Prothena has buried birtamimab for the second time. A phase 3 trial of the anti-amyloid antibody in the rare disease AL amyloidosis missed its primary endpoint, prompting the biotech to end development and plan a “substantial reduction in organizational size.”
Birtamimab, then called NEOD001, failed a phase 2b trial in AL amyloidosis back in 2018. The flop triggered an early look at phase 3 data by the data monitoring committee, which advised Prothena to stop the study because it was destined to fail. Prothena responded by ending all development of birtamimab and, a few months later, by laying off 57% of its employees.
Yet, in 2021, Prothena resurrected the program in response to a post hoc analysis of the phase 3 study. The analysis linked birtamimab to significant improvement in all-cause mortality in a subset of high-risk patients. Prothena started a new phase 3 trial to confirm the survival signal.
The confirmatory phase 3 trial flopped. Investigators randomized 207 newly diagnosed, treatment naïve patients with Mayo Stage IV AL amyloidosis—the high-risk subtype in the post hoc analysis—to receive birtamimab or placebo every 28 days. Patients in both arms received a chemotherapy regimen based on bortezomib and were allowed to receive Johnson & Johnson’s anti-CD38 antibody Darzalex.
Time to all-cause mortality was statistically no better on birtamimab than placebo, causing the trial to miss its primary endpoint. Prothena missed both secondary endpoints, too, with birtamimab having no significant effect on the six-minute walk test and an assessment of physical health.
Responding to the clean sweep of failures, the biotech stopped development of birtamimab and outlined plans to cut costs, including by reducing its head count. Prothena plans to provide details of its cuts next month. The biotech had 163 employees at the end of December.
Daniel Welch, chair of Prothena’s board of directors, said in a statement that the company has begun to “evaluate with its financial advisors business options in the best interest of its shareholders.” Prothena will share the results of the review “as appropriate once the analysis and plans are finalized.”
The company had $418.8 million at the end of March and, under its pre-flop spending plan, expected to end the year with $301 million. Prothena has other readouts coming up, but its most advanced assets after birtamimab are partnered with Bristol Myers Squibb, Novo Nordisk and Roche. Initial phase 1 data on PRX012, Prothena’s most advanced wholly owned asset, in Alzheimer’s disease are due in August.