Selecta Biosciences, a clinical-stage biopharmaceutical company focused on unlocking the full potential of biologic therapies by avoiding unwanted immune responses, today announced data from its ongoing Phase 2 trial of SEL-212 (SVP-Rapamycin in combination with the uricase enzyme pegsiticase), which is being developed for patients with chronic severe gout.
Key observations and findings based upon the clinical data generated through June 12, 2017 from the 60 patients currently enrolled in this open-label, dose ranging Phase 2 trial include:
- Mitigated anti-drug antibodies (ADAs) after repeat monthly administrations of SEL-212 – The prevention of ADAs in a dose-dependent manner resulted in durable control of serum uric acid (sUA) levels (defined as sUA <6 mg/dl). The clinical data demonstrate a correlation between the prevention of ADAs and the maintenance of pegsiticase activity and serum uric acid control.
- Demonstrated induction of immune tolerance – A majority of patients in the minimum effective dose group maintained sUA control following three monthly injections of SEL-212 and two monthly “challenge” injections of pegsiticase alone. Maintenance of sUA in the challenge portion of the trial provides evidence at this stage that the use of SVP-Rapamycin is enabling immune tolerance, meaning a prevention of ADAs to pegsiticase, which is typically immunogenic when administered alone.
- Reduced rate of gout flares with SEL-212 – In the control cohorts receiving pegsiticase alone, within the first month of treatment, 50% of patients reported experiencing a gout flare, which is a sudden and severe attack of pain, inflammation and tenderness of the joints. By comparison, only 15% of patients receiving SEL-212 reported a gout flare in the first month of treatment, with reports declining further in subsequent months. These data also appear to be in contrast with the increased incidence of flares reported in clinical trials involving other urate lowering therapies.
- Identified minimum effective dose of SEL-212 – A key objective of the Phase 2 trial was to determine a minimum effective monthly dose of the two components of SEL-212 (i.e. pegsiticase and SVP-Rapamycin) through an ascending dose matrix design. A majority of the initial patients dosed with 0.4 mg/kg of pegsiticase in combination with 0.08 mg/kg of SVP-Rapamycin maintained sUA control beyond five treatments. As a result, the company has determined this to be a minimum monthly effective dose of SEL-212. Additional patients are now being added to this cohort, and higher dose levels of SVP-Rapamycin are being tested to further determine the dose regimens that may be taken forward into Phase 3.
- SEL-212 generally well tolerated – Consistent with the expected reduction in immunogenicity of pegsiticase when SVP-Rapamycin doses increase, SEL-212 has been generally well tolerated at clinically active doses. There have been a total of eight serious adverse events (SAEs) reported in the trial through June 12, 2017. Seven were infusion reactions, four of which occurred in the cohorts receiving pegsiticase alone or the lowest dose of SVP-Rapamycin and two of which were due to dosing errors. One additional SAE, cholecystitis, was determined to not be related to the study drug. All of the SAEs were successfully treated and resolved without further issues.
“The implications of these trial data are profound for both SEL-212 and for the development of Selecta’s immune tolerance platform,” said Werner Cautreels, Ph.D., CEO and Chairman of Selecta. “First and foremost, the clinical data demonstrate SEL-212’s potential to address substantial unmet needs for patients with chronic severe gout, a debilitating disease that has been associated with both increased morbidity and mortality. We believe that a reduction of serum uric acid levels to near zero during treatment, a reduction in the incidence of flares and the convenience of safe monthly dosing with SEL-212 would prove to be a compelling treatment option. Leveraging these data, we are beginning to prepare for a Phase 3 program that we plan to initiate in 2018 following further dialogue with the U.S. Food and Drug Administration. Importantly, we also believe that our technology has shown for the first time in a clinical setting the potential to induce tolerance to a highly immunogenic biologic, which helps to inform the continued development of our other proprietary novel biologic programs.”