Licensed Programs

SHP622 – Licensed to Shire plc

In 2011, we granted an exclusive license to ViroPharma Inc. (now part of Shire plc) covering use of our drug candidate, “OX1” (renamed by Shire as SHP622), and certain of our licensed patents and patent applications related to OX1. Shire is developing SHP622 for the treatment of Friedreich’s Ataxia (“FA”). This drug candidate is a naturally occurring small molecular weight compound (indole-3-propionic acid) that prevents oxidative stress by a combination of hydroxyl radical scavenging activity and metal chelation.

Phase 1 studies in healthy adults were completed in 2010. The drug was found to be generally well tolerated, and the pharmacokinetics revealed that the drug was rapidly absorbed and distributed in the body after oral administration.

Recently, Shire completed a Phase 1b trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHP622 in 55 adults with FA. SHP622 was generally safe and well tolerated when administered as single and multiple ascending doses. There were no severe treatment emergent adverse events (“TEAEs”) or deaths reported in either the single or multiple dose groups, and the majority of TEAEs were of mild severity. Overall, there were no clinically meaningful differences between SHP622 and placebo or between the single and multiple dose groups. The mean terminal elimination half-life ranged between 7.36 and 10.33 hours across all dose groups. Inter-subject variability appeared to be low to moderate.

SHP622 Phase 1b Study in FA Patients – Completed by Shire in June 2015

Phase 1b Safety, Tolerability, PK/PD Study of SHP622 in Adults With FA
Trial Design Randomized, Double-blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Studies
Arm 1 Experimental: Single dose of SHP622 or placebo
  • Four groups of 8 subjects each will receive a single dose of SHP622 (150 mg, 450 mg, 900 mg, or 1200 mg) or placebo.
  • Total of 32 patients
Arm 2 Experimental: Multiple doses of SHP622 or placebo
  • Three groups of 8 subjects each will receive multiple doses of SHP622 (300 mg, 600 mg, or 900 mg total daily dose) or placebo. SHP622 or placebo will be administered every 8 hours for 7 days with a single morning dose on Day 8.
  • Total of 24 patients
Enrollment 55
Completion Last patient was enrolled in June 2015; Formal study report completed in April 2016
Primary Objective Evaluate the safety and tolerability of single and multiple oral doses of SHP622 in subjects with FA
Secondary Objective Characterize the pharmacokinetics of SHP622 by investigation of the plasma concentration-time profile following single and multiple oral doses
Exploratory Objective Investigate the pharmacodynamic effects of SHP622 on plasma 8-isoprostane and malondialdehyde and urinary 8-hydroxydeoxyguanosine concentrations following multiple oral doses
Results SHP622 was generally safe and well tolerated when administered as single and multiple PO doses. There were no severe treatment emergent adverse events (“TEAEs”) or deaths reported in either the single or multiple dose groups, and the majority of TEAEs were of mild severity.
Next Steps Shire is determining the optimal path forward for this drug candidate.