– Emricasan Significantly Lowered Portal Pressure in Patients With Severe Portal Hypertension –
– Conference Call and Webcast Presentation at 8:30 a.m. ET on Thursday, September 24 –
SAN DIEGO, CA, USA I September 23, 2015 I Conatus Pharmaceuticals Inc. (CNAT) today announced that the company’s exploratory Phase 2 Portal Hypertension (PH) clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, met the following primary endpoints: a) a clinically meaningful and statistically significant change from baseline in hepatic venous pressure gradient (HVPG), a measurement of pressure in the portal vein, in patients with liver cirrhosis and severe portal hypertension (HVPG >=12 mmHg); and b) a statistically significant change from baseline in cleaved Cytokeratin 18 (cCK18), a mechanism-specific biomarker of excessive cell death that contributes to chronic inflammation, in the total evaluable liver cirrhosis patient population.
The open-label PH trial was conducted at nine U.S. sites and enrolled 23 patients (22 evaluable) with portal hypertension and compensated liver cirrhosis that was predominantly due to nonalcoholic steatohepatitis (NASH) or hepatitis C virus (HCV), including patients with active HCV infection and patients who had a sustained viral response (SVR) to antiviral therapy. Portal hypertension, or elevated blood pressure in the major vein feeding into the liver, was confirmed by HVPG measurement >5 mmHg at baseline and measured again after treatment with 25 mg of emricasan orally twice daily for 28 days. Patients were divided according to the HVPG therapeutic threshold of 12 mmHg, which indicates more severe portal hypertension. Reducing the HVPG to below 12 mmHg or reducing HVPG by >=10% or >=20% has been strongly associated with clinical benefit in this patient population.
The HVPG endpoint was analyzed in: a) patients with baseline HVPG values >=12 mmHg (N=12); b) patients with baseline HVPG values <12 mmHg (N=10); and c) all evaluable patients (N=22). HVPG measurement was standardized, and tracings were evaluated by a single expert reader not otherwise involved in the PH trial. HVPG decreased by a mean of 3.7 mmHg from the mean baseline of 20.6 mmHg in the higher baseline HVPG group (p<0.003), with 8 of 12 achieving a >=10% decrease, 4 of 12 achieving a >=20% decrease, and 2 of 12 achieving reductions below 12 mmHg. The changes from baseline HVPG were not statistically significant in the lower baseline HVPG group (+1.9 mmHg mean increase from mean baseline of 8.1 mmHg; p=0.12) or the total evaluable patient population (–1.1 mmHg from mean baseline of 15.2 mmHg; p=0.26). The cCK18 endpoint, analyzed in the total evaluable patient population, showed a statistically significant reduction (p<0.03) from baseline. Consistent with results from prior trials, emricasan was safe and well tolerated in the PH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Detailed results are expected to be presented in a future scientific forum.
As liver cirrhosis progresses, portal pressure increases and hepatic function is eventually lost. Importantly, portal hypertension is largely responsible for events of hepatic decompensation including variceal bleeding, ascites, and encephalopathy, which contribute substantially to morbidity and mortality in these patients. By lowering elevated portal pressures, emricasan has the potential to decrease the risk of hepatic decompensation in liver cirrhosis patients over the short term, and may improve both liver function and structure over the long term through anti-inflammatory and anti-fibrotic effects.
David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus, said, “We were excited to demonstrate that a drug candidate with the potential to achieve long-term resolution of fibrosis and cirrhosis also has the ability to induce a rapid and clinically meaningful reduction of severe portal hypertension. The reduction of portal pressure over a relatively short time frame in the patients with therapeutically relevant portal hypertension may reflect the initial impact of emricasan on the hyperdynamic circulation that is the predominant contributor to portal hypertension as cirrhosis progresses and/or a direct effect upon intrahepatic vasculature resistance. Future studies will be needed to assess the relative contribution of these mechanisms to the observed clinical effect. Decreasing HVPG has been identified by the FDA (U.S. Food and Drug Administration) as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis. These results set the stage for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension.”
