Phase 3 DISSOLVE Trials Prove SEL-212's Urate-Lowering Ability in Chronic Gout

The phase 3 DISSOLVE I and DISSOLVE II trials have met their primary endpoint of achieving serum urate-lowering among patients with chronic refractory gout, according to an announcement from Selecta Biosciences Inc and Sobi.¹

Announced by the companies on March 21, the trials examined use of SEL-212, which is a combination of Selecta’s ImmTOR immune tolerance platform and pegadricase, in adult patients with chronic refractory gout and concluded use of the agent elicited a response rate of 56% in patients in DISSOLVE I and 47% in patients in DISSOLVE II.¹

"Based on these data, I believe SEL-212 has the potential to provide an important new uricase-based treatment option for patients with chronic refractory gout. These patients suffer from chronic pain and endure debilitating functional impairment,” said principal investigator of the DISSOLVE Program Herbert S. B. Baraf, MD, clinical professor of Medicine at George Washington University School of Medicine and Health Sciences.¹ “The demonstrated profound lowering of the serum uric acid in the DISSOLVE program should meaningfully impact the quality of the lives of these severely afflicted patients. SEL-212’s favorable safety profile, coupled with the convenient once monthly treatment regimen, will be welcomed by patients with this challenging form of gout and the physicians who treat them."

Replicate trials, the randomized, double-blind, placebo-controlled, parallel arm DISSOLVE I and II make up the phase 3 DISSOLVE clinical program. Designed with the intent of examining the effects of once-monthly SEL-212, a novel, investigational serum urate-lowering combination therapy, in a patient population with refractory gout, DISSOLVE I was conducted in the US while DISSOLVE II was an international trial.

Both trials examined 2 different dose levels of SEL-212 and both had a primary endpoint of serum urate control during month 6. Secondary endpoints of interest for the trials included tender and swollen joint counts, tophus burden, patient-reported outcomes of activity limitation and quality of life and gout flare incidence. For the purpose of analysis, a treatment response was considered a reduction in serum urate level to less than 6 mg/dL for at least 80% of the time during month 6.^2,3

In DISSOLVE I, the observed response rates for the primary endpoint were 56% and 48% of patients randomized to receive SEL-212 at the high dose of 0.15 mg/kg (P <.0001) and the low dose of 0.1 mg/kg (P <.0001) of ImmTOR, respectively, compared to 4% among the placebo arm. In DISSOLVE II, the observed response rates for the primary endpoint were 47% and 41% of patients randomized to receive SEL-212 at high dose (P=.0002) and low dose (P=.0015) of ImmTOR, respectively, compared to 12% among the placebo arm.¹

Additional highlighted results from the release included the efficacy profile in older patients. Response rates among those aged 50 years and older receiving SEL-212 in DISSOLVE I were 65% and 47% among those receiving the high dose (P <.0001) and low dose (P <.0001), respectively, compared to 5% among the placebo group. In DISSOLVE II, response rates among this subgroup were 48% and 45% among those receiving SEL-212 at the high and low dose, respectively, compared to a 14% response rate among the placebo group. The release also called attention to a mean reduction of 69% in serum urate levels among those randomized to SEL-212 at 0.15 mg/kg in DISSOLVE I relative to placebo therapy.¹

In regard to safety, the companies’ release pointed out SEL-212 was well-tolerated across both doses of ImmTOR. Overall, treatment-related serious adverse events were observed in 6 patients, including 2 cases of anaphylaxis and 1 gout flare in both the high and low dose treatment groups.¹

In their release, the companies noted plans to present detailed results of the trials at an upcoming medical meeting and a regulatory submission in the US is anticipated in the first half of 2024.¹

“Altogether, the DISSOLVE program data instils confidence in SEL-212, and we look forward to further exploring its therapeutic potential as we drive forward development on a potential commercial path forward. We remain committed to bringing our therapies to the global patient community as quickly as possible,” said Anders Ullman, MD, PhD, Head of Research and Development and Medical Affairs and the Chief Medical Officer of Sobi.¹

References

1. Phase 3 dissolve program of SEL-212 in chronic refractory gout meets primary endpoint. Selecta Biosciences Inc. https://ir.selectabio.com/news-releases/news-release-details/phase-3-dissolve-program-sel-212-chronic-refractory-gout-meets. Published March 21, 2023. Accessed March 21, 2023.
2. A study of SEL-212 in patients with gout refractory to conventional therapy - full text view. A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04513366. Accessed March 21, 2023.
3. A study of SEL-212 in patients with gout refractory to conventional therapy II - full text view. A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04596540. Accessed March 21, 2023.