Prothena Corporation plc (NASDAQ:PRTA) announced today that its Phase 3 AFFIRM-AL clinical trial evaluating birtamimab in patients with AL amyloidosis failed to meet its primary endpoint of time to all-cause mortality. Following these disappointing results, the company will discontinue all development of birtamimab, including the ongoing open-label extension trial.
The global, double-blind, placebo-controlled study enrolled 207 newly diagnosed, treatment-naïve patients with Mayo Stage IV AL amyloidosis. Statistical analysis revealed the trial did not achieve statistical significance for its primary endpoint with a hazard ratio of 0.915 and p-value of 0.7680.
"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 of Prothena.
Trial Design and Secondary Endpoints
The AFFIRM-AL trial administered birtamimab to patients in the active arm every 28 days at a dose of 24 mg/kg, with a maximum dose cap of 2500 mg. Both active and control arms received a bortezomib-containing chemotherapy regimen as standard of care, with daratumumab use permitted.
Secondary endpoints also failed to show significant improvement, including:
- 6-minute walk test distance (nominal p-value=0.5288)
- Short Form-36 version 2 Physical Component Score (nominal p-value=0.9597)
Despite the negative efficacy outcomes, birtamimab maintained its established safety profile and was generally well-tolerated throughout the trial.
Corporate Restructuring Ahead
In response to this setback, Prothena has announced plans to substantially reduce its organizational size and decrease ongoing operating expenses. The company's board has begun evaluating business options with financial advisors to protect shareholder interests.
"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. "The Company and board have begun the work to thoughtfully and expeditiously decrease spend, including but not limited to an expected substantial workforce reduction."
Prothena expects to provide detailed plans for operational expense reductions in June 2025, with further updates on business strategy to follow once analysis and planning are complete.
Pipeline Focus Shifts
Despite this setback, Prothena highlighted several upcoming milestones in its development pipeline:
- Initial data from the Phase 1 ASCENT clinical trials of PRX012 for Alzheimer's disease expected in August 2025
- Program updates from partner Roche expected mid-year 2025
- Updates from Novo Nordisk collaboration expected in second half of 2025
- Bristol Myers Squibb partnership updates anticipated in 2026
About AL Amyloidosis
AL amyloidosis is a rare, life-threatening disease caused by misfolded immunoglobulin light chain proteins that form amyloid deposits in vital organs. These deposits disrupt normal organ function, particularly affecting the heart and kidneys. Mayo Stage IV represents the most advanced form of the disease with significant cardiac involvement and poor prognosis.
Current treatment approaches for AL amyloidosis focus on eliminating the plasma cells producing the misfolded light chains, typically using chemotherapy regimens that may include bortezomib and daratumumab. Birtamimab represented a different approach, targeting the amyloid deposits directly.
About Prothena
Prothena Corporation plc is a clinical-stage biotechnology company specializing in protein dysregulation with a pipeline focused on neurodegenerative and rare peripheral amyloid diseases. The company's research centers on neurological dysfunction and the biology of misfolded proteins.
The company's remaining pipeline includes programs for ATTR amyloidosis with cardiomyopathy, Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions, developed both independently and through partnerships with major pharmaceutical companies.
