Today, World Amyloidosis Day, we recognize people living with AL amyloidosis and their caregivers for their unwavering strength. We recently sat down with Ingrid Sprinz, PhD, Senior Medical Director, Hematology, to speak about current needs in the treatment of AL amyloidosis and Prothena’s progress in the space. Check out her perspective below.

 

Q: What is AL amyloidosis and how does it usually present itself in patients?

A: AL amyloidosis is a rare, progressive, life-threatening disease that leads to the production and aggregation of misfolded toxic light chain proteins. These aggregates cause problems in the body’s circulation and are eventually deposited in the heart and kidney, leading to damage and organ failure. Patients may present with fatigue, weakness, numbness, among other symptoms – that can unfortunately lead to prolonged and/or incorrect diagnosis. Hear firsthand from a patient on her AL amyloidosis diagnosis experience here.

 

Q: Why are new treatment options needed for people diagnosed with AL amyloidosis?

A: Some common treatment choices for physicians include chemotherapies that have been repurposed from the treatment of multiple myeloma. They work by targeting the plasma clones that produce the misfolded light chain proteins, but do not alleviate the toxic, circulating aggregates nor the amyloid fibrils that have been deposited in the heart. Even on chemotherapy, patients still have issues with lasting effects such as morbidity and low quality of life.

 

Q: What’s in Prothena’s pipeline in AL amyloidosis?

A: Birtamimab* is a humanized monoclonal antibody being developed by Prothena that binds to the misfolded light chain proteins and not the normal, healthy light chains. It has also been shown to bind both types of light chains, kappa and lambda, as well as the circulating toxic aggregates and deposited amyloid fibrils in the heart. When birtamimab* binds to this amyloid, it signals to the immune system that it should be neutralized. The birtamimab* antibody is then recycled back into circulation so it can target more amyloid. You can read more about birtamimab* here.

 

Q: What prompted Prothena to initiate the AFFIRM-AL clinical trial in patients with Mayo Stage IV AL amyloidosis?

A: Prothena has been committed to the AL amyloidosis community for the past decade and continues to show our commitment via the confirmatory, global phase 3 AFFIRM-AL clinical trial. We recently published a paper in Blood on the VITAL clinical trial, which included patients in all Mayo stages with cardiac involvement. This trial ended early due to futility, but in a post hoc analysis of patients by different stages, our team found that patients with Mayo Stage IV experienced significant survival benefits, including increases in the six-minute walk test and overall quality of life. The FDA confirmed we could pursue the current confirmatory trial in this specific population.

 

Q: What is Mayo Stage IV AL amyloidosis and how are the stages different?

A: There are several staging systems used to describe AL amyloidosis patients. In the 2012 Mayo staging system, there are three biomarkers where the presence of each and the level of each determine the severity and prognosis. Mayo Stage IV AL amyloidosis describes those patients that have the highest levels of cardiac biomarkers and greatest difference in the amount of the two types of light chains.

 

Q: Why was it important to Prothena to continue to pursue the AL amyloidosis clinical program despite earlier hurdles?

A: We are committed to the AL amyloidosis patients, caregivers, patient organizations, and to the multidisciplinary physicians that care for this community. The AFFIRM-AL confirmatory trial is an example of that commitment. Our dedication to patients with AL amyloidosis motivates us to further investigate the significant clinical benefit seen in the Mayo Stage IV subset to hopefully deliver a different option.

 

* Birtamimab is an investigational therapy for the potential treatment of Mayo Stage IV AL amyloidosis. It has not been approved for use by any regulatory agency.