Intercept Unveils New Data on OCA-Bezafibrate Therapy's Impact on ALP and Metabolic Outcomes After Six Months at Digestive Disease Week® 2024

Intercept Pharmaceuticals, Inc., a subsidiary of Alfasigma S.p.A., has released promising data from a six-month analysis of its ongoing Phase 2 study 747-213. This study evaluates the combination therapy of obeticholic acid (OCA) and bezafibrate for patients with primary biliary cholangitis (PBC). Presented at Digestive Disease Week® (DDW) 2024 in Washington, D.C., the findings indicate that this combination therapy could significantly reduce alkaline phosphatase (ALP) levels, a key biomarker for liver damage in PBC patients, potentially enhancing transplant-free and decompensation-free survival rates.

Dr. Alan Bonder, Medical Director of Liver Transplant at BIDMC and Associate Professor at Harvard Medical School, expressed optimism over these results. He highlighted the importance of ALP normalization in PBC treatment and noted that the combination also positively impacts total and LDL cholesterol levels, bolstering confidence in its potential efficacy.

In the study, PBC patients were randomly assigned to one of four treatment arms in addition to ongoing ursodeoxycholic acid (UDCA) treatment where applicable. The groups received the following treatments over 12 weeks of once-daily oral therapy:

- Bezafibrate 200 mg immediate release (B200 IR)
- Bezafibrate 400 mg sustained release (B400 SR)
- Bezafibrate 200 mg IR combined with OCA 5 mg, titrated to 10 mg at week 4 (OCA5-10/B200 IR)
- Bezafibrate 400 mg SR combined with OCA 5 mg, titrated to 10 mg at week 4 (OCA5-10/B400 SR)

Upon completion of the 12-week double-blind period, the OCA-bezafibrate dosage could be adjusted for long-term safety.

The primary objective was to assess the change in ALP levels from baseline to Month 6. Secondary objectives included evaluating changes in lipid profiles over the same period.

Six-Month Results on ALP Reduction
- OCA/B400 SR showed the most significant reduction in ALP levels by -65.3%.
- B400 SR resulted in a -49.0% change.
- OCA/B200 IR yielded a -42.4% reduction.
- B200 IR showed a -39.3% change.

Six-Month Results on Metabolic Outcomes
- The OCA/B400 SR arm reduced mean total cholesterol to less than 200 mg/dL and decreased LDL cholesterol by 19%, while HDL levels remained normal.
- Only the OCA/B400 SR group normalized total mean cholesterol levels at Month 6, showing a -19.6% reduction.
- Changes in LDL cholesterol included:
- OCA/B400 SR: -18.7%
- OCA/B200 IR: -9.6%
- B400 SR: -11.1%
- B200 IR: -9.5%
- HDL cholesterol decreases were noted but remained within normal ranges:
- OCA/B400 SR: -17.9%
- OCA/B200 IR: -14.9%

Sangeeta Sawhney, Senior Vice President and Head of U.S. Research & Development, emphasized the importance of these findings. She noted that ongoing studies continue to explore various doses and formulations of the OCA-bezafibrate combination to enhance clinical outcomes for PBC patients.

Intercept is focused on developing innovative therapies for rare liver diseases, including PBC. The company markets OCA in the U.S. under the brand name Ocaliva. While bezafibrate is not approved in the U.S., it shows potential when combined with OCA.

Primary biliary cholangitis is a rare, chronic autoimmune liver disease that predominantly affects women over 40. If untreated, it can lead to severe liver complications, including cirrhosis and the need for a liver transplant.

Ocaliva, an FXR agonist, is approved for treating adults with PBC, either in combination with UDCA for those with an inadequate response or as a monotherapy for those unable to tolerate UDCA. Approval was granted based on its ability to reduce ALP levels, with ongoing studies required to confirm its long-term benefits.

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