Anselamimab Shows Strong Survival Benefits for Certain AL Amyloidosis Patients in Phase III Study

People living with advanced light chain (AL) amyloidosis often face a very difficult journey.

The disease can damage vital organs such as the heart and kidneys, and treatment options that directly remove existing amyloid deposits have been limited. Now, new Phase III data suggest that an investigational therapy called anselamimab could offer meaningful benefits for a specific group of patients.

The results come from the global CARES Phase III clinical programme, which evaluated anselamimab alongside standard treatment for newly diagnosed patients with advanced AL amyloidosis.

While the study did not meet its primary endpoint in the overall patient population, the results revealed significant benefits in patients with kappa light chain amyloidosis.

Understanding AL amyloidosis

AL amyloidosis is a rare and progressive disease caused by abnormal plasma cells in the bone marrow.

These defective cells produce abnormal proteins known as light chains. Over time, these proteins misfold and form amyloid fibrils that accumulate in organs and tissues.

The heart and kidneys are often the most affected organs.

As these deposits build up, they can lead to:

• Progressive organ damage
• Heart failure
• Kidney dysfunction
• Reduced quality of life
• Premature death

Globally, around 74,000 people are estimated to be living with AL amyloidosis.

Approximately:

• 20% have kappa light chain amyloidosis
• 80% have lambda light chain amyloidosis

What makes anselamimab different?

Anselamimab is designed to target one of the biggest challenges in AL amyloidosis.

Most current treatments focus on stopping the production of abnormal light chains. However, they do not directly remove the amyloid deposits that have already accumulated in organs.

Anselamimab takes a different approach.

It is a monoclonal antibody designed to bind directly to amyloid fibrils and help the body clear these harmful deposits.

The goal is simple: remove existing amyloid buildup and potentially improve organ function.

Because of this unique mechanism, anselamimab is being developed as a potential first-in-class anti-fibril therapy.

What was the CARES Phase III programme?

The CARES programme is the largest prospective clinical study ever conducted in patients with cardiac AL amyloidosis.

The programme enrolled 406 patients across 19 countries.

Participants had advanced cardiac involvement and were classified as:

• Mayo stage IIIa disease
• Mayo stage IIIb disease

All patients received standard plasma cell dyscrasia treatment, which typically included cyclophosphamide, bortezomib and dexamethasone.

Around 80% of patients also received daratumumab as part of their treatment regimen.

Patients were randomly assigned to receive either:

• Anselamimab plus standard therapy
• Placebo plus standard therapy

The primary endpoint was missed

The main goal of the study was to evaluate a combination of:

• Time to all-cause mortality
• Frequency of cardiovascular hospitalisations

Across the entire study population, anselamimab did not achieve a statistically significant improvement compared with placebo.

As a result, the trial did not meet its primary endpoint.

However, the story did not end there.

Strong results emerge in kappa light chain patients

Researchers had planned in advance to analyze patients based on their light chain subtype.

This analysis revealed a striking finding.

Among patients with kappa light chain amyloidosis, anselamimab delivered meaningful improvements compared with placebo.

Improved survival

Patients receiving anselamimab experienced a 62% reduction in the risk of death from any cause.

This was one of the most important findings from the study and suggests that the treatment may have a significant impact on long-term outcomes for this subgroup.

Fewer cardiovascular hospitalisations

The treatment also reduced cardiovascular hospitalisations by 71%.

For patients living with advanced cardiac amyloidosis, avoiding repeated hospital visits can have a major impact on both quality of life and overall health.

Benefits seen across disease severity

The survival advantage was observed in both major disease stages studied.

Among patients with:

• Mayo stage IIIa disease, mortality risk was reduced by 75%
• Mayo stage IIIb disease, mortality risk was reduced by 48%

These findings suggest that the treatment's benefit may extend across different levels of disease severity.

What about patients with lambda amyloidosis?

The results were very different for patients with lambda light chain amyloidosis.

Researchers did not observe meaningful differences between anselamimab and placebo in terms of:

• Overall survival
• Cardiovascular hospitalisations

This distinction is important because most AL amyloidosis patients have the lambda subtype.

The findings suggest that anselamimab's clinical benefit may be primarily limited to patients with kappa disease.

Additional signs of clinical improvement

Researchers also looked at several secondary measures that provide insight into how patients feel and function in daily life.

At 50 weeks, patients with kappa amyloidosis who received anselamimab showed numerical improvements in:

Quality of life

Quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire.

Patients receiving anselamimab generally reported better outcomes compared with those receiving placebo.

Physical function

Physical capacity was evaluated using the Six-Minute Walk Test.

Patients treated with anselamimab were able to demonstrate better walking performance than those in the placebo group.

While these improvements did not reach formal statistical significance, the trends favored anselamimab.

Safety profile remains encouraging

Safety remains a critical consideration in patients with advanced cardiac disease.

According to the CARES programme results, anselamimab was generally well tolerated.

Researchers reported:

• An acceptable overall safety profile
• Similar rates of adverse events between treatment groups
• No unexpected safety concerns

Most side effects appeared consistent with the underlying disease itself and the standard therapies patients were already receiving.

Why these findings matter

The CARES programme may represent an important step forward in AL amyloidosis research.

For years, treatment strategies have focused primarily on reducing production of abnormal light chains.

Anselamimab introduces a different concept: actively targeting and clearing existing amyloid deposits from affected organs.

The results suggest that this strategy could translate into meaningful clinical benefits for patients with kappa light chain amyloidosis.

If future regulatory discussions and additional analyses support these findings, anselamimab could become the first therapy specifically designed to remove amyloid fibrils while improving survival outcomes in this patient population.

What happens next?

The results are being presented at the 2026 American Society of Clinical Oncology Annual Meeting and have also been published in the Journal of Clinical Oncology.

The developer, Alexion Pharmaceuticals, plans to continue discussions with regulatory authorities regarding the future development of anselamimab.

The therapy has already received:

• Fast Track Designation from the U.S. Food and Drug Administration
• Orphan Drug Designation in the United States
• Orphan Drug Designation in Europe
• Orphan Drug Designation in Japan

These designations highlight the significant unmet need that still exists in AL amyloidosis treatment.

Final takeaway

The CARES Phase III programme did not achieve its primary endpoint across all patients with AL amyloidosis. However, the study uncovered something potentially very important.

In patients with kappa light chain amyloidosis, anselamimab significantly improved survival and reduced cardiovascular hospitalisations while maintaining an acceptable safety profile.

For a disease where treatment options remain limited and organ damage can be devastating, these findings suggest that targeting existing amyloid deposits could become a new therapeutic strategy.

While more regulatory review and clinical discussions are still ahead, anselamimab has emerged as one of the most promising investigational therapies currently being studied for patients with kappa AL amyloidosis.