Biogen’s BIIB080 Exhibits Favorable Outcomes in Phase 1b Trial for Early Alzheimer Disease


Patients with mild Alzheimer disease who received high doses of BIIB080 demonstrated improvement in cognitive and functional outcomes compared with placebo, supporting further investigation.

Priya Singhal, MD, MPH, head of development at Biogen

Priya Singhal, MD, MPH

New data from the phase 1b trial (NCT03186989) assessing BIIB080 (Biogen), an investigational antisense oligonucleotide (ASO) therapy targeting tau, showed numerical differences favoring the therapy in high-dose groups on multiple cognitive and functional scales at completion of the multiple ascending dose (MAD) and long-term extension (LTE) in patients with mild Alzheimer disease (AD).1 These findings support further investigation of BIIB080’s potential clinical efficacy and safety in patients with mild cognitive impairment (MCI) because of AD or mild AD in the ongoing CELIA phase 2 trial (NCT05399888).2

The data showed differences in baseline clinical scores between treated groups, low-dose groups and high-dose groups, compared with the pooled placebo. At week 37, end of the MAD, favorable differences were reported in the high-dose groups on the Mini-Mental State Exam (MMSE) cognitive scales and Functional Activities Questionnaire (FAQ), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scales compared with the placebo. Notably, in the low-dose groups, unfavorable group averages were observed relative to the placebo.

“This is the first time we’ve seen both strong target engagement and favorable trends on clinical outcomes with a novel mechanism targeting tau,” Priya Singhal, MD, MPH, head of development at Biogen, said in a statement.1 “While these are preliminary findings, we are excited about these results and continue to enroll the phase 2 CELIA study. We believe defeating AD will take different approaches and we are committed to exploring the targeting of tau as a new generation of treatment.”

Clinical Takeaways

  • BIIB080, an investigational therapy targeting tau in patients with mild Alzhiemer disease (AD), shows promise in improving cognitive and functional outcomes.
  • High-dose groups of BIIB080 demonstrated positive trends in cognitive and functional scales, supporting further clinical investigation in the ongoing CELIA phase 2 trial.
  • While it should be cautiously interpreted because of the small sample size, these findings suggest a potential new avenue in the treatment of AD by targeting tau protein.

The findings were presented at the 2023 Clinical Trials on Alzheimer Disease (CTAD) conference, held October 24-27, held in Boston, Massachusetts, by senior author Melanie Shulman, MD, MPhil, the senior medical director of the Alzheimer's Disease and Dementia Research Unit at Biogen, and colleagues. In the trial, 46 participants were randomly assigned to placebo or to 4 dose cohorts: 10 mg, 30 mg, or 60 mg dosed once every 4 weeks, or 115 mg dosed every 12 weeks. The high-dose groups (60 mg, 115 mg) in the MAD transitioned to the LTE seamlessly, and low-dose groups (10 mg, 30 mg) had variable gaps between 5 and 19 months. The primary end point was safety and the key exploratory clinical outcomes assessed included MMSE, FAQ, RBANS, and Clinical Dementia Rating Sum of Boxes (CDR-SB).

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In the LTE, baseline characteristics were similar between BIIB080-treated groups and matched external controls. The investigators noted that a favorable trend was observed on the CDR-SB, MMSE and FAQ at week 100, the end of the LTE, compared with the matched external controls in participants who received high doses. They also noted that mixed results were observed across the clinical scales in patients who switched from low dosage in the MAD to high dosage in the LTE.

All told, all treatment-emergent adverse events (AEs) in both the MAD and LTE were mild to moderate in severity except for 1 AE of severe pain in lower extremity. The authors reported that the most common AEs were headache, back pain, extremity pain, post-lumbar puncture syndrome, and procedural pain. Only 8 serious AEs were reported, and none were assessed in relation to the study treatment or study procedure. No deaths were reported in the study; thus suggesting that the treatment was generally well tolerated. In addition, the authors noted that caution should be considered during interpretation of the results because of the small sample size and use of external controls in the LTE.

“We believe these new data represent an important step in our effort to both optimize patient outcomes with current treatments while simultaneously advancing the next wave of breakthroughs in AD,” Singhal said in an earlier statement.3 “We’ve reached a potential tipping point in this complex field and remain determined to continue moving forward with the community to help the millions of people impacted by AD.”

These results build on data presented at the 2023 International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD), held March 28-April 1, in Gothenburg, Sweden, which showed a reduction of soluble tau protein in cerebrospinal fluid (CSF) with treatment of BIIB080 in patients with early AD.4 The results showed that BIIB080 reduced biomarkers of soluble tau in CSF (t-tau and p-tau181) in a dose-dependent and sustained manner. By the end of the LTE, all dose groups showed approximately a 60% reduction from baseline CSF tau levels. Notably, BIIB080 also reduced aggregated tau pathology as early as week 25 and up until the end of the LTE at week 100, including patients who started on placebo and were given BIIB080 at week 25 in the LTE.

Recruitment for the phase 2 CELIA study of BIIB080 is ongoing at sites across North America, Europe, and Asia–Pacific for patients with MCI or mild dementia because of AD.1 Researchers will investigate if BIIB080 can slow the worsening of AD more than placebo and what dosage of the treatment shows the most efficacy in slowing the worsening of AD. The CDR-SB will be used to measure dementia symptoms, and those enrolled will be given a low dose or high dose of BIIB080 or a placebo as an injection into the fluid around the spinal cord. Participants will be in the study for 105 weeks, which includes the time for screening and follow-up periods.

Click here for more coverage on CTAD 2023.

1. New Data from Biogen’s Investigational Antisense Oligonucleotide (ASO) Targeting Tau Shows Promise for Potential New Generation of Treatments in Early Alzheimer’s Disease. News Release. Published October 25, 2023. Accessed October 26, 2023.
2. Ziogas N, Wu S, Li Y, et al. Exploratory clinical outcomes from BIIB080 (MAPT ASO) Phase 1b multiple ascending dose and long-term extension study in mild Alzheimer’s disease. Presented at: CTAD Conference 2023; October 24-27; Boston, MA. LB09.
3. Biogen to Present New Data at the Clinical Trials on Alzheimer’s Disease (CTAD) 2023 Meeting. News Release. Published October 19, 2023. Accessed October 26, 2023.
4. New data presented at AD/PD™2023 show IONIS-MAPT Rx (BIIB080) substantially reduced tau protein in patients with early-stage Alzheimer's disease. News Release. Biogen. Published March 29, 2023. Accessed October 26, 2023.
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