Drug treats rare heart disease by silencing gene

A Phase 3 clinical trial of the investigational drug vutrisiran has shown that it can reduce the risk of death and recurring cardiovascular events in people with a specific heart condition.

The results of the trial, which were presented at the European Society of Cardiology congress and simultaneously published in The New England Journal of Medicine, are promising for patients with transthyretin cardiac amyloidosis (ATTR), a condition for which there are currently few treatment options.

Lead author Professor Marianna Fontana of University College London (UCL) said, 'Our findings indicate that vutrisiran has the potential to become the new standard of care.'

People with ATTR possess a gene mutation that leads to the development of a faulty version of the transthyretin (TTR) protein. This mutation causes the protein to form clumps in the heart that mean it becomes stiff and less able to pump blood around the body. Without treatment, ATTR typically leads to death in four to six years.

Within the body, DNA is converted into messenger RNA (mRNA) that is then used to produce proteins. Tiny sections of a type of RNA known as small interfering RNA (siRNA) can bind to mRNA and block its conversion into a protein.

Vutrisiran is a form of siRNA that suppresses the expression of the TTR gene, meaning there is a reduction in the levels of the faulty TTR protein that causes ATTR. This process is known as RNA interference and drugs that work this way are often referred to as 'gene silencers'.

The recent trial, called the HELIOS-B trial, included 655 patients with ATTR who received injections of either vutrisiran or a placebo. The results showed that participants who received vutrisiran had a 28 percent lower risk of death and recurrent cardiovascular events compared with the participants who received the placebo.

The researchers also found that vutrisiran led to improvements in participants' physical functioning and their quality of life and symptoms compared with the placebo. The benefits of vutrisiran were consistent in patients who were also receiving another treatment for ATTR called tafamidis.

The results of the HELIOS-B trial build on the findings of a trial carried out over ten years ago that showed vutrisiran could reduce the levels of TTR protein in the blood of healthy participants by more than 80 percent (see BioNews 713).

The HELIOS-B trial represents a significant step forward in the development of further treatments for people with ATTR. Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, based at the UCL Institute of Cardiovascular Science said: 'This study unlocks the benefits of gene silencing as a potential way to treat cardiomyopathies, bringing us another step closer to a new treatment option for those living with the condition. We look forward to further studies to better understand the benefits of this drug in a wider, more diverse patient group.'