Prothena Announces Phase 3 AFFIRM-AL Clinical Trial for Birtamimab in Patients with AL Amyloidosis Did Not Meet Primary Endpoint

Prothena Corporation plc (NASDAQ:PRTA) today announced the Phase 3 AFFIRM-AL clinical trial evaluating 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 will discontinue the development of birtamimab, including stopping the open label extension of the AFFIRM-AL clinical trial.

“This is not the outcome that we expected, and we are surprised and disappointed by these results for patients, their families and caregivers, and for the entire AL amyloidosis community,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “With these results, we believe that the most appropriate action is to discontinue all development of birtamimab. Prothena would like to thank all of the patients, their families and caregivers, and the investigators, site staff and Prothenians that made this clinical trial possible.”

In the Phase 3 AFFIRM-AL clinical trial, the primary endpoint of time to all-cause mortality was not met for patients treated with birtamimab. In addition, neither of the secondary endpoints were met: 6-minute walk test distance (nominal p-value=0.5288) and Short Form-36 version 2 Physical Component Score (nominal p-value=0.9597). Birtamimab was generally safe and well-tolerated, consistent with its established safety profile.

“While we are all disappointed with today’s results, Prothena has meaningful data readouts and pipeline updates over the next 18 months,” said Daniel G. Welch, Chair of Prothena’s Board of Directors. “We look forward to initial data from the Phase 1 ASCENT clinical trials on PRX012 in Alzheimer’s disease expected in August, and program updates from our partners at Roche expected mid-year, Novo Nordisk expected in 2H25, and Bristol Myers Squibb expected in 2026. The Company and board have begun the work to thoughtfully and expeditiously decrease spend, including but not limited to an expected substantial workforce reduction, and evaluate with its financial advisors business options in the best interest of its shareholders.”

In June, the Company expects to provide details of plans to reduce ongoing operating expenses. The results of the Company’s review of its business options will be communicated as appropriate once the analysis and plans are finalized.

About the Phase 3 AFFIRM-AL Clinical Trial

The Phase 3 AFFIRM-AL clinical trial was a global, double-blind, placebo-controlled, time-to-event clinical trial that enrolled 207 newly diagnosed, treatment naïve patients with Mayo Stage IV AL amyloidosis. Birtamimab was given to the active arm every 28 days at a dose level of 24 mg/kg (maximum dose not to exceed 2500 mg). Patients in both the active and control arms received a bortezomib-containing chemotherapy regimen as standard of care, and use of daratumumab was allowed.