#AAIC21 – BIIB080 Safely Lowered Tau Levels in Patients in Phase 1 Trial

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by Forest Ray PhD |

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BIIB080, an investigational therapy for Alzheimer’s disease, was safe and well-tolerated, and sustainably lowered patients’ levels of tau — a protein linked to neurodegeneration, according to topline results of a Phase 1b clinical trial.

“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,” C. Frank Bennett, PhD, Ionis’ chief scientific officer, said in a press release.

Ionis Pharmaceuticals originally developed BIIB080, under the name IONIS-MAPTRx, which it licensed to Biogen for further development in late 2019.

“We are encouraged by the topline results from this study of BIIB080,” Bennett added, “which demonstrate the potential of Ionis’ antisense technology to successfully target what we believe is a root cause of Alzheimer’s disease.”

BIIB080 is a DNA-like molecule called an antisense oligonucleotide. It is designed to be compatible with the messenger RNA (mRNA) that carries the instructions for making the tau protein. By binding to that mRNA, BIIB080 prevents it from being used to produce tau.

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Biogen and Ionis presented trial results in a poster session at the 2021 Alzheimer’s Association International Conference, held virtually and in Denver, Colorado, in late July.

The two-part Phase 1 study (NCT03186989) primarily sought to assess the medication’s safety and tolerability, given as an infusion directly into the spinal canal.

Secondary goals included measuring various pharmacological properties of BIIB080.

In part 1, which is now complete, 46 patients with mild Alzheimer’s and confirmed amyloid tau buildup were randomized to either ascending doses of BIIB080 or a placebo for three months, and then evaluated at six months post-treatment. Part 2, which is ongoing, is an open-label extension study, with 12 months of treatment given to all followed by a four- or six-month evaluation period.

Participants in part 1 given BIIB080 saw dose-dependent drops in total tau levels in their cerebrospinal fluid, or CSF, eight weeks following their last dose. This fluid bathes the brain and spinal cord, cushioning those organs from injury and serving as a means to deliver nutrients to, and remove waste from, the brain.

Low, medium, and high doses — given every four weeks — corresponded to declines in tau levels of 30%, 40%, and 49%, respectively. A separate group being treated once every 12 weeks experienced a mean drop in tau protein of 42%.

Participants in the 12-week group and those in the high-dose, four-week group continued to see their tau levels decline by a mean of 49% and 55%, respectively, 16 weeks following their last dose. Investigators did not collect CSF at the 16-week mark for those in the low- and medium-dose groups.

Phosphorylated tau — a form of the protein that strongly correlates with neurodegeneration — also declined in a similar dose-dependent manner.

All 46 people completed the randomized and double-blind treatment phase of part 1, and 43 finished the six-week evaluation that followed. Three patients voluntarily withdrew, the release reported. Part 2 is due to conclude in May 2022.

“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,” Bennett stated.

Adverse side effects were mild to moderate in severity. No serious adverse effects occurred in patients receiving BIIB080. No deaths, dose-limiting adverse reactions, or dosing discontinuations occurred.

“Biogen is encouraged by the results of this trial,” said Alfred Sandrock, Jr., MD, PhD, Biogen’s head of research and development, “and we look forward to our continued research in future clinical studies with this promising investigational asset.”