Publicerade NURTURE-data lyfter fram motoriska milstolpar hos presymtomatiska spädbarn med SMA som behandlats med SPINRAZA (nusinersen) och ger insikter om mått på sjukdomsaktivitet

• Efter ca fem års nusinersen-behandling av presymtomatiska barn var den motoriska funktionen bibehållen eller förbättrad. 23 av 25 barn gick självständigt och samtliga var vid liv
• Analyser av NURTUREs inklusionskriterier har gett viktiga insikter gällande definitionen av presymptomatisk SMA
• Nya analyser tyder på att små skillnader i baslinjeegenskaper är viktiga att ta hänsyn till vid tolkning av kliniska studier och att dessa kan ge information om förväntade resultat hos SMA-patienter vid tidigt insatt behandling under spädbarnsåren

Upplands Väsby – 18 juli 2023 – Biogen Inc. (Nasdaq: BIIB) announced that Muscle & Nerve has published data from the NURTURE study demonstrating children who initiated SPINRAZA^TM (nusinersen) treatment before the onset of clinical spinal muscular atrophy (SMA) symptoms continue to maintain and achieve new motor milestones over five years. After two additional years of follow-up, all participants are alive, none require permanent ventilation and 23 of 25 children are walking independently, most within age-appropriate timelines. In the context of expanded newborn screening worldwide, the NURTURE data also provide further insights on the emerging importance of objective measures of disease activity that may help to inform therapeutic expectations based on individual patient baselines.

Five-year results from NURTURE show children with three SMN2 copies (n=10) achieved all World Health Organization (WHO) motor milestones¹ within age-appropriate timelines, with the exception of one child who missed the window for walking with assistance but went on to achieve walking alone on time. In children with two SMN2 copies (n=15), all could sit without support and stand with assistance, 14 were able to walk with assistance, and 13 achieved standing alone and walking alone, with some attaining milestones within age-appropriate timelines. Since the prior publication of NURTURE results, two additional patients with two SMN2 copies achieved the maximum Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score at ages 3.8 and 4.8 years, bringing the total to 22 children in the study (12 [80%] with two SMN2 copies; 10 [100%] with three SMN2 copies). No additional children required respiratory intervention as defined per the primary endpoint since the prior data cut, when four were reported.

“The SMA scientific community is recognizing the importance of early markers of neurodegeneration in infants with SMA who appear to be asymptomatic when first evaluated,” said Thomas Crawford, M.D., Co-Director, Muscular Dystrophy Association Clinic and Professor of Neurology at Johns Hopkins. “The NURTURE data show how small differences in baseline characteristics can greatly impact outcomes, including motor function, respiratory function, swallowing and feeding. CMAP amplitude and areflexia are indicators of advancing SMA pathology before the onset of signs or symptoms; these characteristics, and others to be developed, are important for the proper interpretation of data from studies evaluating SMA therapies.”

A post-hoc analysis of the NURTURE data assessed early markers of disease activity, such as baseline compound muscle action potential (CMAP) and areflexia, under the hypothesis that measures of neuronal damage can show disease progression prior to clinical symptom onset. In NURTURE, baseline characteristics were different from other pre-symptomatic SMA studies with inclusion criteria allowing for patients with lower CMAP values (≥1 mV) or who are areflexic. When data from participants with two SMN2 copies who did not meet the criterion of peroneal CMAP ≥2mV or had areflexia were excluded, the reporting of the overall motor and non-motor outcomes in this NURTURE subgroup were better than those of the entire study cohort. This included increased proportions of participants achieving motor milestones within normal developmental timeframes and either no or fewer children with respiratory intervention, gastrostomy tube placement, and SMA symptoms within 24 months.

The safety profile of nusinersen over this extended follow-up period was consistent with previously reported findings. In the study, 12 participants (48%) had one or more serious adverse events (AEs). No AEs or serious AEs were considered to be related to nusinersen treatment. The most common AEs reported in the NURTURE study were pyrexia, upper respiratory tract infection, cough and nasopharyngitis. When analyzed in approximately yearly intervals, the incidence of serious AEs decreased over time.

NURTURE is an ongoing, Phase 2, open-label study of 25 presymptomatic patients with the genetic diagnosis of SMA (considered most likely to develop SMA Type 1 or 2) who received their first dose of nusinersen before 6 weeks old. The study is evaluating the longer-term efficacy and safety of nusinersen through 8 years of age to further understand the impact of early treatment. More information on the NURTURE study (NCT02386553) is available on clinicaltrials.gov.

About SPINRAZA^TM (nusinersen)
Nusinersenis approved in more than 60 countries to treat infants, children and adults with spinal muscular atrophy (SMA). As a foundation of care in SMA, more than 14,000 individuals have been treated with nusinersenworldwide.²

Nusinersen is an antisense oligonucleotide (ASO) that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.³ It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.³

Nusinersen has demonstrated efficacy across ages and SMA types with an established safety profile based on data in patients treated up to 8 years,⁴ combined with real-world experience. The nusinersen clinical development program encompasses more than 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations, including two randomized controlled studies (ENDEAR and CHERISH). The SHINE and NURTURE open-label extension studies are evaluating the long-term impact of nusinersen. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs.

Biogen licensed the global rights to develop, manufacture and commercialize nusinersenfrom Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for nusinersen in the U.S., or visit your respective country’s product website.

Nusinersen är avsett för behandling av spinal muskelatrofi av typ 5q. Hos patienter som behandlats med nusinersen genom lumbalpunktion har allvarlig infektion, såsom meningit, observerats. Det har även förekommit rapporter om kommunicerande hydrocefalus, aseptisk meningit och överkänslighet (t.ex. angioödem, urtikaria och hudutslag). För information om kontraindikationer, varningar och försiktighet, biverkningar, dosering och förpackningar se http://www.fass.se.

About Biogen

Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.

We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Twitter, LinkedIn, Facebook, YouTube.

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; our research and development program for the identification and treatment of SMA; clinical development programs, clinical trials and data readouts and presentations; the potential benefits and results from treatment of SMA; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements or the scientific data presented.

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 NURTURE studies; the risk that we may not fully enroll our clinical trials, 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. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References:

1. WHO Multicentre Growth Reference Study Group. WHO Motor Development Study: Windows of achievement for six gross motor development milestones. Acta Paediatr Suppl. 2006 Apr;450:86-95. doi: 10.1111/j.1651-2227.2006.tb02379.x.
2. Based on commercial patients, early access patients, and clinical trial participants through December 31, 2022. 
3. SPINRAZA U.S. Prescribing Information. Available at: https://www.spinraza.com/content/dam/commercial/specialty/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf. Accessed: June 2023.
4. Tulinius M, et al. Long-Term Safety and Efficacy of Nusinersen in Infantile-Onset Spinal Muscular Atrophy: 5-Year Interim From SHINE. Poster PC22. Presented at SMA Europe 3^rd International Scientific Congress on Spinal Muscular Atrophy, October 21–23, 2022, Barcelona, Spain.

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Biogen-215613 July 2023