BUSINESS: Biogen Plans To Initiate Phase 3b Study Evaluating Potential Benefit Of A Higher Dose Of Nusinersen In Patients Previously Treated With Evrysdi(R) (Risdiplam)

business:-biogen-plans-to-initiate-phase-3b-study-evaluating-potential-benefit-of-a-higher-dose-of-nusinersen-in-patients-previously-treated-with-evrysdi(r)-(risdiplam)
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By Daniel Webster, dWeb.News Publisher

| Source: Biogen Inc.

  • Clinical data available to date suggest there are remaining unmet needs in some spinal muscular atrophy (SMA) patients treated with Evrysdi1-3
  • The ASCEND study aims to evaluate whether treatment with a higher dose of nusinersen has the potential to improve clinical outcomes in these patients
  • Building on the proven efficacy and well-established safety of the currently approved 12-milligram dose, patients in this study will receive an investigational higher dose of nusinersen, which is also being evaluated in the DEVOTE study

CAMBRIDGE, Mass., Sept. 15, 2021 (GLOBE NEWSWIRE) — Biogen Inc. (Nasdaq: BIIB) today announced plans to initiate a global Phase 3b clinical study, ASCEND. The ASCEND study is designed to evaluate the clinical outcomes and assess the safety of a higher dose of nusinersenin children, teens and adults with later-onset spinal muscular atrophy (SMA) following treatment with Evrysdi(r) (risdiplam). People with SMA don’t produce enough survival motor nerve (SMN) protein. This is crucial for maintaining motor neurons that allow them to sit, stand, and move. People with SMA can lose the ability to do everyday tasks such as brushing their teeth, drinking from a cup, and turning on a light switch. 4,5 The goal of treatment in SMA is to sufficiently protect motor neurons and help preserve function.

” We believe that some patients who have been treated with Evrysdi may have had less than optimal outcomes. “The ASCEND study will examine if nusinersen might address this unmet medical need. It will also help inform the future treatment of SMA with the hope to improve patients’ outcomes over the long-term,” stated Maha Radhakrishnan M.D. Chief Medical Officer at Biogen.

Available data suggest that exposure to Evrysdi diminishes with increased age and weight, with an approximately 40 percent reduction in drug concentration in adults compared to infants. 6,7 Evrysdi’s dosing is capped at 5 milligrams (mg) once patients reach 20 kilograms (kg). 8

At the approved 12-mg dose, motor neuron exposure to nusinersen remains similar as patients age and grow. 9 Further, nusinersen has demonstrated proven, sustained efficacy and a well-characterized safety profile, with long-term data in patients treated for more than 7 years across ages and SMA types. These data, taken together, support further investigation of whether a higher dosage can provide greater efficacy for patients. The ASCEND study will examine if nusinersen at higher doses may be able to address clinical needs of patients with SMA who have had their treatment modified. In the ongoing DEVOTE research, the same higher-than-normal dose of nusinersen has been evaluated.

“There have been important advances in SMA treatment. However, there is still no cure. Unmet medical needs remain,” stated Professor Tim Hagenacker from Essen University, Germany. He is also a member the ASCEND steering committee. “As part my clinical practice, I’ve seen an opportunity to potentially improve patient outcomes. With a higher dose of nusinersen, we are positioned to explore what may be possible.”

The ASCEND protocol has been submitted to the U.S. Food and Drug Administration and is planned to be an approximately 2.5-year study projected to enroll up to 135 later-onset, non-ambulatory individuals with SMA (aged 5 to 39). Participants must have received Evrysdi at a maximum dose of 5 mg. They also need to be able and willing to alter their treatment to a higher dose. To be eligible for the study, participants must fall within a specific Revised Upper Limb Module(RULM) measurement range. Individuals enrolled in ASCEND will receive two loading doses of nusinersen 50 mg two weeks apart, followed by a maintenance dose of 28 mg every four months during the study period. RULM will assess efficacy. Safety, Hammersmith Functional Motor Scale Expanded and caregiver burden are other clinical outcomes. The study will also evaluate upper limb fine motor function in participants aged 13 and older using the mobile application Konectom(tm), and neurofilament levels as a marker of biological disease activity, both exploratory endpoints.

The study will include adults, children, and teens who have not been treated with nusinersen before Evrysdi. The company aims for the first eligible patients to be enrolled in 2021.

In addition to ASCEND, as a leader in SMA Biogen supports over 15 SMA disease registries with more than 4,000 patients across the globe, which will help support treatment decisions within the context of currently approved therapies, including the 12-mg dose of nusinersen.

*Nusinersen is currently commercialized under the brand name SPINRAZA(r), and the U.S. Food and Drug Administration-approved dose is 12 mg.

About SPINRAZA(r) (nusinersen)

The SPINRAZA clinical development program encompasses 10 clinical studies, which have included more than 300 individuals across a broad spectrum of patient populations,10 including two randomized controlled studies (ENDEAR and CHERISH). SPINRAZA’s long-term effects are being evaluated by the ongoing SHINE open-label extension trials and NURTURE open label extension studies. In clinical trials, the most common adverse reactions were back pain, fever, constipation and headaches. Some ASOs have caused some ASO-related toxicity in the laboratory.

