Biogen (NASDAQ:BIIB) executives highlighted progress across several pipeline programs during a discussion that focused on the company’s tau antisense oligonucleotide (ASO) program in Alzheimer’s disease, pre-symptomatic anti-amyloid studies, neuromuscular development in spinal muscular atrophy (SMA), and immunology assets in lupus and kidney diseases.
Tau ASO program: rationale, safety considerations, and the CELIA trial
Diana Gallagher, head of clinical development at Biogen, said the company views tau as an important target in Alzheimer’s disease because tau pathology is closely associated with cognitive decline. She described a hypothesis in the field that amyloid deposition may precede or enable tau pathology to propagate through the brain, with tau changes aligning more closely with cognitive decline.
On safety and biology, Gallagher said tau has critical functions related to neuronal structural integrity, and Biogen’s intention is not to eliminate tau completely. She noted genomic data suggesting that up to a 50% reduction in tau may be associated with no gross neurological effects, and said Biogen has targeted a degree of knockdown intended to test the hypothesis while managing safety. She referenced roughly 60% CSF tau knockdown as being “on the range” observed in the phase 1b study, and said patients are being monitored in both the main trial and a long-term open-label extension.
Gallagher said the phase 1b study evaluated whether the drug affected relevant brain regions and reported reductions in tau PET across multiple areas of the brain. However, she emphasized that the extent and duration of tau lowering needed for clinical efficacy remains unknown and is a key question CELIA is designed to address.
When asked whether CELIA is intended as a p-value-driven decision, Gallagher characterized it as a proof-of-concept study designed for internal decision-making. She said additional evidence would be required beyond CELIA to support registrational ambitions, including expanded safety data and further clarification of dose-response and clinical effects.
Pre-symptomatic Alzheimer’s: AHEAD 3-45 design and the role of diagnostics
Gallagher also discussed Biogen and Eisai’s AHEAD 3-45 study of Leqembi (lecanemab) in pre-symptomatic Alzheimer’s disease. She described AHEAD 45 as enrolling individuals with amyloid burden greater than 40 centiloids, using the PACC5 cognitive endpoint over a four-year period to assess whether treatment can prevent cognitive decline in participants with “low plaque level” who do not yet show clinical cognitive decline. She described AHEAD 3 as enrolling participants with lower amyloid burden (20–30 centiloids) to examine whether treatment can attenuate plaque accumulation.
Gallagher said a positive result from Lilly’s TRAILBLAZER-ALZ 3 would be “great for patients and families,” while noting differences in study design and inclusion criteria. She said a negative readout would need to be examined in context, given differences in endpoints and populations. Asked about effect size expectations, she cited data from open-label extensions in earlier-disease subgroups, saying that in a low- and no-tau group on continuous lecanemab, 70% of patients had no cognitive decline and 50% showed improvement versus baseline at four years, while cautioning that those populations are not directly comparable to the pre-symptomatic AHEAD cohorts.
On feasibility and commercial readiness for treating pre-symptomatic patients, Gallagher pointed to diagnostics as a key enabler, particularly blood-based biomarkers. She said neurologists are increasingly using blood tests to screen and then confirm with imaging, and suggested that more reliance on blood-based testing could streamline the pathway over time. She added that in AHEAD 3-45, using blood-based biomarkers before confirmatory imaging reduced screen-fail rates by 50%. Gallagher also referenced the potential importance of subcutaneous at-home administration and a larger role for primary care physicians, noting that capacity constraints make it difficult to place the burden solely on neurologists.
SMA: salanersen Phase 1b signals and three Phase 3 studies
Stephanie Fradette, head of the Neuromuscular Development Unit, discussed salanersen, an investigational ASO using novel chemistry intended to increase potency and enable once-yearly dosing. She said Biogen’s phase 1b study enrolled individuals who had received gene therapy at least six months prior and were viewed by investigators as having suboptimal clinical status, reflecting unmet need for additional efficacy. The study enrolled two age cohorts (6 months to 2 years, and 2 to 12 years), tested 40 mg and 80 mg doses, and included 24 participants.
