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Sobi and Selecta Biosciences announce topline data of SEL 212 from the phase II COMPARE study supporting the potential for important clinical improvement in patients with chronic refractory gout.
Swedish Orphan Biovitrum AB (publ) (Sobi)and Selecta Biosciences, Inc. announced topline data for the phase II COMPARE study comparing the efficacy of SEL 212, a combination of Selecta's tolerogenic ImmTOR immune tolerance platform and a therapeutic uricase enzyme (pegadricase), to pegloticase Kyrstexxa), the currently approved uricase in the US , for the treatment of chronic refractory gout
. Per FDA guidance on Statistical Considerations for Clinical Trials during the COVID-19 Public Health Emergency, the statistical analysis plan was modified and submitted to FDA prior to database lock to address the potential impact of the COVID-19 pandemic on the statistical analysis of the study endpoints. This was necessary due to increased protocol deviations in the intention-to-treat (ITT) population observed during the ongoing COVID-19 pandemic. Data are therefore presented per protocol (PP) and ITT.
Topline results from the phase II COMPARE study are as follows : SEL 212 showed a numerically higher response rate on the primary endpoint during months 3 and 6 combined, but did not meet the primary endpoint of statistical superiority: SUA < 6 mg/dL for at least 80% of the time during months 3 and 6 combined: 59% SEL 212 versus 46% pegloticase, PP, p=0.056, 53% SEL 212 versus 46% pegloticase, ITT, p=0.181.Statistically significant higher response rate of SEL 212 during month 3: SUA < 6 mg/dL for at least 80% of the time during month 3: PP: 70% SEL 212 versus 51% pegloticase, p=0.019, ITT: 70% SEL 212 versus 54% pegloticase, p=0.017. Numerically higher response rate of SEL 212 during month 6: SUA < 6 mg/dL for at least 80% of the time during month 6: PP: 61% SEL-212 versus 47% pegloticase, p=0.053, ITT: 54% SEL 212 versus 47% pegloticase, p=0.179. Statistically significant greater overall reduction in mean SUA levels in SEL 212 versus pegloticase: Serum uric acid levels were reduced by an average of 6.68 mg/dL (computed by subtracting baseline SUA from mean SUA during the treatment period) for patients treated with SEL 212 versus 4.51 mg/dL for patients treated with pegloticase, p=0.003, during months 3 and 6 combined, PP; ITT: 6.79 mg/dL SEL 212 versus 4.85 mg/dL pegloticase, p=0.003. In patients with tophi at baseline, substantially higher responder rates for SEL 212 compared to pegloticase on the primary endpoint, and statistically significant reduction in mean SUA: Approximately 41% of patients in the phase II COMPARE study had visible tophi at baseline. A greater differential on the primary endpoint between SEL 212 versus pegloticase on patients with tophi was observed: PP: 58% SEL 212 versus 39% pegloticase; ITT: 57% SEL 212 versus 41% pegloticase. In these patients, the mean SUA levels were reduced by an average of 7.42 mg/dL for patients treated with SEL 212 versus 4.64 mg/dL for patients treated with pegloticase, p=0.016, during months 3 and 6 combined, PP; ITT: 7.32 mg/dL for SEL-212 versus 4.89 mg/dL for pegloticase, p=0.019.
Adverse events : SEL 212 and pegloticase showed favorable safety results and were well-tolerated: There were no deaths during the study. There were no notable differences in serious Treatment Emergent Adverse Events (TEAEs), treatment-related serious TEAEs, or infusion reactions between the two groups. A full analysis of safety signals, including gout flare incidence and severity, awaits evaluation of the full data set and will be reported together with the full efficacy analysis at a later medical meeting.
"There is a clear need for a next-generation treatment for chronic refractory gout, and the phase II COMPARE study demonstrated that SEL 212 led to a statistically significant reduction of serum uric acid levels versus standard of care in patients suffering from this painful, debilitating disease," said Robert T. Keenan, MD, MBA, MPH, board certified rheumatologist at Duke University School of Medicine and Principal Investigator of the COMPARE study. "I believe that SEL 212 could meaningfully impact the lives of patients and provide a much-needed alternative in the treatment paradigm for patients with chronic refractory gout."
Phase III trials planned: SEL 212 has been licensed to Sobi, with Sobi undertaking development, regulatory and commercial activities in all markets outside of China. Sobi and Selecta recently announced the initiation of two double-blinded, placebo-controlled phase III clinical studies (DISSOLVE I and DISSOLVE II) of SEL 212 for the treatment of chronic refractory gout. Topline data from the DISSOLVE programme is expected in the second half of 2022, and a Biologics License Application (BLA) filing is expected in the first quarter of 2023.
About the phase II COMPARE study : The phase II COMPARE study evaluated 170 patients with chronic refractory gout, with 83 receiving an infusion of SEL 212 once monthly for six months and 87 receiving an infusion of pegloticase twice monthly for six months. The primary endpoint measure was a comparison of the percentage of patients on SEL 212 versus pegloticase who achieved and maintained a reduction of serum uric acid (SUA) < 6 mg/dL for at least 80% of the time during months three and six combined. Key secondary endpoint measures included a comparison of the percentage of patients on SEL 212 versus pegloticase who achieved and maintained a reduction of serum uric acid (SUA) < 6 mg/dL for at least 80% of the time during month 3 and during month 6, separately, and reduction of mean SUA assessed at the three- and six-month time points. The PP population is defined as patients who were administered any amount of study medication and have completed at least 65% of the study dosing visits unless early termination from the study occurred after study drug withdrawal due to meeting stopping rules or due to an adverse event, or due to investigator discretion and who have no major protocol deviations affecting the primary efficacy assessments.
Condition: Gout
Type: drug