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SEL-212, an alternative to standard therapy that is administered once monthly, has proven to be particularly helpful for patients with severe gout, a historically underserved population.
In an interview with HCPLive Rheumatology, Herbert S B Baraf, MD, FACP, MACR, Clinical Professor of Medicine, George Washington University School of Medicine and Health Sciences and Principal Investigator of the DISSOLVE Program, discusses the phase 3 DISSOLVE program that evaluated SEL-212 combination therapy in adult patients with chronic refractory gout.
The program was comprised of 2 double-blind, placebo-controlled studies randomized patients to receive ImmTOR (0.1 mg/kg or 0.15 mg/kg), which hinders the formation of anti-drug antibodies, co-administered with pegadricase (0.2 mg/kg), or placebo. SEL-212 was designed to reduce serum urate (SU) levels in patients with chronic refractory gout, a more severe form of the condition.
What prompted your team to analyze the effects of SEL-212 in patients with chronic refractory gout?
Herbert S B Baraf, MD: I have a career-long interest in gout and have conducted clinical research on it. I was involved in the development of pegloticase, also known as KRYSTEXXA, and saw its transformative potential. However, many patients are sensitive to it and lose efficacy because they develop antibodies. This issue has been partially addressed with the use of methotrexate in conjunction with the drug. SEL-212 is a two component infusion treatment that begins with an infusion of a sirolimus-containing nanoparticle followed shortly by an infusion of pegadricase. Like Pegloticase, pegadricase is a uricase enzyme to which polyethylene glycol moieties are attached. While polyethylene glycol is meant to decrease immunogenicity and increase the half-life of these drugs, foreign proteins are inherently immunogenic. Thus, the value of these treatments is limited by their degree of immunogenicity. In the original phase 3 protocol with pegloticase, there was a 42% response rate, with many patients unable to tolerate the drug due to antibody formation and subsequent clearance of the drug from the system. Some patients also experienced infusion reactions. With the ImmTOR technology, however, pegadricase can be given more effectively, helping patients tolerate the drug and providing sustained benefits, as shown in this study.
Results indicated that SEL-212 was well tolerated, safe, showed significantly higher response rates, and a significant overall reduction in serum urate compared with the placebo. Were you surprised by these results?
HB: I was surprised at how low the incidence of infusion-related reactions was in this fairly large population of patients. There were only 7 true infusion reactions, 5 of which were anaphylactic, which was under 5%, whereas I would have expected the overall infusion reaction rate to be close to 20%. I was also surprised by the robustness of response in the over-50 population, with a 65% response rate in the US cohort. The addition of methotrexate to pegloticase therapy was approved by the FDA in the last year or so and showed a 70% response rate in one double-blind study, which is very similar to the response rates for SEL-212.
SEL-212 has the advantage of being administered once a month, compared to pegloticase, which is administered every 2 weeks, making it more convenient for patients. This type of therapy is particularly helpful for patients with severe gout, who have been underserved by the medical community. It can restore function and improve disfiguring tophaceous deposits on the hands and feet in just 3 to 6 months, whereas standard therapy takes 5 to 6 years. While both therapies are extremely effective, not all patients respond to either one, so having an alternative is great for patients. It is also great for doctors who can now feel more comfortable treating patients who need aggressive therapy. Having a second product in the pipeline for approval gives hope to those who need it.