Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In this randomized controlled trial, the antibody NI006 for the treatment of transthyretin amyloid cardiomyopathy (ATTR) showed no associated drug-related serious adverse events.

2. The pharmacokinetic profile of NI006 was similar to an IgG antibody with no antidrug antibodies detected.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

ATTR can cause progressive and fatal amyloidosis that may result from variants in the gene that encodes transthyretin or manifest due to a late-onset sporadic disease. Currently, there are no effective solutions for ATTR cardiomyopathy, with heart transplants serving as the only solution for restoration of cardiac function. There is an oral TTR stabilizer called tafamidis that can increase survival and reduce hospitalization, but unfortunately, this medicine does not prevent disease progression. Recently, NI006 has been developed and shown to deplete ATTR by inducing antibody-mediated phagocytosis of ATTR fibrils and removing ATTR deposits from tissues. However, there is a gap in knowledge as to understanding whether there is a treatment that can deplete ATTR from the heart and reverse the subsequent cardiac dysfunction. Overall, this study found that NI006 is safe and should be further studied for the treatment of patients with ATTR cardiomyopathy. This study was limited by a small sample size which can limit generalizability to other populations like young and female demographics. Nevertheless, these study’s findings are significant, as they demonstrate that NI006 has an acceptable safety profile and warrants further investigation.

Relevant Reading: Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy

In-Depth [randomized controlled trial]:

This phase one, double-blind, placebo-controlled, multicenter, randomized clinical trial was conducted at six specialized amyloidosis centers in four European countries. Patients who had a confirmed diagnosis of ATTR cardiomyopathy; a left ventricular wall thickness of at least 14 mm; a left ventricular ejection fraction of at least 40%; a New York Heart Association class of I, II, or III; an estimated glomerular filtration rate of more than 30 ml per minute per 1.73 m2; and an N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of 600 to 6000 pg per milliliter were eligible for the study. Patients who had received treatments with other ATTR-specific drugs (other than tafamidis) were excluded from the trial. The primary outcome measured was the safety and side-effect profile of NI006. Outcomes in the primary analysis were assessed via data aggregation to the same nominal grouping and absolute or relative change from the baseline. Based on the primary analysis, there were no significant drug-related serious adverse events and no antidrug antibodies were detected. Additionally, a cardiac tracer uptake study showed reduced cardiac amyloid load over a period of 12 months with reduced NT-proBNP levels. In summary, this study demonstrates that the NI006 human antibody appears to be safe and associated with no apparent drug-related serious adverse events, thus warranting further investigation into its efficacy as a treatment for ATTR cardiomyopathy.

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