Biogen has licensed the worldwide rights to develop, manufacture, and market SPINRAZA from Ionis Pharmaceuticals, Inc., (Nasdaq : IONS), a leader in antisense therapeutics. Click here to view Important Safety Information and complete Prescribing Information about SPINRAZA in America. You can also visit the product websites of your country.

About Spinal Muscular Atrophy (SMA)

SMA is a rare, genetic, neuromuscular disease that affects individuals of all ages. This disease is characterised by the loss of motor neurons in lower brain stem and spinal cord, which causes progressive muscle weakness and atrophy. 11 SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missing SMN1 gene, with a spectrum of disease severity. 11 Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time. 12 In the absence of treatment, children with the most severe form of SMA would not be expected to reach their second birthday. 11

SMA impacts approximately 1 in 11,000 live births,13 is a leading cause of genetic death among infants13 and causes a range of disability in teenagers and adults. 12

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen develops, delivers and distributes worldwide innovative therapies to people with neurodegenerative and serious neurological diseases. 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. Biogen is the world’s leading provider of multiple sclerosis medicines. It has also introduced the first treatment for spinal muscular atrophy. Biogen also commercializes biosimilars to advanced biologics. The company’s focus is on research in multiple sclerosis, neuroimmunology and Alzheimer’s disease, neuropsychiatry and immunology.

We regularly post information to our website http://www.biogen.com that might be of interest to investors. Follow us on Twitter, LinkedIn and Facebook.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of nusinersen; the results of certain real-world data; the identification and treatment of SMA; our research and development program for the identification and treatment of SMA; the clinical development program for nusinersen, including the study protocol and enrollment of the ASCEND study and the timing thereof; and risks and uncertainties associated with drug development and commercialization. These statements can be identified using words like “aim”, “anticipate”, “believe,”” “could”, “estimate,”,”forecast,” and “forecast.” The Safe Harbor provisions of the Private Securities Litigation Reform Act of
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act for 2017. These statements and the scientific data presented should not be relied upon.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation risks relating to the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis, including from the planned ASCEND study; the risk that we may not fully enroll our clinical trials, including the planned ASCEND study, or enrollment will take longer than expected; failure to obtain regulatory approvals in other jurisdictions; risks of unexpected costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. These factors could lead to actual results that differ from those in forward-looking statements. This cautionary statement should be considered along with other risk factors that we have identified in our most recent quarterly or annual report and other reports we filed with the U.S Securities and Exchange Commission. These statements reflect our current beliefs and expectations. They are made as of the date this news release.

References: 2020216061Mercuri E. et al.

References:

  1. Mercuri E. et al. SUNFISH Part 2: Efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). SMA Europe Feb 5-7, 2020 presentation.
  2. Evrysdi US FDA Summary Basis of Approval (SBA) documents. Clinical Review(s): Page 67, table 15. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000TOC.cfm. Accessed: September 2021.
  3. European Medicines Agency: EMA/216061/2021 – Evrysdi EPAR. Page 195, table 41. Available at: https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf. Accessed September 2021.
  4. Rouault F, et al. The effects of disease on the general well-being, and expectations for treatment, in European Type II and Type III spinal muscle atrophy patients. Neuromuscul Disord. 2017 May;27(5): 428-438. doi: 10.1016/j.nmd.2017.01.018. Epub 2017 Feb 3.
  5. Mazzone ES, et al. Revision of the upper limb module to treat spinal muscular atrophy: Development a new module. Muscle Nerve. 2017 Jun;55(6): 869-874. doi: 10.1002/mus.25430. Epub 2017 Feb 6.
  6. Evrysdi US FDA SBA documents. Clinical Pharmacology Review(s): Page 41, table 18. The approximately 40% reduction is the percentage difference between risdiplam observed exposures in the youngest infants and adults. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000TOC.cfm. Accessed: September 2021.
  7. European Medicines Agency: EMA/216061/2021 – Evrysdi EPAR. Page 71, figure 13. The approximately 40% reduction is the percentage difference between risdiplam observed exposures in the youngest infants and adults. Available at: https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf. Accessed September 2021.
  8. Evrysdi U.S. Prescribing Information. Available at: https://www.gene.com/download/pdf/evrysdi_prescribing.pdf. Accessed: September 2021.
  9. Finkel RS, et al. Scientific justification for higher doses of Nusinersen. Cure SMA Virtual Research and Clinical Care Meeting June 9-11, 2021 poster presentation.
  10. Core Data Sheet, Version 9, January 2019. SPINRAZA. Biogen Inc, Cambridge, MA.
  11. National Institute of Neurological Disorders and Stroke, NIH. Spinal Muscular Atrophy Fact sheet. Available at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Spinal-Muscular-Atrophy-Fact-Sheet. Accessed: September 2021.
  12. Wadman RI, Wijngaarde CA, Stam M, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. Eur J Neurol. 2018;25(3): 512-518.
  13. Cure SMA. SMA. Available at https://www.curesma.org/about-sma/. Accessed: September 2021.

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