Phase 3 Clinical Trial of Birtmamimab in AL Amyloidosis Fails to Meet Primary Endpoint

BREAKING NEWS: Prothena Corp has announced that the Phase 3 AFFIRM-AL clinical trial evaluating birtamimab in patients with Mayo Stage IV AL amyloidosis has failed to meet its primary endpoint.

This announcement means that treatment with birtamimab did not significantly prolong survival within the duration of the study, based on the data collected and analyzed as part of the study. The company also announced neither of the secondary endpoints were met (6-minute walk test distance and Short Form-36 version 2 Physical Component Score). Birtamimab development will be discontinued, including stopping the open label extension of the AFFIRM-AL clinical trial.

We recognize this is a sad day for the amyloidosis community and encourage you to contact us by phone at 617-467-5170 or by email at support@arci.org for additional support. ARC remains steadfast in our commitment to accelerating the development of new therapies and improving the lives of people living with AL amyloidosis. We will continue to keep you informed about developments in amyloidosis as they become available.

What is AL Amyloidosis?

AL amyloidosis is one of the most common types of amyloidosis and involves proteins called light chains. Light chains make up part of the structure of immunoglobulins (antibodies) which play an important part in the immune system. They are produced by plasma cells in the bone marrow. In AL amyloidosis, abnormal plasma cells make excessive amounts of abnormal light chain proteins. Instead of forming immunoglobulin, they become misfolded and deposit as amyloid in various organs of the body.

What was the AFFIRM-AL Study?

The AFFIRM-AL study was a phase 3 clinical trial evaluating birtamimab, an investigational drug designed to find and stick to amyloid fibrils in patients with AL amyloidosis, prompting the body’s immune system to recognize the amyloid and try to clear it out. AFFIRM-AL was designed to find out if birtamimab works and if it is safe when given with chemotherapy to people who are newly diagnosed with AL amyloidosis and have severe heart involvement (Mayo Stage IV).

The trial, which began in 2021, enrolled 207 patients across more than 140 centers globally. Patients who participated received either the investigational drug and standard of care chemotherapy or placebo (a substance that looks like the investigational drug but has no active drug in it) and standard of care chemotherapy.

What Comes Next

This is a disappointing result, especially for those who participated in the study or were hopeful about its potential. Though the endpoints of the trial were not met, birtamimab was considered generally safe and well-tolerated.

“We share in the disappointment felt across the AL amyloidosis community following the results from the AFFIRM-AL clinical trial. While this trial has failed, we still believe this is an important approach and there is an urgent need for therapies that target removal of amyloid and ultimately restore organ function. We are profoundly grateful to every patient, caregiver, and researcher who participated in this clinical trial and contributed to this important effort. Without willing trial participants, new treatments won’t be possible.”

— Kristen Hsu, Executive Director of Research, ARC

ARC and the amyloidosis community thanks those who participated in this and all clinical trials, which play a vital role in advancing treatment. Each trial, regardless of outcome, provides critical information that helps the entire field move forward. Negative results still teach us valuable lessons about the disease and what’s needed in future drug development efforts.

These negative results mean the end of Prothena’s investigation into birtamimab. Future studies and investigational treatments from other companies will rely on the continued participation of amyloidosis patients and their families.

There are additional drugs that are designed to target and remove amyloid deposits currently being studies in clinical trials for both AL and ATTR amyloidosis. ARC remains steadfast in our committee to accelerating the development of new therapies and improving the lives of people living with AL amyloidosis. We will continue to keep you informed about developments in amyloidosis as they become available.

Read Prothena’s press release here.

Learn about AL amyloidosis here.