Prothena's Phase III AL Amyloidosis Trial Failure Prompts Strategic Review

Prothena Corporation, a biotechnology company focused on protein dysregulation and cell adhesion, has announced the failure of its Phase III AFFIRM-AL trial for birtamimab, an anti-amyloid antibody developed for the treatment of AL amyloidosis. The trial's primary endpoint of improved time to all-cause mortality was not met, leading to significant implications for the company's future direction.

Trial Results and Immediate Actions

The AFFIRM-AL trial, which evaluated birtamimab in patients with AL amyloidosis, failed to demonstrate a significant improvement in time to all-cause mortality. Additionally, the drug did not meet its key secondary endpoints. In response to these disappointing results, Prothena has taken immediate action by discontinuing the development of birtamimab, including the termination of the open-label extension phase of the AFFIRM-AL trial.

Daniel Welch, chair of Prothena's board of directors, stated that the company is "disappointed" by the trial's outcome. However, he emphasized that Prothena "has meaningful data readouts and pipeline updates over the next 18 months," indicating that the company is not without future prospects.

Strategic Review and Cost-Cutting Measures

In light of the trial failure, Prothena's board and management have initiated a comprehensive strategic review to address the company's future direction. This review includes plans to "thoughtfully and expeditiously decrease spend" and evaluate various business options that would best serve shareholder interests.

One of the most significant outcomes of this review is the anticipation of a "substantial workforce reduction." While specific details of the layoffs have not been disclosed, this move signals a major restructuring effort to conserve resources and realign the company's focus.

Prothena has announced that it will provide more detailed information regarding its strategic review in June, giving stakeholders a clearer picture of the company's path forward.

Financial Position and Future Outlook

Despite the setback, Prothena maintains a relatively stable financial position. As of March 31, 2025, the company reported $418.8 million in cash, cash equivalents, and restricted cash, with no debt. In the first quarter of 2025, Prothena posted a net loss of $60.2 million, an improvement from the $72.2 million deficit reported during the same period in the previous year.

Looking ahead, Prothena has highlighted several potential catalysts that could influence its future trajectory. In August, the company plans to report early-stage data for PRX012, a once-monthly subcutaneous antibody being developed for Alzheimer's disease. Additionally, updates on programs partnered with Roche and Novo Nordisk are expected in the coming months, with further news on a collaboration with Bristol Myers Squibb anticipated next year.

These upcoming milestones may provide Prothena with opportunities to demonstrate the value of its pipeline and partnerships, potentially offsetting some of the negative impact from the birtamimab trial failure.