Background/Purpose: 

Pegylated uricases are therapies for treatment of severe chronic gout, particularly for rapid resolution of tophi. However, uricases are limited by induction of anti-drug antibodies that can compromise efficacy and safety. SEL-212 is a novel combination product consisting of pegadricase (also known as pegsiticase) co-administered with synthetic vaccine particles encapsulating rapamycin (SVP-R). We report initial Phase 2 data on the effect of the intensive lowering of sUA levels by SEL-212 on the dissolution of monosodium urate (MSU) crystals in symptomatic gout patients.

Dual-energy computed tomography (DECT) may be used to differentiate urate crys­tals from calcium by using specific attenuation characteristics, to diagnose gout. DECT uses a computer algorithm to produce color-coded images that render uric acid green, cortical bone blue, and trabecular bone purple. In tophaceous gout patients, DECT may be used for serial volumetric quantification of subclinical tophi to evaluate response to treatment.

Methods: 

Patients with symptomatic gout (≥1 tophus, gout flare within 6 months or gouty arthropathy) and elevated serum uric acid (sUA) ≥6 mg/dL were treated with fixed doses of pegadricase (0.2 mg/kg or 0.4 mg/kg) alone or in combination with SVP-Rapamycin (0.05 to 0.15 mg/kg).  SEL-212 was infused in 28-day cycles x3 doses followed by challenge with pegadricase alone on 28-day cycles x2 doses, or in 28-day cycles x5 combination doses of SVP-Rapamycin and pegadricase.

To investigate changes in uric acid deposits, DECT scans of hand/wrist, feet/ankles, and knees will be performed as an exploratory measure for at least 2 patients in study cohorts which included fixed doses of pegadricase (0.2 mg/kg or 0.4 mg/kg) in combination with SVP-Rapamycin (0.1 to 0.15 mg/kg), during the screening visit, treatment period 3, treatment period 5 or at early termination visit.  

DECT images were analyzed by Arthritis Research Canada (ARC) by two DECT Radiologists utilizing a Syngo Via DECT software package.

Results: 

As of 31 May 2018, an initial DECT scan was performed in 24 patients (143 dosed patients), with 10 patients undergoing a follow-up DECT scan.

The demographics for patients who received a follow-up DECT scan were 44 – 71 years old (mean 57.7 years), male 80%, Black or African American 70%, and Caucasian 30%.  Mean BMI at baseline was 31.8 kg/m², with 50% of patients being obese.  Mean duration of gout was 6.6 years.

The mean sUA at the screening visit was 8.3 mg/dl. Time between the initial and most recent/follow-up DECT scan ranged from 77 – 147 days (mean 103 days), with a mean change in total urate volume of -1.53 cm³ (range: 0.1 to -11.44 cm³). 

Figure 1: DECT Scan Images Showing Reduction of Urate Volume After Exposure to SEL-212

Conclusion: 

SEL-212 has a significant impact on the reduction of urate deposits in symptomatic gout patients with hyperuricemia as confirmed by DECT.