Biogen and Ionis report positive topline clinical data on investigational Alzheimer’s disease treatment at AAIC

Biogen. Inc. and Ionis Pharmaceuticals, Inc. announced that topline data from a Phase 1b placebo-controlled, multiple ascending dose clinical study showed that BIIB080/IONIS-MAPTRx met its primary objective of safety and tolerability in patients with mild Alzheimer’s disease. The study demonstrated robust time and dose-dependent lowering of tau protein in cerebrospinal fluid (CSF) over the three-month treatment period and sustained reductions during the six-month post-treatment period.

In patients receiving BIIB080, there were dose-dependent decreases in the concentration of total-tau in CSF eight weeks post-last dose (Day 141) with a mean percentage reduction of 30 percent, 40 percent and 49 percent in the low, medium and high dose groups treated every four-weeks, respectively, and 42 percent in the group treated every 12 weeks. Total-tau in the CSF continued to decline 16 weeks post-last dose in patients treated with BIIB080 in the high dose four-week and 12-week dose groups, showing a 55 percent and 49 percent mean reduction from baseline, respectively. CSF was not collected 16 weeks post-last dose in the low and medium four-week dose groups. There were similar dose-dependent decreases in the levels of phosphorylated tau. All participants (n=46) completed the Multiple Ascending Dose (MAD) period and 43 participants completed the Post-Treatment (PT) period (3 participants voluntarily withdrew). These data were presented in a poster session at the 2021 Alzheimer’s Association International Conference (AAIC) held virtually and in Denver, Colo., July 26 – 30.

“There is clearly an urgent need to develop and deliver effective treatments for Alzheimer’s disease, a devastating disorder for which there currently are limited therapeutic options. We are encouraged by the topline results from this study of BIIB080, which demonstrate the potential of Ionis’ antisense technology to successfully target what we believe is a root cause of Alzheimer’s disease,” said C. Frank Bennett, Ph.D., Ionis’ chief scientific officer and franchise leader for neurological programs. Dr. Bennett added, “These study results support further investigation of BIIB080 for the treatment of Alzheimer’s disease and suggest that antisense-mediated suppression of tau protein may be a feasible therapeutic approach for other tauopathies.”

“Biogen is deeply committed to the development of novel treatments for patients with Alzheimer’s disease. This commitment extends across multiple modalities, including antisense oligonucleotides, as with BIIB080,” said Alfred Sandrock, Jr., M.D., Ph.D., Head of Research and Development at Biogen. “Biogen is encouraged by the results of this trial, and we look forward to our continued research in future clinical studies with this promising investigational asset.”

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive and functional decline resulting in significant disability. Until recently, treatment was limited to management of symptoms. BIIB080 is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) mRNA and prevent production of tau protein. Growing evidence suggests that aggregated, hyperphosphorylated tau may be a key driver of neurodegeneration in Alzheimer’s disease as well as other tauopathies including progressive supranuclear palsy and frontotemporal degeneration. In preclinical studies in MAPT transgenic mice, MAPT-targeted antisense treatment demonstrated robust tau-lowering in CNS tissues and prevention and reversal of disease.

The primary objective of the Phase 1b first-in-human study was to assess safety and tolerability of multiple intrathecal (IT) bolus administrations of BIIB080. The study was divided into two parts: Part 1, a MAD study of 46 patients with mild Alzheimer’s disease comprising a three-month Treatment Evaluation Period and a six-month PT period; Part 2, an open label long-term extension study comprising a 12-month Treatment Evaluation Period and a four- or six-month PT period. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to IT bolus administrations of BIIB080 or placebo. Patients aged 50-74 years with mild Alzheimer’s disease and confirmed amyloid positivity (via CSF) at screening were considered eligible. Part 1 is now complete; Part 2 is currently ongoing (EudraCT: 2016-002713-22; NCT03186989).

The characteristics of patients at baseline were representative of relatively younger, mild Alzheimer’s disease patients and were generally similar across trial groups. All adverse events were mild to moderate in severity with no serious adverse events occurring in any patients that received BIIB080. There were no deaths, dose-limiting adverse events or dosing discontinuations.