Puricase, First New Drug Treatment Approach For Gout In 40
Years, Could Potentially Revolutionise Treatment For Some
Article Date: 17 Jul 2006 - 0:00am (PST)
The first new class of drug to emerge in 40 years for treating
chronic gout has the potential to radically alter the outlook for
thousands of patients unable to benefit from currently available
therapies, says the drug's developer Savient Pharmaceuticals Inc.
who presented Phase II data at this year's annual meeting of the
European rheumatology community, EULAR.
Puricase (PEG-Uricase), a drug currently in Phase III clinical
trials has been shown in smaller trials to rapidly eliminate body
stores of excess uric acid (urate). Uric acid can lead to the
formation of crystals which are deposited in joint tissues where
they accumulate as tophi causing pain and inflammation. Often these
clump together to form disfiguring nodules. Gout has been described
as the most painful of all rheumatological conditions.
Savient Pharmaceuticals Inc, the small New Jersey-based company
developing the treatment says Puricase is a polyethylene-glycolated
recombinant version of the porcine enzyme, uricase. All mammals
except humans and primates produce the uricase enzyme which breaks
down uric acid leaving very low levels in the blood circulation with
no untoward effects. Uricase converts uric acid to the more
water-soluble metabolite allantoin that can be readily excreted.
The drug is administered by two-hour intravenous infusions every two
or four weeks and would probably be indicated initially for patients
with hyperuricaemia - excess blood levels of uric acid resulting in
severe tophaceous gout, resistant to or intolerant of conventional
therapy.
In the US around 3 to 5 million people suffer from gout and similar
numbers are affected in Europe. A tendency to develop the condition
is genetically determined but beer-drinking and consumption of
purine-rich, high protein foods are implicated to a small extent in
its development. Gout typically develops in men in their 40s or 50s
or less frequently in women after menopause. Treatment is based
either on inhibiting production of uric acid or increasing its
excretion. In addition, tissue inflammation can be treated with
colchicine or non-steroidal anti-inflammatory drugs (NSAIDs).
Some 2 million people in the US are treated with allopurinol tablets
- a drug that decreases the production of urate by inhibiting
another enzyme, xanthine oxidase. Up to 5 per cent of patients are
unable to tolerate allopurinol, however, because of adverse
reactions of which the most serious is a life-threatening
sensitivity reaction. In others, the drug can be ineffective.
Approximately a quarter to one third of all gout sufferers - around
half a million people in the US -develop tophi and gout flares
despite conventional therapy, said Savient's Chief Medical Officer
Zeb Horowitz.
Puricase has been shown in Phase II trials to successfully and
rapidly reduce plasma urate levels and gouty tophi. President and
CEO Christopher Clement commented: “Puricase is increasingly being
recognised among the rheumatological community as a potential
breakthrough treatment for this orphan gout patient population.”
Anecdotal reports testify to patients on Puricase treatment finding
themselves able to wear normal shoes again or use their fingers
properly, he noted.
Savient presented several posters at EULAR. One showed photographic
and radiographic evidence of the dramatic effects that Puricase can
achieve in individuals who have failed other treatments. Phase II
data show 8mg of PEG-uricase every two weeks achieved rapid
reductions in plasma urate to below target levels which were
maintained 92 per cent of the study duration. Pre-treatment levels
of 9.1mg/dl were reduced to a mean plasma urate level of 1.4mg/dl
over 12 weeks. A level of 6mg/dl is required to avoid flares.
Dr Herbert Baraf, a US rheumatologist and Puricase trialist from
Wheaton, Maryland, US, said conventional treatment, if effective,
reduces uric acid levels very slowly taking up to five years to
obtain complete resolution of painful tophi. Puricase however is
able to radically reduce uric acid crystal stores within three to 12
months.
“Many physicians and patients believe older therapies are sub
optimal and want better treatments,” commented Dr Horowitz. Early
intervention with Puricase as an alternative to conventional therapy
could potentially prevent the accumulation of uric acid crystals
that form tophi and keep patients from experiencing flares, he
suggested. However, this would have to be the topic of further
investigations. Puricase would need to be administered over six to
12 months only to eradicate body stores of uric acid. Because uric
acid stores take decades to build up to the level where they cause
symptoms, no further treatment might be needed. Most gout therapies
however need to be taken regularly for life.
Savient has world rights to Puricase, which was originally developed
by researchers at Duke University in North Carolina, and will market
it in the US itself. It is currently seeking a partnership with a
European company to develop Puricase for the European gout market.
By Olwen Glynn Owen
glynnowen@macline.co.uk
http://www.savientpharma.com