high percentage of patients in both arms remained relapse-free. NOVA was not designed to assess the risk of PML.

Smriti: Is Biogen planning to obtain regulatory approval for Q6W dosing? When can expect the same?

Monica Mann: While these data advance our understanding of the efficacy and safety of Q6W natalizumab, TYSABRI 300 mg on a Q4W regimen remains the only approved dosing schedule. In the European Union, the TYSABRI Summary of Product Characteristics (SmPC) was updated in March 2022 to include data on the efficacy of Q6W IV dosing from NOVA while maintaining Q4W as the only approved dosing regimen. We cannot comment on other regulatory actions.

Source: Canva

About the Author: 

Monica Mann is the Vice President of Medical Affairs for Global MS and Pipeline at Biogen. Monica brings 21 plus years of experience in immunology, neurodegenerative, neuropsychiatry, and genetic diseases, including 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 an M.S. in molecular biology from Marquette University

Related Post: PharmaShots Interview: Biogen’s Monica Mann Shares Insights on the New Real-World Data on Tysabri & Vumerity for the Treatment of Multiple Sclerosi