“These results demonstrate that emricasan can cause a clinically meaningful improvement in portal hypertension in the liver cirrhosis patients who need it most,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “Specifically, patients with therapeutically relevant baseline portal hypertension showed meaningful decreases in HVPG. We believe the results from this trial establish the near-term effects of emricasan on portal hypertension. We are evaluating emricasan’s potential longer-term effects on liver function and liver structure in our other two ongoing clinical trials: the Phase 2 Liver Cirrhosis (LC) trial and the Phase 2b post-transplant trial.”
“Even though the number of patients in this trial was small,” added Dr. Hagerty, “Conatus was encouraged by the consistency of responses in patients with portal hypertension and cirrhosis due primarily to NASH or HCV. These results further support our view that apoptosis and inflammation are important common mechanisms for progressive liver disease across multiple etiologies, and that treatment with emricasan is likely to provide both short- and long-term clinical benefits.”
Conference Call/Webcast/Presentation
Conatus will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, September 24, to discuss the top-line results and provide a mechanism-focused overview of liver cirrhosis and portal hypertension. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 45793794. An associated presentation and live and archived audio webcast of the call will be available in the Investor Center of the company’s website at http://ir.conatuspharma.com/events.cfm.
About Emricasan Clinical Development
To date, emricasan has been studied in over 600 subjects in fifteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company’s ongoing Phase 2 LC trial is evaluating emricasan’s potential medium-term effect on liver function using two other potential surrogate clinical endpoints — Model for End-Stage Liver Disease (MELD) score and Child-Pugh-Turcotte (CPT) status. The company also is evaluating emricasan’s potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a SVR following HCV antiviral therapy (POLT-HCV-SVR). The company currently is developing a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis.
About Conatus Pharmaceuticals
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. 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, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.
SOURCE: Conatus Pharmaceuticals
Post Views: 117
– Emricasan Significantly Lowered Portal Pressure in Patients With Severe Portal Hypertension –
– Conference Call and Webcast Presentation at 8:30 a.m. ET on Thursday, September 24 –
SAN DIEGO, CA, USA I September 23, 2015 I Conatus Pharmaceuticals Inc. (CNAT) today announced that the company’s exploratory Phase 2 Portal Hypertension (PH) clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, met the following primary endpoints: a) a clinically meaningful and statistically significant change from baseline in hepatic venous pressure gradient (HVPG), a measurement of pressure in the portal vein, in patients with liver cirrhosis and severe portal hypertension (HVPG >=12 mmHg); and b) a statistically significant change from baseline in cleaved Cytokeratin 18 (cCK18), a mechanism-specific biomarker of excessive cell death that contributes to chronic inflammation, in the total evaluable liver cirrhosis patient population.
The open-label PH trial was conducted at nine U.S. sites and enrolled 23 patients (22 evaluable) with portal hypertension and compensated liver cirrhosis that was predominantly due to nonalcoholic steatohepatitis (NASH) or hepatitis C virus (HCV), including patients with active HCV infection and patients who had a sustained viral response (SVR) to antiviral therapy. Portal hypertension, or elevated blood pressure in the major vein feeding into the liver, was confirmed by HVPG measurement >5 mmHg at baseline and measured again after treatment with 25 mg of emricasan orally twice daily for 28 days. Patients were divided according to the HVPG therapeutic threshold of 12 mmHg, which indicates more severe portal hypertension. Reducing the HVPG to below 12 mmHg or reducing HVPG by >=10% or >=20% has been strongly associated with clinical benefit in this patient population.
