Results from a Phase 2 study show combination of OCA 5-10mg and bezafibrate 400mg induced the greatest percent change from baseline in ALP at Month 6
OCA and bezafibrate combination therapy has acceptable metabolic profile
Results featured in podium presentation today at DDW 2024
MORRISTOWN, N.J., May 18, 2024 – Intercept Pharmaceuticals, Inc., a biopharmaceutical company and wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, is presenting new data from a planned six-month analysis of its ongoing Phase 2 study 747-213 evaluating a fixed-dose combination of obeticholic acid (OCA) and bezafibrate in patients with primary biliary cholangitis (PBC) at Digestive Disease Week® (DDW) 2024 in Washington, D.C. Results from the study show that six-month administration of OCA and bezafibrate has the potential to normalize alkaline phosphatase (ALP), a serum biomarker of PBC-related liver damage that has been correlated with improved transplant-free and decompensation-free survival.
“I am encouraged by the findings from this six-month analysis of the fixed-dose combination of OCA and bezafibrate,” said Alan Bonder, MD, Medical Director of Liver Transplant, BIDMC, and Associate Professor of Medicine, Harvard Medical School. “As a clinician, normalizing ALP is a key component of pharmacological therapy in PBC, and the impact of this combination on ALP, coupled with its ability to normalize total and LDL cholesterol, gives me confidence in this investigational therapy.”
Patients with PBC in study 747-213 were randomized 1:1:1:1 to receive 12 weeks of once-daily oral therapy in addition to ongoing ursodeoxycholic acid (UDCA) treatment (if any) in one of four treatment arms:
- bezafibrate 200 mg immediate release (B200 IR) (n=19)
- bezafibrate 400 mg sustained release (B400 SR) (n=19)
- bezafibrate 200 mg IR + OCA 5 mg titrated to 10 mg at week 4 (OCA5-10/B200 IR) (n=19)
- bezafibrate 400 mg SR + OCA 5 mg titrated to 10 mg at week 4 (OCA5-10/B400 SR) (n=18)
Following the 12-week double-blind treatment period, OCA-bezafibrate dosage could be optimized in the long-term safety extension.
The objectives of this study were to evaluate change in ALP from baseline to Month 6, as well as changes in lipid panel over the same time period.
Six-Month Results on ALP Reduction
- OCA/B400 SR induced the greatest percent change from baseline of ALP, resulting in a -65.3% reduction (p<0.05 vs. B400 SR)
- B400 resulted in a -49.0% change from baseline
- OCA/B200 IR induced a -42.4% reduction from baseline
- B200 IR induced a -39.3% change from baseline
Six-Month Results on Metabolic Outcomes
Mean total cholesterol was reduced to less than 200 mg/dl in the OCA/B400 SR arm along with 19% mean reduction in LDL cholesterol. HDL levels remained within normal range.
Total Cholesterol
- Only the OCA/B400 SR arm resulted in normalization of total mean cholesterol levels at Month 6 to less than 200 mg/dL
- OCA/B400 SR induced a -19.6% reduction from baseline (p=0.004 vs. B400 SR, which induced a -6.8% reduction from baseline)
- OCA/B200 IR resulted in a -14.5% reduction from baseline (p<0.05 vs. B200 IR, which induced a -5.9% reduction from baseline)
LDL Cholesterol
- OCA/B400 SR induced a -18.7% change from baseline
- OCA/B200 IR resulted in a -9.6% reduction from baseline
- B400 SR and B200 IR induced a -11.1% and -9.5% reduction from baseline, respectively
HDL Cholesterol
OCA/B400 SR and OCA/B200 IR both induced reductions in HDL cholesterol; however, levels remained within a normal range as defined by the U.S. National Library of Medicine.
- OCA/B400 SR induced a -17.9% reduction from baseline (p<0.05 vs. B400 SR, which induced a 7.5% increase from baseline)
- OCA/B200 IR resulted in a -14.9% reduction from baseline (p<0.05 vs. B200 IR, which induced a 5.9% increase from baseline)
“The results from this analysis provide important insights on the potential benefits of OCA-bezafibrate combination therapy in PBC,” said Sangeeta Sawhney, Senior Vice President and Head of U.S. Research & Development. “We have conducted multiple studies demonstrating the value of OCA – namely, transplant-free survival – and we are eager to continue innovating on behalf of people living with PBC by studying OCA’s apparent synergy with bezafibrate to further improve clinical outcomes. We look forward to presenting these data in further depth at DDW 2024.”
The company is continuing its two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468), which are exploring a range of therapeutic doses and formulations for the combination of OCA and bezafibrate.
