Prothena Discontinues Birtamimab Development After Phase 3 Failure, Plans Substantial Layoffs

Prothena Corporation has announced the discontinuation of its anti-amyloid antibody birtamimab following disappointing results from a phase 3 clinical trial in AL amyloidosis. The company now faces significant organizational restructuring, including substantial workforce reductions.

Phase 3 Trial Results and Program Termination

The confirmatory phase 3 trial, which enrolled 207 newly diagnosed, treatment-naïve patients with Mayo Stage IV AL amyloidosis, failed to meet its primary endpoint of improved all-cause mortality. Patients were randomized to receive either birtamimab or placebo every 28 days, in addition to a standard chemotherapy regimen based on bortezomib. The study also allowed for the use of Johnson & Johnson's anti-CD38 antibody, Darzalex.

Both secondary endpoints were also missed, with birtamimab showing no significant effect on the six-minute walk test or an assessment of physical health. This comprehensive failure has led Prothena to terminate all development activities related to birtamimab.

Historical Context and Previous Setbacks

This marks the second time Prothena has halted development of birtamimab, formerly known as NEOD001. The drug previously failed a phase 2b trial in AL amyloidosis in 2018, which led to the early termination of an ongoing phase 3 study and resulted in a 57% reduction in Prothena's workforce.

The program was resurrected in 2021 following a post-hoc analysis that suggested a survival benefit in a subset of high-risk patients. However, the latest trial results have definitively closed the door on birtamimab's development for AL amyloidosis.

Corporate Restructuring and Financial Implications

In response to the trial failure, Prothena has announced plans for a "substantial reduction in organizational size." The company, which reported 163 employees at the end of December, is set to provide detailed information about the planned cuts next month.

Daniel Welch, chair of Prothena's board of directors, stated that the company has begun "evaluating with its financial advisors business options in the best interest of its shareholders." The results of this review will be shared once the analysis and plans are finalized.

As of March 2023, Prothena reported cash reserves of $418.8 million and had projected to end the year with $301 million under its pre-trial failure spending plan. The company's most advanced wholly owned asset is now PRX012, an Alzheimer's disease candidate with initial phase 1 data expected in August.

While this setback is significant, Prothena maintains partnerships with major pharmaceutical companies, including Bristol Myers Squibb, Novo Nordisk, and Roche, for other pipeline assets. The coming months will be crucial as the company navigates this challenging period and reassesses its strategic direction in the competitive landscape of rare disease therapeutics.