Omapatrilat remains on file for regulatory approval as new trial broadly favours risk-benefit ratio
Indications for omapatrilat — a new antihypertensive agent being developed by Bristol-Myers Squibb — continue to be investigated while the company evaluates its options for the drug, following a new trial.
Omapatrilat inhibits both angiotensin converting enzyme and neutral endopeptidase
and has been shown to be an effective antihypertensive. In 2002, the
US Food and Drug Administration declined an application to license omapatrilat — because
of concerns over related angio-oedema — and called for further
trials.
The latest trial aimed to resemble clinical practice more closely than
previous studies and has revealed that its risk-benefit ratio “appears
favourable in appropriate patients”. However, the study shows that
black people and smokers might be more at risk of serious side effects
than others.
The 24-week OCTAVE study (omapatrilat cardiovascular treatment versus
enalapril), funded by BMS, involved 25,302 patients with untreated or
uncontrolled hypertension. Subjects were randomised to omapatrilat 10mg
or enalapril 5mg titrated over six weeks to 80mg for omapatrilat and
40mg for enalapril, if needed. At weeks eight and 16, other antihypertensives
could be added to achieve target blood pressure.
At week eight, omapatrilat reduced systolic blood pressure 3.6mmHg more
than enalapril and was associated with less use of adjunctive therapy
by week 24 (19 per cent versus 27 per cent). Subjects on omapatrilat
were more likely to reach their target blood pressure regardless of co-morbid
conditions or whether the drug was used as initial, replacement, or add-on
therapy. However, angio-oedema was more frequent with the newer agent
(2.17 per cent versus 0.68 per cent with enalapril).
The researchers comment that the burden of disease associated with inadequate
treatment of hypertension is substantial. Although airways compromise
resulting from angio-oedema occurred in 1.6 per 10,000 patients treated,
life-threatening cardiovascular events occurred at a rate of 100 to 300
per 10,000 patients per year, depending on underlying cardiovascular
risk. Thus omapatrilat might be of particular benefit in patients with
blood pressure that is difficult to control and at increased cardiovascular
risk.
In black patients and smokers special caution would need to be taken
because of the increased rates of angio-oedema in these groups (American
Journal of Hypertension 2004; 17:103). |
The
Pharmaceutical Journal