The new med voclosporin
could bring relief to plaque psoriasis sufferers
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A Canadian-developed drug that's
billed as a better, safer immunosuppressant for a host
of purposes has proven "reasonable efficacy" in a phase
III trial for plaque psoriasis. The calcineurin inhibitor
voclosporin, also known as ISA247, brought substantial
relief to just under half of the patients taking the
highest dose in the trial, with adverse effects much
milder than would be expected from its nearest cousin,
cyclosporine.
The double-blinded study, published
in The Lancet April 19, showed a remarkably consistent
relationship between dose and response. That predictable
dose-response curve, the drug's advocates say, should
help clinicians titrate doses to achieve symptom control
with the minimum of side effects.
Besides a placebo, three doses
were tried in the twice-daily oral regimen: 107 patients
received 0.2mg/kg of body weight; 113 patients received
0.3mg/kg; 116 patients received 0.4mg/kg; and 115 received
a placebo. All of the subjects were aged between 18
and 65, and had plaque psoriasis covering at least 10%
of their skin. The patients were followed up for 24
weeks.
The primary endpoint was a 75%
reduction in the psoriasis area and severity index,
the so-called PASI 75 score, after 12 weeks' treatment.
The proportion of patients who attained this mark was
4% in the placebo group, 16% in the 0.2 mg/kg group,
25% in the 0.3 mg/kg group, and 47% in the 0.4 mg/kg
group.
MILD
EFFECTS
Adverse events also rose predictably with dosage. Mild
to moderate glomerular filtration rate reductions were
noted in seven patients in the 0.4mg/kg group, one patient
in the 0.3mg/kg group and no patients in the other groups.
The overall number of side effects, even at the highest
dose, was not significantly greater than placebo, the
authors found, leading them to conclude that voclosporin
has "an improved safety profile."
Like cyclosporine, the drug it
aims to supplant, voclosporin has multiple potential
uses. The company that makes it, Edmonton-based Isotechnika,
says its principal goal is to prevent organ rejection
in kidney transplants. But it's likely that the first
approval for voclosporin won't be for this or for psoriasis,
but for the autoimmune eye disease uveitis. It's just
been put on the FDA fast track for approval for that
indication.
As for psoriasis, voclosporin has
cleared its first major hurdle with this study, but
some experts question if the bar was set high enough.
In a commentary accompanying the Lancet study,
Dr Luigi Naldi of the Ospedali Riuniti di Bergamo, Italy,
suggests that it's premature to claim a better safety
profile than cyclosporine when no trial has yet tested
the two head-to-head.
Dr Naldi also questions if 24 weeks'
followup is really enough to prove tolerability and
safety. "The risk of chronic nephrotoxicity induced
by calcineurin inhibitors increases with treatment duration
and cannot be reliably predicted with short-term data,"
he argues.
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