- Safety, Tolerability and Pharmacokinetics (“PK”) Primary Endpoints Met
- Reductions in Liver Transaminases Indicate Dose-Related Improvements in Key NASH Biomarker
- Concentration-Effect Relationship Demonstrated for ALT Reductions
- Multiomic Analyses and Machine Learning Paving the Way for Phase 2b, Anticipated to Start Later in 2021
EDISON, N.J., July 13, 2021 — Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on the development of therapeutic drugs for the treatment of liver disease arising from non-alcoholic steatohepatitis (“NASH”), today announced positive topline results from its Phase 2a ‘AMBITION’ NASH clinical trial. All primary endpoints of the trial were met.
AMBITION was a Phase 2a randomized, multi-center, placebo controlled, single-blind trial designed to investigate once daily oral administration of Rencofilstat at doses of 75 mg and 225 mg administered as soft gelatin capsules to presumed F2 and F3 NASH subjects for 28 days, followed by a 14-day observation period for safety.
The primary outcome measure of the AMBITION trial was the incidence of safety and tolerability events of Rencofilstat versus placebo. Rencofilstat at both study doses was well tolerated, and there were no serious adverse events (“SAEs”), and the few adverse events (“AEs”) observed were mostly mild and unrelated to study drug.
In the AMBITION trial, Rencofilstat blood concentrations after oral dosing of either 75 mg or 225 mg once daily were in the anticipated effective range for NASH treatment. The drug reached maximum concentrations within two hours after dosing with an effective half-life of approximately 30 hours, which supports once daily dosing.
It has been reported in recent literature that reductions in serum alanine aminotransferase (“ALT”) may be used as a surrogate measure for histologic improvement in NASH.1,2 The AMBITION trial did not include liver biopsies, however early indications of efficacy in the form of ALT reductions were observed with both Rencofilstat dosing cohorts. The percent ALT change from baseline to Day 28 numerically demonstrated a Rencofilstat versus placebo dose-response. These declines were statistically significant from placebo (p < 0.05) when Rencofilstat doses were pooled. Area-under-the ALT-Curve (“AUC”) for ALT changes, which has been useful in evaluating the magnitude of effect for clinical laboratory measurements of transaminases in NASH, was also calculated. As set out in the table below, Rencofilstat demonstrated decreasing ALT AUCs with increasing dose, indicating a positive dose-response. In addition, the 225 mg cohort ALT AUC was statistically different from the placebo group AUC.
| Test | Placebo (n=14) |
Rencofilstat 75 mg (n=12) |
Rencofilstat 225 mg (n=15) |
| ALT (% change) | -6.1±13.3 (mean±SD) -5.2 (median) |
-18.4±25.8 (mean±SD)* -15.9 (median) |
-21.1±21.1 (mean±SD)* -20.0 (median) |
| Area-Under-the-ALT-Curve (AUC) (IU*D/L) |
1465.1 ± 810.9 | 1190.5 ± 712.1 | 859.9 ± 387.0** |
* Pooled 75 mg & 225 mg statistically significant from placebo, p < 0.05, unpaired t-test.
**Statistically significant from placebo, p < 0.05, ANOVA with Bonferroni Post-Hoc
“The observed changes in serum ALT at this early timepoint, along with the safety and tolerability data are very encouraging and suggest a potential positive impact of Rencofilstat on hepatocyte health relative to placebo,” commented Stephen Harrison, MD, Principal Investigator of the AMBITION study, Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University. “I am eagerly anticipating additional biomarker data for this cohort and am hopeful to see corroborating evidence of a biochemical effect. Given the chronic nature of this disease, long-term therapy is likely going to be needed and, therefore, a therapy that is well tolerated, oral and once daily would be advantageous.”
“Statistical significance in a dose response on ALT is very encouraging, suggesting a rapid drug effect. A thorough review of literature by our group suggested that a 10% to 15% decline in ALT in four weeks over placebo would indicate a beneficial drug effect,” stated Patrick Mayo, Ph.D., Hepion’s SVP, Clinical Pharmacology and Analytics. “Our clinical pharmacology group has already developed a population pharmacokinetic-pharmacodynamic, or PK-PD, model which predicts Rencofilstat blood concentration effect on ALT reductions, which is not usually possible at this early stage in drug development. Additionally, preliminary transcriptomic and lipidomic analyses further support a drug effect when Rencofilstat blood concentrations exceed 800 ng/mL. This Phase 2a study confirmed Rencofilstat tolerability and successfully elucidated drug dose range for the upcoming Phase 2b trial.”
“In order to embark on a phase 2b program in NASH, these results were critical to inform us on many key parameters for use of Rencofilstat in this patient population,” said Todd Hobbs, MD, Hepion’s Chief Medical Officer. “Despite the challenges of starting clinical research during the COVID pandemic, the team was able to successfully complete this important trial. We look forward to the start of the large Phase 2b ‘ASCEND-NASH’ trial later this year, which will evaluate Rencofilstat in biopsy-proven NASH subjects with advanced fibrosis.”
“Rencofilstat is a cyclophilin inhibitor that represents a new approach to treating NASH,” commented Robert Foster, PharmD, Ph.D., Hepion’s CEO. “Rencofilstat is extensively extracted by the liver after oral dosing and, as such, its potential in treating liver disease is heavily dependent on liver function. We know that liver function declines with NASH, so it was important to design a study to delineate the effects of NASH on the safety, tolerability and PK of Rencofilstat. In addition, this study gave us an opportunity to explore the efficacy potential of Rencofilstat in NASH subjects. The current findings support this potential, and we will continue to analyze additional incoming data from this trial which should allow us to better understand Rencofilstat. We expect this additional data from the AMBITION trial in the near-term and will report it once we complete our analyses.”
1Hoofnagle, JH, et al. Aliment Pharmacol Ther. 2013; 38:134-143.
2Loomba, R. Clin Gastroenterol Hepatol. 2014; 12:1731-1732.
About Hepion Pharmaceuticals
The Company’s lead drug candidate, Rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat is currently in clinical-phase development for the treatment of NASH, with the potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH; and has demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms, in nonclinical studies.
Hepion has created a proprietary AI platform, called AI-POWR™, which stands for Artificial Intelligence – Precision Medicine; Omics (including genomics, proteomics, metabolomics, transcriptomics, and lipidomics); World database access; and Response and clinical outcomes. Hepion intends to use AI-POWR™ to help identify which NASH patients will best respond to Rencofilstat, potentially shortening development timelines and increasing the delta between placebo and treatment groups. In addition to using AI-POWR™ to drive its ongoing Phase 2a NASH program, Hepion will use the platform to identify additional potential indications for Rencofilstat to expand the company’s footprint in the cyclophilin inhibition therapeutic space.
Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2020 and other periodic reports filed with the Securities and Exchange Commission.
For further information, please contact:
Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com
