A new clinical trial published in JAMA has confirmed that a twice-yearly injection of zilebesiran can lead to sustained reductions in blood pressure for patients whose hypertension isn’t adequately managed by standard treatments.
The findings suggest that RNA-based injection therapies could become a low-frequency, high-efficacy alternative to daily oral medications, especially for patients at risk of nonadherence.
The global study, known as KARDIA-2, evaluated the safety and efficacy of zilebesiran across 663 patients and found the treatment to be significantly more effective at lowering blood pressure compared to standard bp medications alone.
Key Study Highlights
- Zilebesiran is a subcutaneous RNA-interference therapy targeting angiotensinogen production in the liver.
- The injection is given once every six months, offering long-term blood pressure control.
- Patients who received zilebesiran experienced greater BP reductions compared to those on standard treatment alone.
- The therapy is well tolerated and could be especially beneficial for patients with poor adherence to daily medication regimens.
- Next steps include larger outcomes-based Phase III trials assessing zilebesiran’s ability to prevent heart attacks, strokes, and cardiovascular deaths.
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The Global Burden of Hypertension and Treatment Challenges
Hypertension affects approximately one in three adults in the UK and over 1.2 billion people worldwide.
Uncontrolled blood pressure significantly increases the risk of heart attacks, strokes, kidney failure, and premature death.
While several effective treatments exist, adherence remains a major challenge, particularly with multi-drug regimens requiring daily intake.
KARDIA-2 aimed to address this issue by testing a low-frequency injectable solution for long-term BP control.
Study Design: Zilebesiran vs. Standard Care
The KARDIA-2 trial included 663 patients with uncontrolled hypertension despite being on standard therapy.
Participants continued their existing blood pressure medications and were randomized to receive either zilebesiran injections or a placebo.
Zilebesiran is designed to silence the gene responsible for producing angiotensinogen, a liver-derived protein that contributes to blood vessel constriction.
By blocking this protein using RNA interference (RNAi) technology, zilebesiran helps relax blood vessels and lower vascular resistance.
Results: Meaningful and Sustained Blood Pressure Reduction
Patients who received zilebesiran experienced significant reductions in blood pressure sustained over six months.
Compared to placebo, the treatment group achieved greater declines in both systolic and diastolic BP measurements.
The subcutaneous injection was well tolerated, with no major safety concerns reported during the trial period.
According to the research team, this approach may provide a breakthrough alternative for people struggling to manage hypertension with daily medications.
Expert Commentary: Why This Therapy Matters
Dr. Manish Saxena, Clinical Co-Director at the William Harvey Clinical Research Centre and lead UK investigator of the study, emphasized the clinical relevance of the results.
“This study demonstrates the efficacy and safety of zilebesiran, when added to commonly used first-line BP drugs,” said Saxena. “The novelty of this treatment is its long duration; giving just one injection every six months could help millions of patients to better manage their condition.”
Dr. Saxena highlighted the global need for therapies that address the adherence gap in hypertension management.
What’s Next: Phase III Trials and Cardiovascular Outcomes
Following the promising results of KARDIA-2, researchers plan to launch KARDIA-3, another Phase II study targeting patients with established or high-risk cardiovascular disease.
The goal is to determine whether zilebesiran can serve not just as a BP treatment but as a comprehensive cardiovascular risk-reduction strategy.
Later in 2025, the sponsor, Alnylam Pharmaceuticals, will initiate a large-scale global outcomes study.
This trial will assess whether zilebesiran reduces major cardiovascular events, including strokes, heart attacks, and cardiovascular death.
The current study was co-led by Barts Health NHS Trust, which served as the top enrolling site in Europe for the KARDIA-2 trial.
