FDA and EMA Accept Applications for Higher Dose Regimen of Nusinersen in SMA
Biogen (BIIB) announced that both the FDA and EMA have accepted applications for a higher dose regimen of nusinersen for treating spinal muscular atrophy (SMA). The new proposed regimen includes a faster loading schedule with two 50 mg doses given 14 days apart, followed by 28 mg maintenance doses every 4 months. This is an increase from the currently approved SPINRAZA® dosing of 12 mg, which is available in over 71 countries.
The applications are supported by data from the DEVOTE study, which demonstrated potential benefits of the higher dose regimen while maintaining a safety profile consistent with the current 12 mg dosing. The development represents Biogen's ongoing commitment to advancing treatment options for SMA patients.
Biogen (BIIB) ha annunciato che sia la FDA che l'EMA hanno accettato le domande per un regime a dose più alta di nusinersen per il trattamento dell'atrofia muscolare spinale (SMA). Il nuovo regime proposto include un programma di caricamento più rapido con due 50 mg di dosi somministrate a 14 giorni di distanza, seguite da 28 mg di dosi di mantenimento ogni 4 mesi. Questo rappresenta un aumento rispetto al dosaggio attualmente approvato di SPINRAZA®, che è disponibile in oltre 71 paesi.
Le domande sono supportate da dati dello studio DEVOTE, che ha dimostrato i potenziali benefici del regime a dose più alta mantenendo un profilo di sicurezza coerente con l'attuale dosaggio di 12 mg. Lo sviluppo rappresenta l'impegno continuo di Biogen nel migliorare le opzioni terapeutiche per i pazienti affetti da SMA.
Biogen (BIIB) anunció que tanto la FDA como la EMA han aceptado solicitudes para un régimen de dosis más alta de nusinersen para el tratamiento de la atrofia muscular espinal (AME). El nuevo régimen propuesto incluye un esquema de carga más rápido con dos dosis de 50 mg administradas con 14 días de intervalo, seguidas de dosis de mantenimiento de 28 mg cada 4 meses. Esto representa un aumento con respecto a la dosificación actualmente aprobada de SPINRAZA®, que está disponible en más de 71 países.
Las solicitudes están respaldadas por datos del estudio DEVOTE, que demostraron beneficios potenciales del régimen de dosis más alta mientras se mantiene un perfil de seguridad consistente con la dosificación actual de 12 mg. Este desarrollo representa el compromiso continuo de Biogen para avanzar en las opciones de tratamiento para los pacientes con AME.
Biogen (BIIB)은 FDA와 EMA가 척수 근육 위축(SMA) 치료를 위한 nusinersen의 고용량 요법에 대한 신청서를 수락했다고 발표했습니다. 새로 제안된 요법은 두 50 mg 용량을 14일 간격으로 투여한 후, 28 mg 유지 용량을 4개월마다 투여하는 더 빠른 로딩 스케줄을 포함합니다. 이것은 현재 승인된 SPINRAZA®의 12 mg 투여량에서 증가된 것입니다. 이 약물은 71개국 이상에서 사용 가능합니다.
신청서는 DEVOTE 연구의 데이터를 바탕으로 하며, 이는 안전성 프로파일을 유지하면서도 고용량 요법의 잠재적 이점을 입증했습니다. 이 개발은 SMA 환자를 위한 치료 옵션을 발전시키려는 Biogen의 지속적인 노력을 나타냅니다.
Biogen (BIIB) a annoncé que la FDA et l'EMA ont accepté des demandes pour un régime à dose plus élevée de nusinersen pour le traitement de l'atrophie musculaire spinale (AMS). Le nouveau régime proposé comprend un calendrier de chargement plus rapide avec deux doses de 50 mg administrées à 14 jours d'intervalle, suivies de doses d'entretien de 28 mg tous les 4 mois. Cela représente une augmentation par rapport à la posologie actuellement approuvée de SPINRAZA®, qui est disponible dans plus de 71 pays.
