Contributions
Abstract: P1637
Type: LB Poster
Abstract Category: Late Breaking News
Background: CHS-131 is a novel, first-in-class, highly-selective PPARγ agonist. CHS-131 crosses the blood-brain barrier and has potent anti-inflammatory effects in the central nervous system without evidence of immunosuppression. CHS-131 has been studied in over 600 subjects in multiple indications and has been shown to improve clinical and neuropathological outcomes in animal models of experimental autoimmune encephalomyelitis. This study was designed to evaluate safety and efficacy of CHS-131 in treatment-naïve subjects with relapsing remitting multiple sclerosis (RRMS).
Methods: This randomized, double-blind, parallel-group, 2-part study randomised subjects to oral CHS-131 at 3 mg or 1 mg or Placebo in a 1:1:1 ratio at 21 sites in Russia. Subjects (age 18-50 years) had RRMS for ≤3 years, ≥1 gadolinium-positive lesion within 12 months of enrollment, and an Expanded Disability Status Score of 0-6 at screening. In Part 1, the primary endpoint was the number of new gadolinium contrast-enhancing (CE) T1-weighted lesions seen on monthly magnetic resonance imaging (MRI) over 6 months. All MRIs were read in a blinded fashion at a U.S. imaging centre. The study is ongoing; part 2 is an open label, 6-month, safety extension study, in which all subjects transition to 1 mg CHS-131 daily, to evaluate clinical response, CE lesions on MRI, and safety.
Results: This study enrolled 227 subjects with RRMS (mean age 31 years; 65% were female; BMI of 23.7), and 96.5% completed Part 1 (6 months). The mean number of new CE lesions over 6 months was 4.2 for 3 mg CHS-131 (n=70), 7.6 for 1 mg CHS-131 (n=70) and 7.8 for placebo (n=69). The response was dose-dependent, and the incidence of new CE lesions with 3 mg CHS-131 was significantly lower (46%) than with placebo (p=0.003), and the incidence with 1 mg CHS-131 was 3% lower than with placebo (p=ns).
Adverse events (AE) were reported in 32.9%, 26.3%, and 36.0% of subjects in the 3 mg CHS-131, 1 mg CHS-131, and placebo groups, respectively, and 10.5%, 3.9%, and 6.7% of subjects had AEs judged by the investigator to be related to treatment. No new safety signals were detected for CHS-131. There was no evidence of the immunosuppression or common toxicities observed with PPARγ full agonists.
Conclusions: This study demonstrated a statistically-significant decrease in the incidence of new CE lesions with 3 mg CHS-131 as compared with placebo over 6 months. CHS-131 was generally well-tolerated. Further study is warranted.
Disclosure: David Weinstein is an employee for InteKrin Therapeutics, Inc.; and is a consultant for and owns stock in Coherus BioSciences. Alexey Boyko is a consultant/advisor to InteKrin Therapeutics, Inc., and received speaking and consulting fees from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi and Novartis. Lisa Pugliese is on the Board of Zao InteKrin; and is an employee for and owns stock in Coherus BioSciences. Hong Tang is an employee for and owns stock in Coherus BioSciences. Robert Zivadinov received speaking and consulting fees from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health and Novartis and financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, InteKrin Therapeutics, Inc., Coherus BioSciences, and IMS Health. Barbara Finck is an employee for and owns stock in Coherus BioSciences.
This study was supported by a grant from the Ministry of Industry and Trade of the Russian Federation and sponsored by Coherus BioSciences and Zao InteKrin.
Abstract: P1637
Type: LB Poster
Abstract Category: Late Breaking News
Background: CHS-131 is a novel, first-in-class, highly-selective PPARγ agonist. CHS-131 crosses the blood-brain barrier and has potent anti-inflammatory effects in the central nervous system without evidence of immunosuppression. CHS-131 has been studied in over 600 subjects in multiple indications and has been shown to improve clinical and neuropathological outcomes in animal models of experimental autoimmune encephalomyelitis. This study was designed to evaluate safety and efficacy of CHS-131 in treatment-naïve subjects with relapsing remitting multiple sclerosis (RRMS).
Methods: This randomized, double-blind, parallel-group, 2-part study randomised subjects to oral CHS-131 at 3 mg or 1 mg or Placebo in a 1:1:1 ratio at 21 sites in Russia. Subjects (age 18-50 years) had RRMS for ≤3 years, ≥1 gadolinium-positive lesion within 12 months of enrollment, and an Expanded Disability Status Score of 0-6 at screening. In Part 1, the primary endpoint was the number of new gadolinium contrast-enhancing (CE) T1-weighted lesions seen on monthly magnetic resonance imaging (MRI) over 6 months. All MRIs were read in a blinded fashion at a U.S. imaging centre. The study is ongoing; part 2 is an open label, 6-month, safety extension study, in which all subjects transition to 1 mg CHS-131 daily, to evaluate clinical response, CE lesions on MRI, and safety.
Results: This study enrolled 227 subjects with RRMS (mean age 31 years; 65% were female; BMI of 23.7), and 96.5% completed Part 1 (6 months). The mean number of new CE lesions over 6 months was 4.2 for 3 mg CHS-131 (n=70), 7.6 for 1 mg CHS-131 (n=70) and 7.8 for placebo (n=69). The response was dose-dependent, and the incidence of new CE lesions with 3 mg CHS-131 was significantly lower (46%) than with placebo (p=0.003), and the incidence with 1 mg CHS-131 was 3% lower than with placebo (p=ns).
Adverse events (AE) were reported in 32.9%, 26.3%, and 36.0% of subjects in the 3 mg CHS-131, 1 mg CHS-131, and placebo groups, respectively, and 10.5%, 3.9%, and 6.7% of subjects had AEs judged by the investigator to be related to treatment. No new safety signals were detected for CHS-131. There was no evidence of the immunosuppression or common toxicities observed with PPARγ full agonists.
Conclusions: This study demonstrated a statistically-significant decrease in the incidence of new CE lesions with 3 mg CHS-131 as compared with placebo over 6 months. CHS-131 was generally well-tolerated. Further study is warranted.
Disclosure: David Weinstein is an employee for InteKrin Therapeutics, Inc.; and is a consultant for and owns stock in Coherus BioSciences. Alexey Boyko is a consultant/advisor to InteKrin Therapeutics, Inc., and received speaking and consulting fees from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi and Novartis. Lisa Pugliese is on the Board of Zao InteKrin; and is an employee for and owns stock in Coherus BioSciences. Hong Tang is an employee for and owns stock in Coherus BioSciences. Robert Zivadinov received speaking and consulting fees from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health and Novartis and financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, InteKrin Therapeutics, Inc., Coherus BioSciences, and IMS Health. Barbara Finck is an employee for and owns stock in Coherus BioSciences.
This study was supported by a grant from the Ministry of Industry and Trade of the Russian Federation and sponsored by Coherus BioSciences and Zao InteKrin.