Author: admin

• Approval is supported by data from the DEVOTE study which showed the benefit of the SPINRAZA 50 mg and 28 mg regimen in both treatment-naïve and previously-treated nusinersen patients with SMA¹
• Biogen is dedicated to partnering with the SMA community to advance care through scientific innovation and a commitment to enhancing outcomes for people living with SMA

CAMBRIDGE, Mass., Jan. 12, 2026 (GLOBE NEWSWIRE) — Biogen Inc. (Nasdaq: BIIB) today announced the European Commission (EC) has granted marketing authorization for a high dose regimen of SPINRAZA^® (nusinersen) which is comprised of 50 mg/5 mL and 28 mg/5 mL doses for the treatment of 5q spinal muscular atrophy (SMA). 5q SMA is the most common form of the disease and represents approximately 95% of all SMA cases.² The SPINRAZA European Union marketing authorization has been updated to include the high dose regimen. The new high dose regimen comprises a more rapid loading phase, two 50 mg loading doses administered 14 days apart and 28 mg maintenance dose injections every four months thereafter. Individuals transitioning from the 12 mg dose will receive one 50 mg dose in place of their next 12 mg dose, followed by 28 mg maintenance doses every four months thereafter. SPINRAZA is for intrathecal use by lumbar puncture by health care professionals experienced in performing lumbar punctures.

“Since its approval in the European Union in 2017, SPINRAZA has helped set a new standard in patient care and treated more than then 10,000 infants, children, teens and adults worldwide,” Priya Singhal, M.D., M.P.H., Executive Vice President and Head of Development at Biogen. “We are proud to introduce the high dose regimen of SPINRAZA, which we have developed to address the evolving needs of individuals living with SMA, and are deeply committed to bringing it to the European SMA community as quickly as possible. We are grateful for all of the contributions of the SMA community who made today’s approval possible.”

The EC approval is based on data from the three-part, Phase 2/3 DEVOTE study and its ongoing long-term extension. Results from the pivotal cohort of the study showed treatment-naïve, symptomatic infants who received the high dose regimen of SPINRAZA experienced statistically significant improvements in motor function as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), when compared to a prespecified matched sham (untreated) group from the ENDEAR study* (mean difference: 26.19 points; +15.1 vs. -11.1, p<0.0001). Improvements in motor function were also observed in the open label cohort of individuals across a broad range of ages and SMA types who transitioned from the low dose regimen. These participants experienced a mean improvement on the Hammersmith Functional Motor Scale – Expanded of 1.8 points [SD 3.99] from baseline to Day 302.¹

“The DEVOTE results provide encouraging evidence that this new dosing option could deliver meaningful treatment outcomes with a safety profile generally consistent with the 12 mg dosing regimen,” said Eugenio Mercuri, M.D., Ph.D., Professor of Pediatric Neurology at the Catholic University, Rome, Italy. “I have witnessed the remarkable strides that have been made in treating SMA, but it is clear challenges remain. The European Commission approval of the high dose regimen of SPINRAZA is an important step toward addressing those challenges and advancing how we care for people living with SMA.”

Throughout the study, high dose regimen was generally well tolerated, with reported adverse events consistent with SMA and the known safety profile of nusinersen. No new safety concerns were observed with continued use of high dose nusinersen in the long-term-extension study. In the DEVOTE study, the most common adverse events that occurred in at least 10% of participants treated with the high dose regimen and occurred at least 5% more frequently than the matched sham group were pneumonia, COVID-19, pneumonia aspiration, and malnutrition.¹

Special warnings and precautions for use of nusinersen include adverse reactions as a part of the lumbar puncture procedure, low platelet counts and blood clotting abnormalities, renal toxicity and hydrocephalus (excessive buildup of cerebrospinal fluid in the brain).³

“As a community, we welcome advances that expand options for people living with SMA and reinforce continued innovation in SMA care,” said Nicole Gusset, CEO of SMA Europe. “This approval highlights the importance of sustained research and investment, contributing to a wider range of possibilities that may enable more tailored approaches to SMA care over time.”

The updated Summary of Product Characteristics will be available on the European Medicines Agency website at www.ema.europa.eu. 

The high dose regimen of SPINRAZA is also approved in Japan and is under review with the U.S. Food and Drug Administration (FDA) with a decision expected by April 3, 2026. Biogen is working with regulatory authorities around the world to progress this additional dosing option for people living with SMA. 

*ENDEAR is one of the two pivotal studies that formed the basis of regulatory approvals for SPINRAZA 12 mg.

About the DEVOTE Study¹
DEVOTE was a Phase 2/3 randomized, controlled, dose-escalating study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of SPINRAZA 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 included 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 high 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).