Les demandes sont soutenues par des données de l'étude DEVOTE, qui ont démontré les bénéfices potentiels du régime à dose plus élevée tout en maintenant un profil de sécurité cohérent avec la posologie actuelle de 12 mg. Ce développement représente l'engagement continu de Biogen à faire progresser les options de traitement pour les patients atteints de SMA.
Biogen (BIIB) gab bekannt, dass sowohl die FDA als auch die EMA Anträge für ein höher dosiertes Regime von nusinersen zur Behandlung der spinalen Muskelatrophie (SMA) angenommen haben. Das neu vorgeschlagene Regime umfasst einen schnelleren Ladezeitplan mit zwei 50 mg Dosen, die im Abstand von 14 Tagen verabreicht werden, gefolgt von 28 mg Erhaltungsdosen alle 4 Monate. Dies stellt eine Erhöhung gegenüber der derzeit genehmigten SPINRAZA®-Dosierung von 12 mg dar, die in über 71 Ländern erhältlich ist.
Die Anträge werden von Daten aus der DEVOTE-Studie unterstützt, die potenzielle Vorteile des höher dosierten Regimes zeigten, während ein Sicherheitprofil beibehalten wurde, das mit der aktuellen Dosierung von 12 mg übereinstimmt. Diese Entwicklung stellt Biogens kontinuierliches Engagement dar, die Behandlungsoptionen für SMA-Patienten voranzutreiben.
- FDA and EMA acceptance of applications for higher dose regimen indicates regulatory progress
- Current product (SPINRAZA) has established presence in 71+ countries
- DEVOTE study showed meaningful clinical benefits with consistent safety profile
- None.
Insights
The acceptance of Biogen's applications for a higher-dose nusinersen regimen marks a pivotal advancement in SMA therapeutics. The proposed regimen represents a 133% increase in maintenance dosing (from 12mg to 28mg) and introduces an accelerated loading phase with two 50mg doses. This strategic modification could address several critical aspects of SMA treatment:
From a clinical perspective, the higher dosing strategy could potentially enhance drug penetration into the central nervous system, leading to improved efficacy. The DEVOTE study's positive safety profile, despite significantly increased dosing, is particularly noteworthy as it could expand the therapeutic window for SMA treatment.
The market implications are substantial. SPINRAZA, as the first FDA-approved SMA therapy, faces increasing competition from newer treatment options including Novartis's Zolgensma and Roche's Evrysdi. This higher-dose formulation could serve as a important lifecycle management strategy, potentially:
- Reinforcing SPINRAZA's position in an increasingly competitive market
- Providing a new patent protection window
- Offering improved clinical outcomes that could help maintain market share
For investors, this development carries particular significance as it demonstrates Biogen's commitment to protecting and potentially expanding its SMA franchise, which has been a substantial revenue generator. The regulatory validation by both FDA and EMA simultaneously suggests strong clinical data and could accelerate the path to potential approval in major markets.
Applications are based on data from the DEVOTE study, which demonstrate the potential for the investigational higher dose regimen of nusinersen to advance the treatment of SMA
CAMBRIDGE, Mass., Jan. 23, 2025 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) and the European Medicines Agency (EMA) has validated the application for a higher dose regimen of nusinersen for spinal muscular atrophy (SMA). The higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and higher maintenance regimen, 28 mg, every 4 months, compared to the approved nusinersen regimen (SPINRAZA®).
“We are pleased to announce that our applications for the higher dose regimen of nusinersen are now under review in the US and Europe,” said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen. “This milestone reflects our steadfast commitment to advance treatment options for individuals with SMA, and we expect that this higher dose regimen will offer meaningful benefits to patients and their families. We are deeply thankful for the unwavering support of the trial participants, their families, site staff, and the SMA community without whom these advancements would not have been possible.”
