The Swiss pharmaceutical company Roche has now presented positive results from a phase II study with the RNA interference agent zilebesiran. This drug alone resulted in a 15 mmHg reduction in systolic blood pressure.
1.3 billion people worldwide suffer from high blood pressure. Hypertension is a major risk factor for heart attacks, heart failure, kidney damage and strokes. Despite generally effective medications from the active ingredient classes of ACE inhibitors, angiotensin II receptor blockers, diuretics, calcium antagonists and beta blockers, not all patients are provided with optimal care. Therefore, research continues into additional active principles for drugs against high blood pressure.
Results published
A new strategy would be RNA interference (RNAi). These are short artificial RNA sequences that specifically block the body’s production of a protein. The US biotech company Alnylam has developed the RNAi drug zilebesiran in collaboration with Roche. It blocks the production of the protein angiogensinogen in the liver. Angiogensinogen is the only precursor of the angiotensin peptides ACE-I and ACE-II, which are centrally responsible for controlling or increasing blood pressure.
The main results of a phase II clinical trial conducted with zilebesiran have now been published. The study included 394 adults with previously untreated mild to moderate hypertension or with stable high blood pressure previously controlled with other medications. In five groups, they received either 150 milligrams or 300 milligrams of the active ingredient every six months, 300 or 600 milligrams of zilebesiran every three months, or a placebo injection under the skin for a year.
Goal was achieved
The planned goal was achieved in the study: Compared to the dummy drug, there was a reduction in mean systolic blood pressure of more than 15 in both the patient group that received 300 milligrams as a subcutaneous injection and in the group of test subjects who received 600 milligrams mmHg. This was evident after both three months and six months. There was one death from sudden cardiac death in the zilebesiran group that was not related to treatment. Serious adverse events occurred in 3.6 percent of subjects who received the real drug, but in 6.7 percent of patients taking placebo. Here too, no connection with the study medications could be discovered.
If approved by the drug authorities after large-scale Phase III clinical trials, the new active principle could offer an alternative, especially in cases of otherwise uncontrollable hypertension, despite a combination of the previously available and otherwise quite effective medications. In addition, conventional hypertension medicines have to be taken daily, which often only about half of patients can do in the long term.
Just a few weeks ago, Roche invested $310 million (equivalent to 289 million euros) in the Alnylam project. Around ten million people worldwide are expected to die as a result of hypertension every year. Optimal would be a blood pressure of less than 120 mmHg systolic (upper value/pumping phase of the heart) and less than 80 mmHg diastolic (lower value/resting phase of the heart). 120 to 129 mmHg and 80 to 84 mmHg are considered normal. 130 to 139 and/or 85 to 89 mmHg are considered “high normal.” First degree hypertension is 140 to 159 mmHg and/or 85 to 89 mmHg. 160 to 179 mmHg and/or 100 to 109 mmHg mean second-degree hypertension and more than 180 mmHg and/or more than 110 mm (diastolic) mean third-degree hypertension.
