Prothena reports ‘positive’ topline Phase 1 study results for PRX005

Prothena Corporation announced positive topline Phase 1 single ascending dose (SAD) study results for PRX005, a potentially best-in-class investigational tri-epitopic antibody for the treatment of Alzheimer’s disease that specifically binds with high affinity to the R1, R2, and R3 repeats within the microtubule binding region (MTBR) of tau and targets both 3R and 4R tau isoforms. PRX005 is one of three programs in the global neuroscience research and development collaboration between Prothena and Bristol Myers Squibb. "For the first time, we have confirmation that PRX005 is safe and well-tolerated in humans and that it crosses the blood-brain barrier with robust central nervous system (CNS) penetration. We developed PRX005 to uniquely target a key region within the MTBR of tau to reduce pathogenic tau uptake into neurons, an attribute that has not been similarly achievable with antibodies targeting other regions of tau. These topline Phase 1 data, together with the mounting scientific evidence suggesting that tau propagation could be mediated by MTBR-tau seeds, underscores the potential of PRX005 in treating Alzheimer’s disease," said Gene Kinney, PhD, President and Chief Executive Officer of Prothena. "Working closely with Bristol Myers Squibb, we are combining our expertise to advance the development of PRX005 as quickly as possible, and we look forward to seeing Phase 1 multiple ascending dose (MAD) results in patients with Alzheimer’s disease later this year." In this first-in-human, randomized, placebo controlled, SAD study, healthy volunteers (n=19) were enrolled into three PRX005 dose level cohorts (low, medium or high dose) and randomized in a 3:1 drug to placebo ratio. Study participants received a single dose of PRX0005 or placebo intravenously (IV) and were followed for up to two months. The results of the study found all three dose level cohorts of PRX005 to be generally safe and well tolerated, meeting the Phase 1 SAD study primary objective. None of the treatment emergent adverse events (TEAE) were serious. No clinically relevant changes were observed in other safety parameters. PRX005 also met key pharmacokinetic (PK) and immunogenicity secondary endpoints. Plasma drug concentrations of PRX005 increased in a dose-proportional manner. Furthermore, PRX005 exposure in cerebrospinal fluid (CSF) was measured in the high dose cohort and based on the robust exposure of PRX005 in the CSF (day 29 CSF:Plasma ratio=0.2%), substantial target engagement is expected in the CNS. PRX005 had a desirable immunogenicity profile with no persistent PRX005-induced antidrug antibodies (ADAs) observed.