The company has, as such, initiated a Phase 1 single ascending dose (SAD) study to investigate the safety, tolerability, immunogenicity, and pharmacokinetics of that antibody in both healthy volunteers and patients with AD. In the Phase 1 SAD study, healthy volunteers and patients will be randomized to receive a single subcutaneous injection of either PRX012 or placebo.
Prothena said it expects to initiate the Phase 1 multiple ascending dose study by the end of 2022.
PRX012, said the company, is a next-generation, high binding potency antibody, designed to enable subcutaneous dosing on a patient-friendly, convenient administration schedule
Prothena’s chief medical officer, Dr Hideki Garren, told this site last July, following a presentation at the 2021 Alzheimer’s Association International Conference (AAIC), that the antibody “has been shown to have 11 times higher binding affinity than the approved treatment, aducanumab, in side by side experiments. So, therefore, we think it should have higher efficacy, and potential safety, as well as convenience for patients [compared to other anti-Aβ therapies].
“But what is really innovative is that PRX012 can clear both pyroglutamate-modified and -unmodified Aβ plaque.”
Such clearance was seen, he said, in brain tissue at concentrations that can be reached in the central nervous system (CNS) with subcutaneous administration, potentially enable greater patient accessibility and compliance relative to approved therapies and treatments currently under development.
Investigational AD vaccine
Prothena has an active vaccine in its portfolio also that it says has the potential to generate a response to both the amyloid beta and the tau proteins. “We think this is a really interesting candidate, not just for treating patients with disease, but also in terms of thinking of secondary prevention type trials. And, down the line, if we had success there, we could think about primary prevention trials, the ultimate goal,” commented Prothena CEO, Gene Kinney, when speaking to BioPharma-Reporter in November 2021.
The company presented new preclinical data at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2022), in Barcelona, Spain, earlier this month, in relation to that investigational vaccine.
“Our dual Aβ/tau vaccine demonstrated, in a preclinical setting, simultaneous generation of antibodies against Aβ and tau with the proper quantity and quality of response, while avoiding engagement of cytotoxic immune responses.
“We continue to build momentum toward our ultimate goal of eradicating Alzheimer’s disease and plan for an IND for this AD vaccine candidate in 2023,” commented Wagner M Zago, CSO, Prothena.
