Gene-based drugs show promise in lowering cholesterol levels, reveals new studies

New Delhi: Gene-based drugs could help lower cholesterol levels in patients with naturally high levels of the lipid in their blood, according to new studies published in the New England Journal of Medicine. Researchers of the two studies said that the drugs can be given to patients by injection four times a year. The studies analyse the performance of two gene-based drugs plozasiran and zodasiran in early stage (phase-2b) clinical trials in terms of safety and efficacy.

These drugs are RNA-based, meaning they are made using small pieces of ribonucleic acid, which is present in all living organisms.

Formed from DNA, or deoxyribonucleic acid, RNA converts information present in DNA into proteins involved in all bodily functions and processes. The RNA material present in the drugs binds with the RNA naturally present in the body and prevents it from making proteins known to play roles in regulating 'bad' cholesterol levels, the researchers explained.

While plozasiran helps limit the formation of the protein apolipoprotein C3, zodasiran reduces the production of the protein angiopoietin-like 3 (ANGPTL3), according to the authors.

Both the drugs, developed by US-based Arrowhead Pharmaceuticals, were found to significantly lower triglyceride levels in patients with mixed hyperlipidemia, a congenital disease in which an individual has naturally higher levels of cholesterol and fat in their body. These patients were already taking cholesterol-lowering drugs, known as statins.

High triglyceride levels increase the chances of high 'bad' cholesterol in the body.

Plozasiran was trialled in a total of 353 participants, who were divided into cohorts. Two doses of 10 milligrams (mg), 25 mg, or 50 mg of plozasiran were administered once every 12 weeks or once every 24 weeks, the researchers said.

At week 24, triglyceride levels were found to have lowered by almost 50 per cent in the patients given the 10-mg-quarterly dose, whereas the levels were cut down by 56 per cent in the patients administered the 25-mg-quarterly dose.

Further, in the patients given the 50-mg quarterly dose, triglyceride levels fell by 62.4 per cent, while in the patients given the 50-mg-half-yearly dose, these levels fell by 44.2 per cent, the researchers found.

Zodasiran was trialled in a total of 204 participants. Eligible patients were randomly assigned to receive subcutaneous injections of the drug (50, 100, or 200 mg) or placebo on day 1 and week 12 and were followed through week 36.

At week 24, the researchers observed "substantial" lowering in levels of ANGPTL3 protein, lower levels of which are linked with lower levels of cholesterol.

"Other differences in change from the baseline as compared with placebo included the following: for non-HDL cholesterol level, minus 29 percentage points with 50 mg, minus 29 percentage points with 100 mg, and minus 36 percentage points with 200 mg; and for LDL cholesterol level, minus 16 percentage points, minus 14 percentage points, and minus 20 percentage points, respectively," the authors wrote.

Zodasiran was also associated with lowered liver fat at week 24, with no adverse events related to liver function test changes reported so far, Arrowhead Pharmaceuticals said in a statement.

Further, plozasiran continued to show a favourable safety profile to date, according to the statement.

Arrowhead Pharmaceuticals develops RNA-based medicines for treating intractable diseases by silencing the genes that cause them, according to their website.