Prothena Reports Phase 1 ASCENT Clinical Program Results for PRX012, Exploring Partnerships to Advance Alzheimer's Treatment

Prothena Corporation has released results from the Phase 1 ASCENT clinical program for PRX012, an anti-amyloid beta antibody for early Alzheimer's disease. The trial demonstrated potent amyloid plaque reduction, but PRX012 showed a higher rate of ARIA-E compared to existing treatments. Prothena is exploring partnerships to advance PRX012 and its preclinical antibody PRX012-TfR.

Prothena Corporation plc (NASDAQ: PRTA) has announced results from the Phase 1 ASCENT clinical program for PRX012, an anti-amyloid beta antibody designed to treat early Alzheimer's disease. The trial, conducted in participants with early symptomatic AD, demonstrated that PRX012 is a potential once-monthly, subcutaneous anti-amyloid beta antibody with stable pharmacokinetics and low anti-drug antibodies. At the 400 mg dose level, PRX012 showed a mean reduction in amyloid plaque to 27.47 centiloids (CL) at month 12, compared to baseline levels of 75.47 CL [1].

However, the trial also revealed that PRX012 was associated with higher overall ARIA-E rates relative to FDA-approved anti-Aβ antibodies, making it less suitable for the patients studied in the ASCENT clinical program. ARIA-E (amyloid-related imaging abnormalities - edema) is a known side effect of anti-Aβ antibodies. When ARIA-E did occur, its characteristics were similar to those reported following treatment with other anti-Aβ antibodies.

Prothena believes that the profile observed in the ASCENT clinical program and the feasibility work completed on its preclinical Aβ-transferrin receptor antibody surrogate may represent an opportunity to significantly lower the risk of ARIA and quickly reduce amyloid plaque with a once-monthly subcutaneous administration. Initial preclinical studies have demonstrated substantially increased brain exposure and facilitated rapid targeting of Aβ plaques in an APP/PS1 transgenic mouse model.

Chad Swanson, Ph.D., Chief Development Officer, Prothena, expressed appreciation for the dedication and collaboration of patients, families, investigators, and staff in achieving the objectives of the Phase 1 ASCENT clinical program. He noted that Prothena plans to explore potential partnership interest to further develop PRX012 and its preclinical antibody PRX012-TfR.

The Phase 1 ASCENT clinical program included three trials: ASCENT-1, ASCENT-2, and ASCENT-3. The objectives were to determine the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012. The ASCENT-2 and ASCENT-3 trials also evaluated the pharmacodynamics of PRX012, including amyloid plaque deposition as measured by positron emission tomography (PET).

PRX012 was generally well-tolerated across all dose cohorts of the trial. Injection site reactions were low, and treatment emergent anti-drug antibodies were low and generally transient. There was one death in the study, in the 45 mg dose cohort, which was determined by the investigator to be not related to study drug.

Prothena does not plan to publicly share additional data from the ASCENT clinical program while it expects to explore potential partnership interest to advance PRX012 and PRX012-TfR.

References:
[1] https://www.biospace.com/press-releases/prothena-provides-update-on-prx012-and-announces-results-from-the-phase-1-ascent-clinical-program