FDA grants Prothena fast track designation for Alzheimer’s disease therapy

03-May-2022 - Last updated on 05-Oct-2022 at 11:38 GMT

Prothena has been granted fast track designation from the US Food and Drug Administration (FDA) to develop a next-generation treatment for Alzheimer’s disease, PRX012.

The Dublin, Ireland headquartered developer said the investigational amyloid beta (Aβ) targeting therapy is currently being investigated in a Phase 1 clinical study for the treatment of Alzheimer’s disease (AD).

The FDA’s fast track designation program is designed to expedite the development and review of drugs intended to treat a serious condition, with evidence demonstrating the potential to address an unmet medical need.

“With its substantially higher binding strength that allows for simple subcutaneous administration, PRX012 is positioned to potentially lead a paradigm shift in Alzheimer’s treatment,” said Prothena CEO, Gene Kinney.

The drug is designed to enable subcutaneous dosing on a patient-friendly, convenient administration schedule

Preclinical data have demonstrated binding of PRX012 to beta amyloid plaques and oligomers with high avidity, allowing effective Aβ plaque occupancy at relatively lower dose ranges, optimal for subcutaneous delivery, said the company.

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 PRX012 “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.

Prothena’s Alzheimer’s disease (AD) portfolio targets two clinical pathways: Aβ and tau.

Along with PRX012, it is developing PRX005, an anti-tau antibody, in conjunction with Bristol-Myers Squibb (BMS), specifically targeting an area within the microtubule binding region (MTBR) for the potential treatment of AD.

AD targeted vaccine

It is also developing a single vaccine that concurrently targets amyloid beta and tau for a mass-immunization to prevent and eradicate AD. “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 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 year, 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.