About SPINRAZA
The high dose regimen of SPINRAZA (nusinersen) which is comprised of 50 mg/5 mL and 28 mg/5mL injections are approved in the European Union and Japan to treat infants, children and adults with spinal muscular atrophy (SMA). The high dose regimen of nusinersen is currently under review with the U.S. Food and Drug Administration (FDA) with a decision expected by April 3, 2026. SPINRAZA 12 mg/5 mL injection is approved for SMA in more than 71 countries.⁴

The low dose regimen of SPINRAZA has shown efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 10 years,^5,6 combined with unsurpassed real-world experience. 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). For more information, visit your respective country’s product website. For the U.S., please click here for Important Safety Information and full Prescribing Information .

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, among others, relating to: the potential benefits, efficacy and safety of higher doses of nusinersen (marketed as SPINRAZA); the potential to improve outcomes for, and address unmet needs of, patients with SMA; potential regulatory discussions, submissions, decisions and approvals and the timing thereof; the anticipated benefits, risks and potential of our collaboration arrangements; the potential of our commercial business and pipeline programs, including nusinersen; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “goal,” “guidance,” “hope,” “intend,” “may,” “objective,” “outlook,” “plan,” “possible,” “potential,” “predict,” “project,” “prospect,” “should,” “target,” “will,” “would” or the negative of these words or 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 these statements. Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements.

These forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to differ materially from those stated or implied in this document, including, among others, uncertainty of our long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans, prospects and timing of actions relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; the potential impact of increased product competition in the biopharmaceutical and healthcare industry, as well as any other markets in which we compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our corporate strategy; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks related to commercialization of biosimilars, which is subject to such risks related to our reliance on third-parties, intellectual property, competitive and market challenges and regulatory compliance; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; and the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in reports we have filed with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at www.sec.gov.

These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise.

Digital Media Disclosure
From time to time we have used, or expect in the future to use, our investor relations website (investors.biogen.com), the Biogen LinkedIn account (linkedin.com/company/biogen-) and the Biogen X account (https://x.com/biogen) as a means of disclosing information to the public in a broad, non-exclusionary manner, including for purposes of the SEC’s Regulation Fair Disclosure (Reg FD). Accordingly, investors should monitor our investor relations website and this social media channel in addition to our press releases, SEC filings, public conference calls and webcasts, as the information posted on them could be material to investors.

References:

1. Crawford TO, et al. Exploring Higher Doses of Nusinersen in Spinal Muscular Atrophy: Final Results From Parts B and C of the 3-Part DEVOTE Study. Presented at: World Muscle Society (WMS) Congress; 2024; Prague, Czechia.
2. Farrar MA, Kiernan MC. The Genetics of Spinal Muscular Atrophy: Progress and Challenges. Neurotherapeutics; 2015; 12:290–302.
3. European Medicines Agency. SPINRAZA Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/spinraza-epar-product-information_en.pdf. Last accessed: December 2025.
4. Based on commercial patients, early access patients, and clinical trial participants through December 31, 2022. 
5. Core Data sheet, Version 13, October 2021. SPINRAZA. Biogen Inc, Cambridge, MA.
6. Finkel RS, et al. Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile-Onset and Later-Onset SMA. Presented at: Cure SMA Conference; 2024; Austin, Texas.

We thus collect all the parameters estimated from the data in a vector $\mathit{\pi }=(h,q_d,q_0,K)$. As we will better detail in the Methods, we develop a moment matching inference algorithm to infer the model parameters $\mathit{\theta }$, as depicted in Figure 1. The idea of the method is to introduce a cost function $\mathcal{C}(\mathit{\theta }|\mathit{\pi })$, representing a total relative error for some self-consistent equations. If the parameters $\mathit{\theta }$ are such that the right part of the self-consistent equation equals the left part, the problem is considered solved. Because the landscape associated with this cost function presents several minima, we perform multiple optimization procedures to collect an ensemble of possible solutions, from which we retain the top 30. First, we find that different solutions ${\mathit{\theta }}^{\ast }$ of the optimization problem provide ecological insights into the underlying microbiome populations.

As originally predicted in Altieri et al., 2021, among all the parameters that define Equation 1, the only ones relevant for reproducing the theoretical phase diagram are the amplitude of demographic noise and the heterogeneity of interactions. The mean interaction strength, provided it is sufficiently positive, does not play a significant role. This prediction is fully confirmed by the inference procedure applied to the two microbiome datasets, allowing us to identify a universal signature that distinguishes healthy from unhealthy states. Figure 3a shows, indeed, that inferred noise ($T$) and interaction heterogeneity strength ($\sigma$) for healthy and diseased microbiomes are clustered in the two-dimensional plane.

