Biogen and Ionis Pharmaceuticals have reported that their experimental drug, BIIB080 (IONIS-MAPT), met the primary goal of safety and tolerability in the Phase Ib multiple ascending dose (MAD) clinical trial in mild Alzheimer’s disease patients.
An antisense treatment, BIIB080 potentially targets microtubule-linked protein tau (MAPT) messenger RNA (mRNA) and hinders tau protein production.
The placebo-controlled, two-part Phase Ib trial enrolled patients aged 50 to 74 years with confirmed amyloid positivity.
The first part was a MAD study that involved 46 subjects while the second open-label long-term extension part is underway.
Subjects were enrolled into four ascending dose arms and randomised in a 3:1 ratio to receive various intrathecal (IT) bolus administrations of BIIB080 or placebo.
Top-line data from the trial showed that BIIB080 offered a strong time and dose-reliant decline in tau protein in cerebrospinal fluid (CSF) over a treatment period of three months and lasting decreases during the six months after treatment.
Subjects receiving low, medium and high BIIB080 dose every four weeks had a mean reduction of 30%, 40% and 49%, respectively, in the total-tau concentration in CSF eight weeks after the last dose of the drug.
The group receiving the treatment every 12 weeks had a 42% mean reduction in the total-tau concentration.
Total-tau reductions in the CSF were consistent for 16 weeks after the last dose, with subjects receiving a high dose of BIIB080 every four weeks and 12 weeks experiencing a 55% and 49% mean decrease from baseline, respectively.
Biogen noted that dose-dependent decline in the levels of phosphorylated tau, which may be a major driver of neurodegeneration in Alzheimer’s, was observed.
The severity of all the adverse events (AEs) reported in the trial was mild to moderate without any serious AEs linked to BIIB080.
Ionis Pharmaceuticals chief scientific officer and neurological programmes franchise leader C Frank Bennett said: “We are encouraged by the top-line 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.
“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.”
In April, Ionis initiated a Phase III trial of antisense medicine ION363 in patients with amyotrophic lateral sclerosis (ALS) with mutations in the fused in sarcoma gene (FUS).