Puricase, First New Drug Treatment Approach For Gout In 40 Years, Could Potentially Revolutionise Treatment For Some

Main Category: Gout
Also Included In: Primary Care / General Practice
Article Date: 17 Jul 2006 - 0:00 PDT

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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