New Safety and Tolerability Data Available on CAEL-101 for AL Amyloidosis

Currently, the European Hematology Association (EHA) Virtual Congress 2021 is going on from June 9 through 17, 2021. During the Congress, hematologists and other stakeholders will discuss clinical research and new advances within this field. According to a news release, biotechnology company Caelum Biosciences (“Caelum”) and biopharmaceutical company Alexion Pharmaceuticals, Inc. (“Alexion”) presented two e-poster presentations during the Congress. The posters centered around Phase 2 safety and tolerability data on CAEL-101, in conjunction with current standard-of-care treatments, for patients with primary (AL) amyloidosis.


There are six main forms of amyloidosis, a condition in which abnormal proteins (amyloids) collect in organs, form deposits, and cause a host of health issues. In each case, the amyloids stiffen the organs and reduce organ function. The forms of amyloidosis include organ-specific amyloidosis; senile systemic (SSA/wild-type) amyloidosis; dialysis-related amyloidosis (DRA); familial (ATTR or non-ATTR); primary (AL); and secondary (AA), which is caused by another condition.

Despite its rare status, AL amyloidosis is the most common form of amyloidosis. In this condition, plasma cells within the bone marrow create too many light chains, or pieces of antibodies. When these misfiled and bind together, they form amyloids. These amyloids then settle in the heart, kidneys, nerves, skin or soft tissue, stomach, and large intestines. In AL amyloidosis, the heart and kidneys are often the most affected. Overall survival typically depends on how much the heart is impacted. However, the 1-year mortality rate currently sits around 47%, much of which is caused by cardiac complications.

Symptoms vary, based on which organs are affected. However, symptoms may include:

  • Shortness of breath, even with minimal exercise or activity
  • A feeling of fullness, even when not eating a lot
  • Abnormal heart rate
  • Nausea and vomiting
  • Diarrhea or constipation
  • Muscle or nerve pain, weakness, or tingling
  • Peripheral and autonomic neuropathy
  • Macroglossia (a swollen and enlarged tongue)
  • Unintended weight loss
  • Appetite loss
  • Nephrotic syndrome
    • Note: Typically, nephrotic syndrome manifests as proteinuria (excess protein in the urine) and edema (swelling) in the lower legs.
  • Kidney failure

Learn more about amyloidosis.


According to Caelum, CAEL-101 is:

a fibril-reactive monoclonal antibody (mAb) that is currently in Phase 3 clinical development for the treatment of patients with amyloid light chain (“AL”) amyloidosis.

Monoclonal antibodies (mABs) are laboratory-created proteins which help enhance the body’s immune response. According to Caelum’s President and CEO, current standard-of-care treatment for AL amyloidosis doesn’t address where amyloids have already formed in the organs. Rather, current treatments attempt to prevent new amyloid formation. But without treating existing amyloid deposits, organ damage worsens. Thus, CAEL-101 is designed to bind to misfolded proteins and reduce (or totally get rid of) existing amyloid deposits within organs and tissues. As a result, Caelum hopes that CAEL-101 can boost overall organ function.

Within a previous Phase 1a/1b clinical trial, 27 patients enrolled. These patients, who had relapsed and refractory (R/R) amyloidosis, were treatment-averse. In short, they had not responded well to previous care. However, after receiving CAEL-101, these patients saw overall improved organ function and a better quality of life (QOL).

CAEL-101 has also received Orphan Drug status in both Europe and the United States.

Poster Presentations

Data for the poster presentations was sourced from a Phase 2 clinical trial evaluating the safety, efficacy, and tolerability of CAEL-101 in conjunction with standard therapies. Additionally, researchers wanted to understand the ideal / recommended CAEL-101 dose to be used in further clinical trials. In the first part of the trial, patients received either 500, 750, or 1000mg/min conjunction CyBorD. Next, in the latter half of the trial, patients received 1000 mg/m2 CAEL-101 in conjunction with CyBorD and daratumumab. Ultimately, researchers determined that the 1000mg dose is the dose that will be used in Phase 3 clinical trials.

In the first poster presentation (#EP1017), researchers explained the safety and tolerability of CAEL-101 when used with CyBorD and daratumumab. The data showed that:

  • Altogether, this trial met its primary endpoints.
  • Within the first 4 weeks (1 month) of treatment, this therapy combination was both safe and relatively well-tolerated.
  • Adding daratumumab to the other two treatments did not affect the pharmacokinetics of CAEL-101.
  • Although the treatment was relatively well-tolerated, some side effects did occur. These included nausea, insomnia, and constipation.

Within the second poster presentation (#EP1018), researchers presented longer-term data sourced from the same clinical trial. In this case, the data showed that:

  • 13 patients enrolled. When receiving CAEL-101 and CyBorD, the treatment was relatively well-tolerated and safe for up to 49 weeks. During this period, most patients received 20+ CAEL-101 infusions.
  • CAEL-101 reduced biomarkers relating to cardiac disease and improved cardiac function overall in 8 patients. Additionally, 7 patients saw improved renal function and a 30% reduction in proteinuria.
  • Some side effects did occur. These included nausea, anemia (low red blood cell count), rashes, fatigue, and diarrhea.

Currently, researchers are enrolling patients to take part in two Phase 3 clinical trials. Altogether, 370 patients will enroll. Within these trials, researchers will continue developing their understanding of CAEL-101 in relation to other therapies.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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