The HVPG endpoint was analyzed in: a) patients with baseline HVPG values >=12 mmHg (N=12); b) patients with baseline HVPG values <12 mmHg (N=10); and c) all evaluable patients (N=22). HVPG measurement was standardized, and tracings were evaluated by a single expert reader not otherwise involved in the PH trial. HVPG decreased by a mean of 3.7 mmHg from the mean baseline of 20.6 mmHg in the higher baseline HVPG group (p<0.003), with 8 of 12 achieving a >=10% decrease, 4 of 12 achieving a >=20% decrease, and 2 of 12 achieving reductions below 12 mmHg. The changes from baseline HVPG were not statistically significant in the lower baseline HVPG group (+1.9 mmHg mean increase from mean baseline of 8.1 mmHg; p=0.12) or the total evaluable patient population (–1.1 mmHg from mean baseline of 15.2 mmHg; p=0.26). The cCK18 endpoint, analyzed in the total evaluable patient population, showed a statistically significant reduction (p<0.03) from baseline. Consistent with results from prior trials, emricasan was safe and well tolerated in the PH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Detailed results are expected to be presented in a future scientific forum.
As liver cirrhosis progresses, portal pressure increases and hepatic function is eventually lost. Importantly, portal hypertension is largely responsible for events of hepatic decompensation including variceal bleeding, ascites, and encephalopathy, which contribute substantially to morbidity and mortality in these patients. By lowering elevated portal pressures, emricasan has the potential to decrease the risk of hepatic decompensation in liver cirrhosis patients over the short term, and may improve both liver function and structure over the long term through anti-inflammatory and anti-fibrotic effects.
David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus, said, “We were excited to demonstrate that a drug candidate with the potential to achieve long-term resolution of fibrosis and cirrhosis also has the ability to induce a rapid and clinically meaningful reduction of severe portal hypertension. The reduction of portal pressure over a relatively short time frame in the patients with therapeutically relevant portal hypertension may reflect the initial impact of emricasan on the hyperdynamic circulation that is the predominant contributor to portal hypertension as cirrhosis progresses and/or a direct effect upon intrahepatic vasculature resistance. Future studies will be needed to assess the relative contribution of these mechanisms to the observed clinical effect. Decreasing HVPG has been identified by the FDA (U.S. Food and Drug Administration) as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis. These results set the stage for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension.”
“These results demonstrate that emricasan can cause a clinically meaningful improvement in portal hypertension in the liver cirrhosis patients who need it most,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “Specifically, patients with therapeutically relevant baseline portal hypertension showed meaningful decreases in HVPG. We believe the results from this trial establish the near-term effects of emricasan on portal hypertension. We are evaluating emricasan’s potential longer-term effects on liver function and liver structure in our other two ongoing clinical trials: the Phase 2 Liver Cirrhosis (LC) trial and the Phase 2b post-transplant trial.”
“Even though the number of patients in this trial was small,” added Dr. Hagerty, “Conatus was encouraged by the consistency of responses in patients with portal hypertension and cirrhosis due primarily to NASH or HCV. These results further support our view that apoptosis and inflammation are important common mechanisms for progressive liver disease across multiple etiologies, and that treatment with emricasan is likely to provide both short- and long-term clinical benefits.”
Conference Call/Webcast/Presentation
Conatus will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, September 24, to discuss the top-line results and provide a mechanism-focused overview of liver cirrhosis and portal hypertension. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 45793794. An associated presentation and live and archived audio webcast of the call will be available in the Investor Center of the company’s website at http://ir.conatuspharma.com/events.cfm.
About Emricasan Clinical Development
To date, emricasan has been studied in over 600 subjects in fifteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company’s ongoing Phase 2 LC trial is evaluating emricasan’s potential medium-term effect on liver function using two other potential surrogate clinical endpoints — Model for End-Stage Liver Disease (MELD) score and Child-Pugh-Turcotte (CPT) status. The company also is evaluating emricasan’s potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a SVR following HCV antiviral therapy (POLT-HCV-SVR). The company currently is developing a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis.
About Conatus Pharmaceuticals
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. 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, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.
SOURCE: Conatus Pharmaceuticals
Post Views: 117
