This page about uricase for gout, Uricase PEG-20 for gout, and Pegsiticase/SEL, was last reviewed or updated on 30 June 2017.
SUMMARY A new technology could give uricase a new lease of life and the world of gout treatment a big boost – the first non-immunogenic uricase. One that doesn't generate unwanted immune system responses.
Uricase, or urate oxidase, is an enzyme that metabolises uric acid. The name peg uricase, (or uricase peg), indicates it’s a pegylated version of uricase. Pegylation makes uricase less immunogenic. i.e it reduces uricase’s ability to generate unwanted immune system responses. We humans lost uricase function aeons (eons) ago, but most animals still have it. So uricase based drugs work in a way that humans have lost but “giving us our uricase back” is not simple.
In the name Uricase Peg-20, peg refers to pegylation
but why 20 ? This refers to the type of uricase pegylation used in the drug’s
formulation. It was considered this version is better for the patient’s immune
system reactions. The number loosely describes its pegylation’s ability to
Moreover with Uricase Peg-20, the origin of the uricase is different to other biologics.(see below). It can come from pigs, baboons, or a yeast.
Krystexxa and Rasburicase for gout
So Uricase PEG-20, is a related biologic drug for gout to Pegloticase (brand name: Krystexxa), and Rasburicase.(Elitek or Fasturtec).These are both also forms of uricase. Krystexxa is a biologic drug for difficult cases of gout. Rasburicase is a restricted-use anti uric acid drug used in cases of tumor lysis syndrome (TLS). TLS patients are at risk of developing high levels of uric acid.
The biologics are taken by intravenous injection over a few hours and may lower serum (blood) uric acid way down to levels below 3 mg/dL; in one trial pegloticase got it below 1mg/dL in some trialists, and they started at over 10.
As with Krystexxa and Rasburicase, Uricase PEG-20, which has been given the generic name of pegsiticase, is also intended for difficult and stubborn gout cases, not relatively new patients, because it’s good at reducing uric acid.
How do they lower uric acid? They convert
uric acid to allantoin which is easier to excrete from the body than uric acid.
Other gout meds do not work like this - they either restrict uric acid production or impove its excretion.
In the scientific world of gout, Uricase PEG-20 has been around in the background for a long time. There were even uricase tests on chickens in the 1940’s and on humans in the 1950’s. The first study of the pegylated Uricase form was in 1981. Uricase Peg-20 even went through Phase 1 clinical tests in the U.S.
But it was not brought to authority approval and the gout patient market, including during the years up to late 2010 when pegloticase was developed into the branded drug Krystexxa, and eventually approved in the U.S.
Uricase Peg-20 springs back to life as Pegsiticase/SEL-212
A few years ago a Chinese based company, 3SBio, bought it but we heard nothing more. Until mid 2014 that is, when it was announced that Selecta Biosciences Inc. of Massachusetts, U.S.A. had joined forces with 3SBio to develop Pegsiticase. And in a very novel way.
There is a very big idea here. The developing companies join Selecta’s SVP (synthetic vaccine particle technology), to 3SBio’s pegsiticase (Uricase Peg-20). The resulting compound is called SEL-212. The jargon to describe it is “immune tolerance application.”
What does that mean?
The problem with biologics, despite their pegylation, is their adverse reactions and side effects. SVP modifies the immune system’s response to the arrival of gout’s MSU crystals and inhibits harmful responses to biologic treatment. More about their adverse reactions on this page.
This is just what a gout biologic needs, since most patients treated with them develop unwanted reactions. In Krystexxa’s trials, a significant number of trialists – about 25% - even withdrew because of them. At the same time, pegsiticase is good at lowering uric acid in the manner explained.
You can see what a golden prize these two companies are aiming for – a very effective gout drug that lowers serum (blood) uric acid fast (in a matter of hours), and with a big reduction (down to nearly zero) and a treatment that doesn’t cause adverse reactions. If it works successfully, this will be something the other gout biologics – Krystexxa and Rasburicase - can't touch.
With SEL-212 the developers hope they can dramatically improve treatment for serious and stubborn gout cases, including tophi cases.
This one just might become the
most effective gout drug of all. It will need to demonstrate that it can
lower uric acid reliably, that is in a very high percent of patients, and of
course deliver a big reduction in immune reactions. The commencement of a phase 1 study for SEL-212 was announced in June 2015. In mid June 2017 Selecta Biosciences reported on its very positive Phase 2 trial, and announced they plan to begin in Phase 3 trials in 2018. These are the last before possible regulatory approval.
Selecta’s SVP treatment in gout is just one of other medical conditions where its immune tolerance proposition applies.
And further out in time, scientists have reconstructed another uricase from the time when it was at its height – during the dinosaur period - and this version might lead to a drug in the farther future.
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