Prothena Corporation plc (NASDAQ:PRTA) shared results on Wednesday from the Phase 1 ASCENT clinical program in participants with early symptomatic Alzheimer’s disease (AD).
As previously communicated, Prothena plans to explore potential partnership interest to advance PRX012 and its preclinical PRX012-TfR (transferrin receptor) antibody.
The Phase 1 ASCENT clinical program results demonstrated PRX012 as a potential once-monthly, subcutaneous anti-amyloid beta (Aβ) antibody with stable pharmacokinetics, low anti-drug antibodies, and low injection site reactions, as well as dose- and time-dependent reductions in amyloid plaque.
At the 400 mg dose level, PRX012 demonstrated a mean reduction in amyloid PET to 27.47 centiloids (CL) at month 12; FDA-approved anti-Aβ antibodies have defined amyloid negativity thresholds of ≤30 CL or ≤24.1 CL.
However, PRX012 was associated with higher overall ARIA-E rates relative to FDA-approved anti-Aβ antibodies, making PRX012 less appropriate for the patients studied in the ASCENT clinical program.
When ARIA-E did occur, the characteristics were similar to those reported following treatment with other anti-Aβ antibodies.
At 200 mg and 400 mg doses, 38.1% to 41.7% of patients had amyloid-related imaging abnormality-edema (ARIA-E), a swelling of the brain associated with anti-amyloid beta antibodies.
This compares with Eisai Co Ltd (OTC:ESALY) and Biogen Inc (NASDAQ:BIIB), which previously reported a 13% rate of ARIA-E in a study of Leqembi.
In two Eli Lilly and Co. (NYSE:LLY) studies, 3% and 6% of patients had symptomatic ARIA-E.
Prothena called the ARIA-E profile in early symptomatic Alzheimer's "non-competitive."
Based on the profile observed in the ASCENT clinical program and feasibility work already completed on its preclinical Aβ-transferrin receptor antibody surrogate, Prothena believes this approach may represent an opportunity to significantly reduce the risk of ARIA and quickly decrease amyloid plaque with 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.
Prothena, which initiated a reduction of approximately 63% of its workforce in June, does not plan to share additional data from the ASCENT clinical program publicly. However, it expects to explore potential partnership interests to advance PRX012 and PRX012-TfR.
In May, Prothena’s Phase 3 AFFIRM-AL trial for birtamimab in patients with AL amyloidosis did not meet its primary endpoint (HR=0.915, p-value=0.7680).
Based on these results, the company discontinued the development of birtamimab, including stopping the open-label extension of the AFFIRM-AL trial.
In August, Prothena announced that Novo Nordisk A/S (NYSE:NVO) expects to advance coramitug, a potential first-in-class amyloid depleter antibody, into a Phase 3 program for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in 2025.
Coramitug was initially developed by Prothena and was acquired by Novo Nordisk in July 2021. Prothena is eligible to receive up to $1.2 billion in milestone payments.
Price Action: PRTA stock is down 0.75% at $8.49 at the last check on Thursday.
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