FDA approves Krystexxa  (pegloticase), after a year's delay



                                    Tophi treatment should improve





This page - the FDA approves Krystexxa (pegloticase) - was last reviewed, or updated, on 14 January 2013. 

This is the first of our two pages about the FDA approval for Krystexxa. Use the link at the bottom of this article to go to the second page, which discusses risks and side effects.

LATEST As of January 2013, Krystexxa has been approved for chronic tophi adult patients in the E.U. Read more on the second page 

N.B. Krystexxa™ is its brand name. Pegloticase is its generic name.

In the summer of 2009 it looked like Krystexxa would be approved by the FDA, the first medical authority it has been submitted to for marketing approval. An arthritis advisory committee of the FDA had earlier voted almost unanimously that the FDA should approve this new gout drug. But it didn't, citing problems with labeling, and safety information. And it required changes in manufacturing procedures. It did not say the drug did not work well enough, nor that it did not have an acceptable reward/risk profile.

Its developers, Savient Pharmaceuticals, worked out these problems, and after just over a year's delay, the good gout news is that FDA has now approved its use in the U.S. It will be infused into patients at a dosage of 8 mg every 2 weeks. The treatment will take around 2 hours per visit.

Krystexxa lowers uric acid by converting it to mainly allantoin, a substance which is much more soluble and more easily excreted by the kidneys than uric acid, which is not very soluble. Most animals get rid of uric acid by this method using uricase for the conversion, but we humans can't. We lost the ability to do this millennia ago, so most animals have 10 – 50 times less uric acid than we do. On the other hand, uric acid is a useful antioxidant.

So this is a new gout medicine, and it is one that works very differently to all but one of the other drugs for gout. It is specifically for treatment failure chronic gout patients and there are estimated to be 170,000 of this kind of gout sufferer in the U.S. It is delivered by intravenous infusion (IV). The drips out of bags or bottles, through needles into a vein that you have seen in films and on T.V. Or perhaps you've already undergone it.

Rasburicase for gout – in a small population

Pegloticase is somewhat similar to rasburicase, because both drugs convert uric acid to allantoin, but the new gout medicine Krystexxa does it in a way that's suitable for treatment failure chronic gout patients. Rasburicase is a very specialised (specialized) gout drug prescribed to a very small gout population. It has been available in many countries for a number of years but its use is mainly for patients suffering from tumor lysis syndrome which can occur after some cancer treatments, when there is a high risk, among others, of hyperuricemia (high uric acid) at very high levels, and therefore gout attacks, and kidney failure. 

Krystexxa's phase 3 studies

We'll now look at some salient results from the two phase three studies. There were three groups in each study. Those taking Krystexxa every two weeks, those taking it every four weeks and those on a dummy substance (a placebo).

It should be remembered that this drug was trialed on patients for whom other drugs for gout hadn’t worked. Their chronic gout was like this....a composite picture of both the groups taking Krystexxa was they had suffered gout on average for 17 years; had 10 acute gout flares in the previous 18 months, nearly half of them in over three joints, and ¾ had tophi. And most had serious medical conditions as well as chronic gout. These were often the very frequent maladies linked with gout – heart diseases, high blood pressure (hypertension), kidney disease, diabetes, dyslipidemia (excess blood fats eg.triglycerides and cholesterol), and many others.

Uric acid goes down fast 

There’s no doubt that Krystexxa is good at reducing uric acid levels in those that respond well to it. It seems to begin working on uric acid as soon as it enters the bloodstream. For example, in the trials, some patients who had uric acid levels above 10.0 mg/dL(0.594 mmol/L; 594 umol/L) - which is high - had levels below 1.0 mg/dL (0.059 mmol/L; 59.4 umol/L) within just hours. 

Nothing like this has ever been seen before in reducing uric acid by any of the drugs for gout.

And in the combined results of two phase 3 studies, those taking Krystexxa every two weeks began with an average plasma (blood) uric acid level of around 9.8 mg/dL, which is high by uric acid level standards – 7.0 mg/dL in men is upper normal and about 6.0 mg/dL in women. By month 3 (or more or less three months later) it had fallen to around 3.0 mg/dL on average among those who hadn't dropped out. 

Actually it fell to its low in the first week, and generally stayed around that low in both the groups who received 8.0 mg of pegloticase - either every 2 or every 4 weeks. By month 6 of treatment the uric acid levels were still about the same, so on average uric acid hadn’t risen again. Those taking Krystexxa every 4 weeks, who responded well, also did well but not quite as well - down from an average 9.9 mg/dL to 4.9 mg/dL in month 6.

Just under half did well 

On the other hand, in the phase 3 studies, under 50% of the every 2 weeks, and the every 4 weeks groups, actually responded in months 3 and 6 to the extent that their uric acid levels remained below 6.0 mg/dL, for 80% of the time. This is the crucial level at which gout crystals are thought to dissolve, and maybe tophi begins to shrink. 

Quite good against tophi 

It has also had some success against tophi, most likely more than any other gout drug. Beating tophi takes longer than reducing uric acid. You have to get uric acid down first, before tophi will start shrinking. In combined results from two studies 22% had resolved at least one tophi after 13 weeks, in the every 2 week group and 8% in the every 4 weeks group. After 25 weeks, 65% in the every 2 weeks group and 50% in the every 4 weeks group had shown complete or partial response to at least one tophus. 

But once again there wasn't universal success. 35% (2 weeks group) and 50% (4 weeks group) showed no improvement, or their tophus or tophi had even got worse, after 25 weeks, or if you prefer, almost 6 months. The Krystexxa dose will be every 2 weeks, so the 2 weeks' numbers matter most. 

But after the OLE extension trial, another, later study after the phase 3 trials had finished, a further 31% of previous non responders had cleared up at least one tophi. My guess is that most responders who go on longer will get better results.

And remember for your own case of gout, that this took longer for most patients than merely the time it took to reduce uric acid to the 6.0 mg/dL average level. 

Reduced gout attacks 

Against gout flares it was also quite successful.  For example in the every 2 weeks group 59% had no attacks in months 4 – 6, and 33% had attacks described as mild to moderate, almost certainly reduced in severity by treatment. But 7% still had severe attacks. In the every 4 weeks group results were not quite as good but still useful – 44% had no attacks in months 4 – 6, 47% had mild to moderate attacks and 9% still had severe ones.

The numbers in the first 3 months, and perhaps some of the numbers up to 6 months, would have been affected by the fact that a falling uric acid level causes flares, and it did in these studies despite the advance prevention medicine. Results from the OLE extension trial improved these scores – after 5 months, patients taking Krystexxa every 2 weeks no longer had gout flares.

There were also reductions in pain levels and in the number of swollen and tender joints.

To read all the statistics in detail go to the download links on our second FDA approval for Krystexxa page.

BOLD CAPS WARNING – IF YOU’RE CONSIDERING A KRYSTEXXA COURSE, ENSURE YOU READ CAREFULLY THE MEDICAL INFORMATION ON 

http://www.krystexxa.com 

Make sure you read the prescribing information and patient medication guide. The Krystexxa site says it's intended for U.S.audiences only.



Related pages you may enjoy

Read our second page about the FDA approves Krystexxa - the risks and side effects of the drug, it's EU approval for certain gout patients, and to read full statistics..... go to the free downloads on this second  page.

Read a third page about Krystexxa (pegloticase) here.

And read about Krystexxa for those with tophi here

Read about a new gout drug under development that may become the most successful at clearing up tophi.


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