BioWorld International Correspondent
LONDON Protherics plc announced positive results from a Phase IIa trial of its angiotensin vaccine for the treatment of hypertension, showing that all 17 patients developed antibodies against angiotensin and that there was a subsequent effect on aldosterone, another hormone influencing blood pressure.
Protherics CEO Andrew Heath told BioWorld International, “These results are part of a chain of evidence for what we believe is now the quite well-documented effect of this vaccine on hormonal control of blood pressure.”
The 17 patients were treated with the vaccine over a six-week period. Antibody levels peaked three weeks after the last dose. There was an antibody half-life of more than two months, supporting Protherics’ aim of developing a long-term treatment involving primary immunization followed by booster injections once or twice a year.
“These results show us two very important things,” Heath said. “The half-life of the antibodies means you can have spaced-out injections, and the very clear effect on aldosterone levels is a key proof of concept.”
As well as causing vasoconstriction, angiotensin prompts the secretion of aldosterone, the most potent hormone regulating the body’s electrolyte balance, which works by increasing the reabsorption of sodium and the excretion of potassium in the kidneys. Reabsorption of sodium is accompanied by reabsorption of water, raising blood pressure.
At the next stage in development, Protherics, based in Macclesfield, intends to optimize the formulation to maximize antibody titers. “The half-life of the antibodies is acceptable as it stands, but we believe we can get a longer duration of action and therefore extend the time between injections,” Heath said.
Although there are a number of drugs that control hypertension by blocking the effects of angiotensin, they must be taken daily, and since high blood pressure requires long-term control, compliance can be an issue.
One of the investigators, M.J. Brown, of the Clinical Pharmacology Unit of Addenbrookes Hospital in Cambridge, said, “Development of a treatment that avoids the need for daily drug therapy is an appealing prospect. This study is an important step in that direction, by demonstrating that long-lived immunity can be generated in patients with high blood pressure.”
Once the vaccine is optimized, Protherics plans to conduct a large-scale trial involving 360 patients with high blood pressure, commencing in late 2003.
In the meantime, the company is weighing its commercialization options. “We have had lots of approaches and there is a lot of interest,” Heath said. “When to partner is the subject of a lot of internal discussion at the moment.”