In particular, the SAD for the healthy cohort is robust among the different solutions of the inference procedure, as depicted by the superposition of the different curves in the inset of Figure 3a. On the other hand, SADs inferred from unhealthy patients have high sensitivity to different solutions. In particular, some of them display a mode for high-abundance species (light red lines in Figure 3a), a signature of dominant strain in the gut. Consistently, the distribution of the interactions $P({\alpha }_{i,j})$ generated through the inferred parameters μ and σ is different between healthy and diseased cohorts, giving a distinct pattern of interactions (see Figure 3b), a result that is compatible with that found by Bashan et al., 2016. Remarkably, we find that dysbiosis reduces the heterogeneity of interaction strengths, a result also observed when taking correlations as a proxy for interactions (Seppi et al., 2023).

We then assess how close the inferred σ and $\beta =1/T$ (a.k.a. inverse temperature in a statistical physics approach) are to the critical RSB line of the dgLV ($\mathcal{R}=0$), evaluated by keeping all the other parameters constant (see Methods). We find again that the replicon values $\mathcal{R}$ corresponding to each solution of our optimization protocol are significantly different for the two investigated microbiome phenotypes (see Figure 4a). In particular, diseased microbiomes are closer to marginal stability within the RS ansatz (Altieri et al., 2021; Mézard et al., 1987; de Almeida and Thouless, 1978). Furthermore, by investigating the shape of the SAD given by Equation 2, we can estimate the ratio between niche (represented by species interaction) and neutral (represented by birth/death and immigration) ecological forces, which can be captured by the quantity $\psi$ (Wu et al., 2021). It detects the emergence of peaks in the SAD as a hallmark of niche processes (see Appendix 2).

Inspired by field-theory arguments (see Methods and Appendix, Section S2), we can call the mass of the theory the $m$ parameter, as defined above in Equation 2. In classical and quantum field theory, the particle–particle interaction embedded in the quadratic term is typically referred to as a mass source. In our context, $m=1-\beta {\sigma }^2(q_d-q_0)$ captures quadratic fluctuations of species abundances, as also appearing in the expression of the leading eigenvalue of the stability matrix. When $m\to 0$, the analytical order parameters diverge and the system enters the unphysical regime of unbounded growth. As such, the mass term can be considered a complementary stability measure, capable of capturing the transition to the unbounded growth regime.

In the model, two kinds of effects compete to shape the community structure. On the one hand, we have niche effects, encoded in disordered interactions and thus tracked by the parameters μ, σ, and $K$. Their overall effect is selective and tends to concentrate the SAD around the typical abundance value. On the other hand, we have neutral effects encoded in the stochastic dynamics and immigration, governing the low-abundance regime of the SAD. When the demographic noise amplitude is stronger than immigration ($\nu <1$, as in our case), the SAD exhibits a low-abundance integrable divergence. In the opposite scenario, for $\nu >1$, there is no divergence, and the SAD is modal. Since interactions are random, the probability of observing an internal mode can be estimated as the fraction of SADs realizations having non-trivial solutions to the stationary point equation. Such a quantity, dubbed as the niche–neutral ratio, can be analytically evaluated:

(5)

${\displaystyle {\displaystyle {\displaystyle \psi =\frac{1}{2}\text{Erfc}\left(\frac{{\zeta }^{\ast }+\overline{\zeta }}{\sqrt{2}{\sigma }_{\zeta }}\right)+\frac{1}{2}\text{Erfc}\left(\frac{{\zeta }^{\ast }-\overline{\zeta }}{\sqrt{2}{\sigma }_{\zeta }}\right),}}}$

where ${\zeta }^{\ast }=\sqrt{\frac{4(1-\nu )m}{\beta }}$ and $\overline{\zeta }=K-\mu h$. When $\psi \approx 1$, niche and neutral forces give comparable contributions to the dynamics, as both low-abundance divergence and a finite abundance mode coexist in the SAD. Finally, if the typical abundance diverges, we enter the unbounded growth phase, which means that the mass $m$ and the niche–neutral ratio $\psi$ are not independent, as suggested by the analytical expression for $\psi$. For an exhaustive derivation of this result, see Appendix 2. With the obtained model parameters, we are able to evaluate $m$ and $\psi$ for healthy and diseased microbiomes. Also, in this case, healthy and diseased microbiomes are visibly clustered, as shown in Figure 4. Unhealthy microbiomes turn out to be closer to the unbounded growth phase, and the niche–neutral ratio is larger by five orders of magnitude than the healthy case ${\psi }_D\approx {10}^5{\psi }_H$. This leads us to argue that selective pressure is way larger in diseased states, while in the healthy one, birth and death effects are the key drivers of the dynamics. These results are also confirmed by the SAD shapes in the inset of Figure 3 (panel a).

In summary, in the Results section, we show that (i) the inference pipeline robustly recovers demographic noise and interaction heterogeneity by calculating $h$, $q_0$, and $q_d$ from the data; and (ii) these parameters cluster according to health status, with diseased microbiomes lying closer to the replica-symmetry-breaking threshold, indicating reduced ecological resilience.