Heart disease breakthrough as ‘gene silencer’ drug shows promise

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’Gene silencers’ have shown promise in reducing heart attacks, strokes and deaths caused by a rare heart disease.

The drug Vutrisiran, sold under the brand name Amvuttra, works by binding to, and stifling, messenger RNA (mRNA) to reduce a disease-causing protein called transthyretin.

Researchers are hopeful the treatment – which is given as an injection – could become “the new standard of care” for patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

ATTR-CM happens when the faulty transthyretin proteins do not form correctly and build up in the heart’s main pumping chamber, making it more difficult to pump blood.

The condition can be hereditary or develop with age.

Professor Marianna Fontana, of University College London (UCL) and Royal Free Hospital, said: “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.

“We investigated whether a novel RNA interference (RNAi) therapeutic, vutrisiran, which targets transthyretin production, could improve clinical outcomes in patients with ATTR-CM and the results were very promising.”

The study, known as HELIOS-B, involved 655 patients from 87 sites across 26 countries.

More than three quarters (77.6%) had heart failure and 40% were 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 half were given a placebo.

Researchers found the risk of death and recurring “cardiovascular events” – such as heart attacks or strokes – were reduced by 28% overall and by 33% in patients only on vutrisiran.

Subgroup analysis showed risks were lowered by 20% in the 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 found that the quality of life of patients on vutrisiran improved compared to the placebo group.

Prof Fontana added: “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.

“Our findings indicate that vutrisiran has the potential to become the new standard of care.

“This trial is also important as it is the first to show the benefit of gene silencers in any type of cardiomyopathy.”

Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said the findings – presented at the ESC Congress in London – “unlocks” the potential benefits of so-called gene silencing.

“Transthyretin amyloidosis causes progressive heart failure, which can be devastating for patients and their families, and is difficult to treat,” he said.

“This study reveals the promising effects of a new kind of treatment, with vutrisiran significantly reducing the number of deaths, and improving the quality of life of those with this condition.

“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.”

Pushkal Garg, chief medical officer at vutrisiran manufacturer Alnylam, said: “While the results have not yet been reviewed by a regulatory authority, the data we have shared today suggest that vutrisiran has the potential to become a new standard of care treatment for ATTR-CM, a progressive and ultimately fatal disease with limited treatment options.”

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 the peripheral nerves throughout the body to malfunction.

The new research comes after a study by by UCL and Queen Mary University of London estimated one in 1,000 people could carry the genetic variant which puts them at risk of developing ATTR.

The figure, derived from analysis of 469,789 UK Biobank patients, is “higher than expected”, researchers said.