This page on gout tophi and pegloticase was last reviewed or updated on 13 January 2013.
Pegloticase, (its generic name), which was previously called PEG/Uricase, will be used as tophi treatment in chronic gout sufferers for whom other medications haven't worked. Its developers applied to the US FDA for approval in 2009. The application did not succeed, but the reasons for this were not really connected to the drug's efficacy or safety. It was approved by the U.S.FDA in mid September 2010.
In early January 2013 it was approved by the European Medicines Agency for the EU, where it is also called Krystexxa. Approval was given for adult patients in the E.U. with tophaceous gout. Krystexxa's developers think it can be launched in the EU by mid 2013.
It completed its phase 3 trials and went through an extension trial (OLE trial). The developers, Savient Pharmaceuticals, will to move for approval in other countries, beginning with member nations of the European Union.
Pegloticase is not a xanthine oxidase inhibitor, unlike febuxostat or allopurinol, and it does not encourage the kidneys to excrete uric acid as does probenecid. It works in a subtle way by converting uric acid into a substance called allantoin. Allantoin is more soluble than uric acid and better excreted in urine. Hence uric acid levels fall. Most mammals don't get gout because they can convert uric acid to allantoin, but we humans can't. It is taken as a series of intravenous infusions - in its trials, every two or four weeks, but as an approved drug, every two weeks.
The reason why Krystexxa (pegloticase) has shown considerable, but not complete, success against tophi in its trials is that it reduces uric acid (UA)by a significant amount. In some cases, UA levels went down to 1.0 mg/dL and most trial patients who completed the trials, kept their uric acids levels below the critical 6.0 mg/dL level for 80% of the time during months three and six.
And it has been found that the lower you can reduce uric acid, the more tophi you can clear up.
Savient has said in its reports, that complete clearing up of tophi has not been shown in any randomized (randomised) controlled trial for the other uric acid lowering medications.(However, they may be able to do it in the real world).
TRIAL RESULTS OF PEGLOTICASE ON TOPHI
What Savient have said so far is very encouraging. The company is particularly pleased with it effects on tophi.
In December 2007 Savient said:
"We believe that the most clinically important of the secondary efficacy outcomes assessed in these studies was the effect of pegloticase on gout tophi. The every two week dose arm (i.e. the group of patients taking pegloticase every two weeks) attained statistical significance in the pre-specified pooled analysis for the elimination of gout tophi (complete elimination of at least one tophus and no new tophi), whereas the every four week dose group did not attain statistical significance."
In combined results for phase 3 studies in the every two weeks' group (the period Krystexxa will be administered) 45% of 40 patients had a complete clear up, and another 20% a partial response. It took about four months to clear up a tophus but a few patients did it in three.
In May 2008 the company said:
"31% of the patients who were non-responders for the resolution of gout tophi at the end of Phase 3, showed a complete response in the OLE, (an extension trial that was popular continuation with many earlier particiants), with additional patients showing a partial response for tophus resolution."
There appears to be a similar pattern to febuxostat. The longer you take it, the more likely it is that you will clear tophi gout up.
In June 2008 the CEO of its developing company, in a regular presentation about pegloticase's progress to financial analysts, made upbeat statements about the medication. In his remarks about pegloticase and tophi, there was a definite delight in his voice when he described one case of how a multi-tophi sufferer, after 25 weeks of pegloticase treatment during the phase three trials, had cleared them up. And some of the tophi had been "weeping." i.e. exuding pus, which makes their disappearance even more welcome, necessary and encouraging.
Pegloticase is for a certain category of gout sufferer, treatment failure chronic gout sufferers i.e. if other drugs simply don't work, (Krystexxa) pegloticase may be prescribed. For most gout sufferers it won't be the first drug on offer.
However, for long-term tophi sufferers, for whom other medications haven't worked, there's definitely hope here.