A pair of Boston research centers are part of a global clinical trial studying if an investigational drug can help patients with a devastating disease live longer.

Dana-Farber Cancer Institute and Boston Medical Center are among the nation’s top medical centers taking part in the ongoing confirmatory Phase 3 AFFIRM-AL clinical trial, testing an investigational drug called birtamimab made by Prothena Biosciences, in patients diagnosed with an advanced stage (Mayo Stage IV) of a rare disease known as AL amyloidosis. Birtamimab is an investigational drug and is not approved by any regulatory authority.

AL amyloidosis occurs when a type of immune cell, called plasma cells, produce high levels of an abnormal protein called light chain that misfolds and clumps together to form aggregated amyloid which the body cannot break down. Clumped together, the amyloid can travel through blood vessels, damaging cells and depositing in the heart, kidneys, and other vital organs to cause disease. If left untreated, the deposits can lead to organ failure and death. 

Current AL amyloidosis treatments, including one which targets plasma cells that produce new misfolding light chain proteins, have no effect on the deposited amyloid causing damage in the vital organs. There remains a significant and urgent unmet need in advanced AL amyloidosis for therapies that go beyond the limitations of current treatments to help improve survival in these patients at highest risk for early death.

“Time is of the essence in AL amyloidosis, making early and accurate diagnosis critical for positive outcomes,” said Vaishali Sanchorawala, M.D., hematologist and director of the Amyloidosis Center at Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine. “Achieving a complete hematologic response is a main goal of treatment but doesn’t address amyloid already deposited in vital organs. Reducing light chain production and clearing amyloid deposition in vital organs are important thresholds for hopefully improving overall survival.” 

AL amyloidosis is a difficult disease to recognize and diagnose. Symptoms depend upon which organs are being affected, and many of the symptoms are similar to more common diseases and conditions, which explains why patients may see multiple doctors before receiving an accurate diagnosis. Research suggests that a diagnosis can lag approximately two years behind the initial onset of symptoms – all the while more organ deterioration is occurring. The heart is the most frequently involved organ, followed closely by the kidneys.

Due to the nature of the disease, the symptoms of AL amyloidosis tend to develop slowly over time. At the beginning, the symptoms can be minor, but as the misfolded light chain aggregates deposit over time as amyloids and cause organ damage in the body, the disease can reach a threshold where symptoms rapidly progress, which can become fatal. Such rapid progression explains why a patient might feel well early on, but quickly become quite ill.

“Early diagnosis, increased awareness, and newer treatment options on the horizon will hopefully improve health outcomes for this serious, life-threatening disease. From my perspective, the future is bright for patients with AL amyloidosis, as scientific advances are instilling hope for healthcare professionals and patients alike, especially those with the most advanced form of this disease.”

— Vaishali Sanchorawala, M.D.

New therapies are needed to address the damaging light chain fibrils and amyloid deposits in organs. Dana-Farber Cancer Institute and Boston Medical Center are participating in the global AFFIRM-AL clinical trial evaluating birtamimab – a different kind of investigational drug being explored for AL amyloidosis patients with significant cardiac involvement. Birtamimab is an investigational humanized anti-amyloid monoclonal antibody designed to specifically and selectively block misfolded light chains from forming into fibrils and to clear the amyloid that builds up and causes organ dysfunction and failure.

The trial is looking at the effect of birtamimab on survival, quality of life, and physical functioning in patients newly diagnosed with significant cardiac involvement. In AL amyloidosis, there are several staging classification systems. One classification system used to stage the prognosis of AL amyloidosis is the Mayo 2012 Staging system, a classification system that uses specific laboratory tests to determine the stage for newly diagnosed patients. This particular staging system classifies Mayo Stage IV as the most severe stage of disease. Worldwide, there are an estimated 60,000 to 120,000 people living with Mayo Stage IV AL amyloidosis. For patients in this advanced stage, there are very few treatment options, and none as of yet have been shown to reduce mortality. 

“The AFFIRM-AL clinical trial is evaluating if the investigational drug birtamimab, which has been shown in non-clinical studies to remove amyloid deposits, can improve survival in patients with advanced AL amyloidosis where early mortality remains high.”

— Vaishali Sanchorawala, M.D.

Enrollment for the AFFIRM-AL clinical trial is open. Patients may be eligible to participate in the AFFIRM-AL clinical trial if they are newly diagnosed with Mayo Stage IV AL amyloidosis and have not yet received any medical treatment for the condition. Study participants must be 18 years or over. Eligible patients who choose to participate in the clinical trial will receive the standard of care, study supplies or study-related tests and assessments, and either birtamimab or placebo at no cost. More information about eligibility for the AFFIRM-AL clinical trial can be found by visiting www.affirm-al.com.

Scientific research is vital to gain a deeper understanding of rare diseases such as AL amyloidosis and provides the greatest source of hope for advancing innovation to deliver therapies that can meaningfully improve the lives of patients, especially those with late-stage disease.