Novel vaccine reduces BP by targeting angiotensin II
Targeting angiotensin II with a virus-derived vaccine — CYT006-AngQb — has been shown to reduce hypertension in a study published last week in The
Lancet (2008;371:821). However, the authors of an accompanying editorial (ibid, p788) raise concerns about the safety of circulating angiotensin II antibodies.
In the phase IIa study, 72 patients were randomised to receive either
100µg or 300µg of the experimental vaccine or placebo at
weeks 0, 4 and 12. Ambulatory blood pressure was measured for a 24-hour
period both before treatment and at 14 weeks.
Patients given 300µg of CYT006-AngQb experienced reductions in
ambulatory daytime blood pressure (significant for systolic [P=0.015]
but not for diastolic measurements), compared with those on placebo.
The 300µg dose reduced the early morning surge in blood pressure
for both systolic and diastolic measurements, compared with placebo (P<0.0001
and P=0.0035, respectively).
“The drop in blood pressure was especially pronounced in the early
morning when the renin-angiotensin-aldosterone system [RAAS] is most
active and
when most cardiovascular events occur,” the study authors write.
“This
effect was not anticipated at the beginning of the study. By contrast,
small molecule inhibitors of the [RAAS], while lowering blood pressure
over 24 hours, do not affect the surge in early-morning blood pressure.”
Influenza-like symptoms occurred in three patients receiving the 100µg
dose, in seven receiving 300µg and in none in the placebo group,
and these effects were mild and transient. Such effects are thought to
originate from the activation of the innate immune system that occurs
after immunisation, the authors say.
They also suggest that optimising the immunisation regimen with shorter
dosing intervals and a higher dose could lead to higher antibody titres
and a more robust antihypertensive effect. “Later stage clinical
trials will be needed to show efficacy and safety in a broader hypertensive
population,” they add.
The authors of the editorial, Ola Samuelsson and Hans Herlitz from Sahlgrenska
University Hospital, Sweden, believe that vaccination against high blood
pressure might solve many of the problems around non-compliance but they
spell out a number of concerns over the safety of the strategy.
They say that the long half-life of the antibodies against angiotensin
II — some 17 weeks — “raises the question of whether
it will be safe to inhibit the actions of circulating angiotensin II
for several months without the ability to quickly reverse inhibition,
which is easily done for drugs by withdrawal of treatment”.
They acknowledge the study authors’ finding that the blood-pressure
lowering effect was greatest during the early morning when the RAAS is
most stimulated but point out that situations can occur when a patient
would need a fully activated RAAS.
“Another important safety issue is whether repeated stimulation
of the immune system by booster doses of an endogenous peptide linked
to a virus-like
particle can cause autoimmune disease,” they add. |
The
Pharmaceutical Journal
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