**Reducing Deaths from Rare Heart Disease: Potential of ‘Gene Silencer’ Drug**
Drugs known as “gene silencers” have shown promising results in reducing heart attacks, strokes, and deaths caused by a rare heart disease, according to a recent trial. The drug, vutrisiran, which is sold under the brand name Amvuttra, works by binding to and stifling messenger RNA (mRNA) to reduce a disease-causing protein called transthyretin. This breakthrough in treatment offers hope for patients suffering from transthyretin amyloid cardiomyopathy (ATTR-CM), a condition that can be hereditary or develop with age.
### The Mechanism of Action
ATTR-CM occurs when faulty transthyretin proteins do not form correctly and build up in the heart’s main pumping chamber, making it more difficult to pump blood effectively. Professor Marianna Fontana of University College London (UCL) and Royal Free Hospital explains, “ATTR is a progressive, fatal disease in which misfolded transthyretin protein accumulates as amyloid deposits in various parts of the body, often damaging the heart.” Vutrisiran, a novel RNA interference (RNAi) therapeutic, targets transthyretin production, potentially improving clinical outcomes for patients with ATTR-CM.
### The Clinical Trial: HELIOS-B
The study, known as HELIOS-B, involved 655 patients from 87 sites across 26 countries. More than three quarters (77.6%) of the patients had heart failure, with 40% already taking tafamidis, a medication to delay disease progression, which they continued with throughout the trial. For the study, half of the patients were given 25mg of vutrisiran once every three months for up to 36 months, while the other half were given a placebo.
### Promising Results
Researchers found that the risk of death and recurring heart attacks or strokes was reduced by 28% overall, and by 33% in patients only on vutrisiran. Subgroup analysis showed that risks were lowered by 20% in patients on both vutrisiran and tafamidis. After 42 months, the risk of death was lowered by 36% in patients overall and 35% in patients only on vutrisiran. The trial also revealed that the quality of life of patients on vutrisiran improved compared to the placebo group.
### Expert Opinion
Prof Fontana stated, “Vutrisiran was highly effective and well tolerated in this contemporary population representative of patients that we see in our clinics, with consistent benefits regardless of background tafamidis therapy.” The results of this trial indicate that vutrisiran has the potential to become the new standard of care for patients with ATTR-CM, potentially revolutionizing treatment options for this rare heart disease.
### Future Implications
Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, emphasized the significance of the findings presented at the ESC Congress in London. He noted that the study unlocks the potential benefits of gene silencing as a new treatment approach for transthyretin amyloidosis, offering hope for patients with this devastating condition. The study reveals the promising effects of vutrisiran in reducing deaths and improving quality of life, bringing us closer to a new treatment option for those living with the disease.
### Treatment Recommendation
The National Institute for Health and Care Excellence recommends vutrisiran as an option for treating hereditary transthyretin-related amyloidosis in adults with stage one or stage two polyneuropathy, which causes malfunction of the peripheral nerves throughout the body. This recommendation underscores the potential impact of vutrisiran in addressing the underlying cause of ATTR-CM and improving outcomes for patients with this rare heart disease.
### Genetic Variant Discovery
Recent research by UCL and Queen Mary University of London estimated that one in 1,000 people could carry the genetic variant that puts them at risk of developing ATTR. This figure, derived from analysis of 469,789 UK Biobank patients, is higher than expected, highlighting the importance of early detection and intervention for individuals at risk of developing this rare heart disease.
In conclusion, the development of vutrisiran as a gene silencer drug offers new hope for patients with transthyretin amyloid cardiomyopathy. The promising results of the HELIOS-B trial demonstrate the potential of vutrisiran to reduce deaths, improve quality of life, and become the new standard of care for patients with this rare heart disease. Continued research and exploration of gene silencing therapies may pave the way for innovative treatment options for individuals living with ATTR-CM.