Fradette said new data presented at least one year of follow-up across all 24 participants. She said both doses were generally well tolerated and considered plausible for phase 3. She also highlighted biomarker findings: participants entered with elevated neurofilament levels beyond what would be expected in untreated and treated SMA populations, consistent with active neurodegeneration. After initiating salanersen, she said neurofilament levels were reduced rapidly and remained reduced over time.
Fradette said exploratory clinical observations suggested that some patients achieved new developmental milestones after initiating salanersen, including in cases where children were years removed from gene therapy and would not typically be expected to continue improving.
On how salanersen could compare with Spinraza, Fradette said the program is designed to achieve concentrations and efficacy consistent with high-dose Spinraza while extending dosing intervals, but she said definitive conclusions require phase 3 data and noted there has been no direct head-to-head comparison.
Biogen outlined three phase 3 studies:
- STELLAR-1 (pivotal): treatment-naive presymptomatic infants with two or three SMN2 copies, evaluating attainment of sitting (two-copy) and walking (three-copy) within normal developmental timelines.
- STELLAR-2 (supportive): presymptomatically gene-therapy-treated infants randomized six months later to receive salanersen or sham control.
- SOLAR: teens and adults including 60 treatment-naive participants and 30 switching from risdiplam; Fradette noted feedback from the community advocating for a larger risdiplam-treated cohort.
High-dose Spinraza: bridging unmet need and a potential transition path
Fradette said high-dose Spinraza represents Biogen’s effort to optimize an existing therapy as the field recognizes ongoing unmet need despite the transformational impact of first-generation treatments. She cited persistent functional gaps even among presymptomatically treated infants, such as abnormal gait. Fradette said Biogen is working to make high-dose Spinraza available globally and anticipates that many individuals could transition to salanersen if it is approved and available.
Immunology and nephrology: litifilimab, CD40 biology, and Felzartamab
Gallagher addressed investor concerns about lupus trial reproducibility ahead of litifilimab phase 3 data. She said Biogen has pursued BDCA2 biology methodically, from biomarker-heavy early studies to proof-of-concept work, and cited improvements in joint and skin measures and SRI-4 in earlier studies. She emphasized that phase 2 was not designed or powered for the phase 3 endpoint, and said Biogen is conducting two replicate phase 3 SLE trials with 540 patients each powered for SRI-4, alongside work in cutaneous lupus erythematosus (CLE) using the CLASI endpoint. She said new data from the phase 2 portion of the AMETHYST CLE trial will be shared as a late-breaker at the American Academy of Dermatology meeting later in the month, and that the company hopes for registrational SLE data by year-end followed by CLE.
Gallagher also discussed CD40 pathway targeting, referencing a phase 3 in SLE that she described as one of only the third positive phase 3 trials in the disease. She highlighted supportive outcomes including steroid tapering, reduction in flares, and fatigue improvements. On safety concerns historically associated with CD40 ligand programs, she said earlier molecules were believed to activate platelets through Fc-related effects, while Biogen’s molecule was engineered with an Fc-silent Fab fragment and designed to reduce clotting risk beyond the baseline risk associated with lupus.
Finally, Gallagher discussed “Felza” across three phase 3 programs in antibody-mediated rejection (AMR), IgA nephropathy (IgAN), and membranous nephritis (PMN). She singled out AMR as potentially underappreciated, citing 11,000 patients in the U.S. who experience AMR within six months after transplant and describing phase 2 data showing 80% resolution at six months, while noting the need to replicate in phase 3. She also said IgAN could support a differentiated paradigm involving upfront therapy followed by potential “holidays,” and described PMN as another area of significant unmet need.
About Biogen (NASDAQ:BIIB)
Biogen Inc is a multinational biotechnology company focused on discovering, developing and delivering therapies for neurological and neurodegenerative diseases. Headquartered in Cambridge, Massachusetts, the company has a longstanding emphasis on neuroscience, with research and commercial activities spanning multiple therapeutic areas including multiple sclerosis, spinal muscular atrophy and Alzheimer’s disease. Biogen was founded in 1978 and has grown into a global biopharmaceutical firm with operations and commercial presence across North America, Europe, Japan and other international markets.
The company’s marketed portfolio has historically included several well-known therapies for multiple sclerosis such as Avonex, Tysabri and Tecfidera, and it has pursued treatments for rare neurological conditions and genetic neuromuscular disorders.
