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Key Takeaways

  • A small clinical study showed that a new RNA-targeted medication lowered blood pressure for up to six months.
  • Zilebesarin is injected straight into the liver, targeting its effects there.
  • Current hypertension medications focus on hormones that cause high blood pressure; this one targets the RNA that creates the hormones.
  • The drug is years from market, but research is ongoing.

Treatment is available for the more than 122 million Americans living with high blood pressure, but many patients find it hard to adhere to a daily dosage schedule. A small study on a new medication published in the New England Journal of Medicine may have revealed a compound that would reduce the need for pharmaceutical treatment to once every six months.

The phase 1 study observed 107 patients—80 received an injection of an investigational drug called zilebesiran. This investigational RNA interference therapeutic agent inhibits the production of the protein that causes hypertension, or high blood pressure. The remainder of the participants received a placebo.

While very early in the research phase, zilebesiran had a promising effect: Those who received the drug had significantly lower systolic and diastolic blood pressure with few side effects.

The results are particularly noteworthy given the dosage schedule. After one injection of zilebesiran, a patient’s blood pressure levels were sustained for up to 24 weeks. This is encouraging to researchers, and the drug is going on to further trials.

How the Drug Works

According to study coauthor Akshay Desai, MD, MPH, Medical Director of the Cardiomyopathy and Heart Failure Program at Brigham and Women’s Hospital and Associate Professor at Harvard Medical School, zilebesiran is a new pharmaceutical that stops the liver from producing proteins that trigger high blood pressure before they start.

While high blood pressure has many contributing lifestyle factors, chemically, it is the product of the angiotensinogen (AGT) protein. According to Desai, several hormonal systems contribute to high blood pressure, and AGT is the precursor to most of them.

“If you can block the foundational step in that cascade, then you can limit production of those other hormones which may be important in driving elevations in blood pressure,” Desai told Verywell. “This is essentially a gene-targeted mechanism for suppressing one of the key hormonal systems involved in the pathogenesis of hypertension, or high blood pressure.”

Ian Del Conde, MD, cardiologist and director of vascular medicine at Miami Cardiac and Vascular Institute, part of Baptist Health South Florida, told Verywell that addressing the RNA effectively acts as prevention.

“Zilebesiran is novel because it inhibits the expression of the gene encoding angiotensin, which plays a key role in hypertension,” Del Conde said. “Other drugs commonly used to treat hypertension act by blocking the effect of angiotensin, but they do not prevent its synthesis.”

Longer Lasting Benefits

Current hypertension medications focus on blocking hormones already circulating in the bloodstream, such as ACE inhibitors or angiotensin receptor blockers (ARBs). Unfortunately, oral ACE inhibitors or ARBs can have significant side effects since they are taken orally. Desai says that the effects can be more precisely targeted with fewer side effects because zilebesiran is injected directly into the liver.

In addition to fewer side effects, a longer-lasting pharmaceutical action means that human error is less of an issue.

“Daily medication requires patients to take it for it to work. It requires constant administration of the drug,” Desai says.

A single injection also means that the drug’s effects are more even over time.

“When you take a drug once or twice a day, the drug has a peak effect, and then the nadir effect (low point),” Desai said. But with a biannual injection of zilebesiran, “you may get more consistent blood pressure reduction over the 24-hour cycle.”

Although that long action from an injection can be seen as a benefit, Desai said it could also be seen as a downfall. There may be times when patients and physicians want to be able to affect blood pressure daily. Further research is ongoing to explore how the effects could be manipulated with salt loading or other blood pressure manipulation tactics.

How It Could Be Used

While taking treatment further up the synthesis chain is encouraging, Desai emphasizes that zilebesiran is still in the early stages of study. There are currently two more extensive clinical trials, KARDIA-1 and KARDIA-2.

And while the results of the first phase are promising, Desai said that zilebesiran will likely still be only one weapon in an arsenal of pharmaceuticals aimed at combatting hypertension.

“We don’t expect that even if it were wildly successful, it would be the only agent that everybody would require,” Desai said. “It would be likely a foundational agent on which other agents would be layered.”

Part two of the study will examine how zilebesiran works with other hypertension medications, such as irbesartan, or other drugs that may have a complementary effect.

What This Means For You

Since zilebesiran is in the early stages of research, it won’t be commercially available for many years. But its early success shows promise for yet another RNA-focused medication that can stop symptoms before they start. Desai says he sees the phase one study as “proof of concept.” Del Conde agrees. The goal is to find safe, effective, and convenient treatment for hypertension.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics—2023 update: a report from the American Heart Association. Circulation. 147(8):e93-e621. doi:10.1161/CIR.0000000000001123

  2. Desai AS, Webb DJ, Taubel J, et al. Zilebesiran, an RNA interference therapeutic agent for hypertension. N Engl J Med. 2023;389(3):228-238. doi:10.1056/NEJMoa2208391

By Rachel Murphy

Rachel Murphy is a Kansas City, MO, journalist with more than 10 years of experience.



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