Conatus Announces Results from ENCORE-PH Phase 2b Clinical Trial in NASH Cirrhosis
- Clinically Meaningful Improvements in Portal Hypertension in High Risk Compensated Cirrhosis Patients -
- Conference Call and Webcast Presentation at
The total patient population was composed of two prespecified subgroups – patients with compensated NASH cirrhosis (201 of 263 patients, or 76%) and patients with early decompensated NASH cirrhosis (62 of 263 patients, or 24%).
In patients with compensated NASH cirrhosis, post hoc analyses demonstrated consistent improvements in mean HVPG at week 24 over baseline. In these same patients, clinically meaningful differences compared with placebo in mean HVPG at Week 24 were observed in a consistent pattern over multiple baseline HVPG cohorts from ≥13 mmHg through ≥17 mmHg. The magnitude of the improvement in mean HVPG generally increased as the baseline HVPG levels increased. Both the 25mg and 50mg active dose groups achieved a >10% improvement in mean HVPG compared with placebo in all HVPG cohorts from ≥13 mmHg through ≥17 mmHg, while placebo-treated patients showed increases in mean HVPG. The greatest improvement was observed in patients with a baseline HVPG of 16 mmHg or higher.
“Patients with compensated cirrhosis and severe portal hypertension, that is, with HVPG of 12 mmHg or higher, are at risk for decompensation, that is, they are at risk for developing complications such as variceal hemorrhage, hepatic encephalopathy and ascites that significantly decrease their quality of life and survival,” said
The high-risk subgroup of compensated patients with HVPG ≥16 mmHg at baseline showed a clinically meaningful ≥2-point improvement in mean HVPG compared with placebo in all three emricasan dosing groups. A favorable trend compared with placebo in responses predictive of clinical benefit (≥20% reduction in HVPG from baseline) was also observed in the total ≥12 mmHg compensated patient population with the greatest responses observed in the ≥16 mmHg cohort. The baseline HVPG ≥16 mmHg cohort resembles the patient population studied in the prior Portal Hypertension pilot study and again shows, now in a placebo-controlled trial, a clinically meaningful improvement in mean HVPG. In addition, HVPG of ≥16 mmHg predicts a higher risk of both clinical events and death1.
“This trial evaluated the ability of emricasan to reduce HVPG in patients with cirrhosis due to NASH. Although the primary endpoint was not met, the data indicates an amelioration of portal pressures by emricasan,” said
Consistent with safety results from 17 previously completed clinical trials, emricasan was generally well-tolerated in the ENCORE-PH clinical trial, and the overall safety profile was similar in the emricasan and placebo groups. Patients enrolled in the ENCORE-PH clinical trial are continuing treatment or placebo in a six-month extension period to evaluate longer term safety, liver function and clinical outcomes, and results on the extension are expected in mid-2019.
“We believe data from the ENCORE-PH clinical trial as well as data from our two ongoing ENCORE trials that will be available in 2019 will warrant future discussions with regulatory authorities regarding potential pivotal trials in patients with NASH and advanced liver disease,” said
Conatus will host a conference call and webcast at
Emricasan is a first-in-class, orally active pan-caspase inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, caspase inhibitors have the potential to interrupt the progression of a variety of diseases. To date, emricasan has been studied in approximately 700 patients in 17 completed clinical trials across a broad range of liver diseases. In multiple Phase 2 clinical trials, emricasan has demonstrated clinically meaningful reductions in severe portal hypertension, improvements in measures of liver function, and evidence of an anti-fibrotic treatment effect, as well as rapid and sustained reductions in elevated levels of key biomarkers of inflammation and cell death, which play a role in the severity and progression of liver disease.
The randomized, double-blind ENCORE-PH Phase 2b clinical trial, initiated in the fourth quarter of 2016, enrolled 263 NASH patients with compensated or early decompensated liver cirrhosis and severe portal hypertension confirmed by HVPG of ≥12 mmHg at baseline. Patients were randomized 1:1:1:1 to receive 5 mg of emricasan, 25 mg of emricasan, 50 mg of emricasan, or placebo twice daily for 24 weeks. The trial was conducted at 75 U.S. and EU sites.
ENCORE-PH is one of three randomized, double-blind, placebo-controlled Phase 2b clinical trials being conducted by Conatus in collaboration with
- ENCORE-PH (for Portal Hypertension) six-month extension, with 48-week liver function and clinical outcome results expected in mid-2019;
- ENCORE-NF (for NASH Fibrosis), initiated in the first quarter of 2016, in approximately 330 patients with NASH fibrosis, with top-line results expected in the first half of 2019; and
- ENCORE-LF (for Liver Function), initiated in the second quarter of 2017, in approximately 210 patients with decompensated NASH cirrhosis, with top-line results expected in mid-2019.
Conatus is a biotechnology company focused on the development of novel medicines to treat liver disease. In collaboration with
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding: separate registration trials being needed in compensated and decompensated NASH cirrhosis; emricasan’s potential to provide clinical benefit; the timeline to announce results from the extension phase of the ENCORE-PH trial in mid-2019; the data from the ENCORE-PH, ENCORE-NF and ENCORE-LF trials warranting future discussions with regulatory authorities regarding pivotal trials; the timelines to announce results from the ongoing ENCORE clinical trials; and caspase inhibitors’ potential to interrupt the progression of a variety of diseases. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: reported top-line results are based on preliminary analysis of key data and as a result, such top-line results may change following a more comprehensive review and may not accurately reflect the complete results of the clinical trial; Conatus’ ability to successfully enroll patients in and complete its ongoing clinical trials;
1 Berzigotti A et al. Prognostic value of a single HVPG measurement and Doppler-ultrasound evaluation in patients with cirrhosis and portal hypertension. J Gastroenterol 2011. DOI: 10.1007/s00535-010-0360-z.
Turco L et al. Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis. J Hepatol 2018. DOI: 10.1016/j.jhep.2017.12.027.
CONTACT: Alan Engbring
Source: Conatus Pharmaceuticals Inc.