Prothena Looks at Business Options as Phase III AL Amyloidosis Trial Fails

 

Prothena has already discontinued the development of birtamimab, and anticipates further spending cuts, including workforce reduction.

Prothena’s anti-amyloid antibody birtamimab missed its primary endpoint in the Phase III AFFIRM-AL trial, unable to significantly improve time to all-cause mortality in patients with AL amyloidosis, the biotech announced on Friday. Birtamimab also failed to hit its key secondary endpoints.

The late-stage stumble appears to have sent Prothena into crisis mode. Daniel Welch, chair of the company’s board of directors, said on Friday that Prothena’s board and management “have begun the work to thoughtfully and expeditiously decrease spend . . . and evaluate with its financial advisors business options in the best interest of its shareholders.”

These options, Welch noted, include an “expected substantial workforce reduction.” Prothena on Wednesday also discontinued the development of birtamimab, including terminating the open-label extension phase of AFFIRM-AL. The company will provide more details regarding the strategic review in June.

In a note to investors early on Tuesday, Jefferies analysts called the Phase III failure “disappointing but not surprising,” noting that birtamimab had previously failed a late-stage study.

Prothena had previously tested birtamimab in the Phase III VITAL study, enrolling 260 newly diagnosed patients with AL amyloidosis who had not yet undergone treatment. The study was discontinued in April 2018 for futility. Full data, released a year later, confirmed that birtamimab did not significantly increase time to all-cause mortality or cardiac hospitalization.

Indeed, in an April 20 note, more than a month ahead of Friday’s readout, Jefferies warned investors that AFFIRM-AL is “very high-risk, high-reward” for the company. The odds were stacked against Prothena, according to Jefferies’ analysis, which estimated a 25% to 30% chance of success. “We are at best cautiously optimistic,” the analysts wrote at the time.

Prothena is “disappointed” by the results of AFFIRM-AL, Welch said on Friday, however noting that the company “has meaningful data readouts and pipeline updates over the next 18 months.” In August, he continued, Prothena is set to report early-stage data for its once-monthly subcutaneous antibody PRX012 in Alzheimer’s disease, while updates for respective programs partnered with Roche and Novo Nordisk will come in the next few months. Updates for an unnamed collaboration with Bristol Myers Squibb are expected next year.

In the first quarter of 2025, Prothena reported a net loss of $60.2 million, lower than its $72.2 million deficit during the same period a year prior. As of March 31, the company had $418.8 million in cash, cash equivalents and restricted cash with no debt.

https://www.biospace.com/drug-development/prothena-looks-at-business-options-as-phase-iii-al-amyloidosis-trial-fails