Nusinersen is currently commercialized under the brand name SPINRAZA in over 71 countries at the label-approved dose of 12 mg.
“Continued progress to improve upon the remarkable initial successes in SMA necessitates an innovative approach,” said Thomas Crawford, M.D., co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine. “Today’s announcement is a significant step forward for the community. Results from the DEVOTE study have shown us that the higher dose regimen of nusinersen can enable meaningful clinical benefits while maintaining a safety profile broadly consistent with the approved 12 mg regimen.”
About the DEVOTE Study
DEVOTE was a Phase 2/3 randomized, controlled, dose-escalating study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of nusinersen when administered at a higher dose (50/28 mg). The study enrolled 145 participants across ages and SMA types at approximately 42 sites around the world. DEVOTE includes an open-label safety evaluation cohort (Part A), a double-blind, active control randomized treatment cohort (Part B), followed by an open-label treatment cohort (Part C) to assess the safety and tolerability of transitioning participants from the currently approved dose of SPINRAZA 12 mg to the higher dose regimen being tested in the study.
Part B was comprised of a pivotal cohort in treatment-naïve patients with infantile-onset SMA (n=75), and a supportive cohort in treatment-naïve patients with later-onset SMA (n=24). The primary endpoint of Part B measured the change from baseline on CHOP-INTEND at six months comparing the higher dose regimen of nusinersen to a matched, untreated sham control group from the Phase 3 ENDEAR study. ENDEAR is one of the two pivotal studies that formed the basis of regulatory approval for SPINRAZA 12 mg.
Part C was an open-label evaluation of the higher dose regimen in children and adults who transitioned from SPINRAZA 12 mg to the 50/28 mg regimen (n=40).
More information about the DEVOTE study (NCT04089566) is available at clinicaltrials.gov.
About SPINRAZA
SPINRAZA is approved in more than 71 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 SPINRAZA worldwide.1 The currently approved 12 mg regimen for SPINRAZA is comprised of four loading doses administered over approximately 60 days, followed by maintenance dosing every four months thereafter.
SPINRAZA is an antisense oligonucleotide (ASO) that targets the underlying cause of motor neuron loss by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.2 It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.2
SPINRAZA has shown sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 10 years,3,4 combined with unsurpassed 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 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 SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country’s product website.
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Facebook, LinkedIn, X, YouTube.
Biogen Safe Harbor
This news release contains forward-looking statements, including related to the potential clinical effects of a higher dose regimen of nusinersen; the potential benefits, safety and efficacy of higher dose regimen of nusinersen; the clinical development program for higher dose regimen of nusinersen; the identification and treatment of SMA; our research and development program for the treatment of SMA; the potential of our commercial business and pipeline programs, including SPINRAZA; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on our forward-looking statements.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of higher dose regimen of nusinersen; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including SPINRAZA; the occurrence of adverse safety events; the risks of unexpected hurdles, 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; product liability claims; 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 speak only as of the date of this news release.
We do not undertake any obligation to publicly update any forward-looking statements.
References:
- Based on commercial patients, early access patients, and clinical trial participants through December 31, 2022.
- 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: September 2024. - Core Data sheet, Version 13, October 2021. SPINRAZA. Biogen Inc, Cambridge, MA.
- Finkle et al. Cure SMA 2024. “Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile-Onset and Later-Onset SMA.”
| MEDIA CONTACT: Biogen Jack Cox + 1 781 464 3260 public.affairs@biogen.com | INVESTOR CONTACT: Biogen Tim Power +1 781 464 2442 IR@biogen.com |
FAQ
What is the new proposed dosing regimen for BIIB's nusinersen compared to current SPINRAZA dosing?
How many countries currently have approved BIIB's SPINRAZA for SMA treatment?
What clinical trial supports BIIB's application for higher dose nusinersen?
What regulatory agencies are reviewing BIIB's application for higher dose nusinersen?
