Stock Update (NASDAQ:CNAT): Conatus Pharmaceuticals Inc Extends Positive Results with Emricasan in Phase 2 Liver Cirrhosis Clinical Trial


Conatus Pharmaceuticals Inc (NASDAQ:CNAT) announced positive top-line results from the three-month, open-label second stage of the company’s multicenter Phase 2 clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, in patients with liver cirrhosis. Top-line results from the three-month placebo-controlled first stage of the trial were released in January. In the second stage, patients on emricasan in the first stage continued treatment for another three months, and patients on placebo in the first stage switched over to emricasan for three months.

  • Key measures of liver function showed continued directional improvements after the second three months of treatment on emricasan in the overall patient population following previously reported favorable trends with emricasan vs. placebo after the first three months.
  • Key measures of liver function showed continued directional improvements after the second three months of treatment on emricasan in a subgroup of patients with baseline Model for End-stage Liver Disease (MELD)1 scores ≥15, a prerequisite for a patient receiving a liver transplant, following previously reported statistically significant emricasan treatment effects vs. placebo after the first three months.
  • Regardless of baseline MELD score, patients whose cirrhosis was caused by nonalcoholic steatohepatitis (NASH) achieved statistically significant treatment effects vs. placebo on key measures of liver function after the first three months — making emricasan the first drug to demonstrate liver function benefit in patients with NASH cirrhosis. Directional improvements continued after the second three months of treatment.
  • A conference call and webcast are scheduled for 8:00 a.m. ET on Thursday, May 5, as detailed below, to discuss both the Liver Cirrhosis clinical trial results and first quarter 2016 financial results to be released before the call.

Continued Directional Improvements in Overall Patient Population

Two clinically relevant measures of liver function and prognosis, MELD score and Child-Pugh-Turcotte (Child-Pugh)2 score, along with other key liver function parameters which demonstrated favorable trends in emricasan treatment effects vs. placebo (improvement in the emricasan group vs. progression in the placebo group) in the overall patient population after three months of treatment showed continued directional improvement after six months of treatment.

Overall Patient Population Placebo (N=42) Emricasan (N=44) Month 3
p-value*
Baseline Change at
Month 3
Baseline Change at
Month 3
Change at
Month 6
MELD score 12.9 +0.1 12.8 ‒0.1 ‒0.3 0.466
Child-Pugh score 6.9 +0.1 6.9 ‒0.2 ‒0.3 0.124
Total bilirubin (mg/dL) 2.59 +0.07 2.25 ‒0.05 ‒0.05 0.209
INR 1.31 +0.02 1.33 ‒0.02 ‒0.04 0.117
Albumin (g/dL) 3.48 +0.06 3.46 +0.02 +0.06 0.440
*p-values for treatment effect at Month 3, based on adjusted LSMeans from the primary ANCOVA model with baseline value and treatment group; not adjusted for multiple testing.
†Based on last observation carried forward.

Key Exploratory Subgroup Results

Statistically significant emricasan treatment effects vs. placebo (improvement in the emricasan group vs. progression in the placebo group) after the first three months in a subgroup of patients with baseline MELD scores ≥15 showed continued directional improvements after the second three months.

Baseline MELD Score ≥15 Patient Population Placebo (N=10) Emricasan (N=9) Month 3
p-value*
Baseline Change at
Month 3
Baseline Change at
Month 3
Change at
Month 6
MELD score 16.3 +0.6 16.0 ‒1.6 ‒2.8 0.003
Child-Pugh score 8.2 +0.6 7.8 ‒0.6 ‒0.7 0.003
Total bilirubin (mg/dL) 4.30 ‒0.06 3.17 ‒0.55 ‒0.65 0.029
INR 1.45 +0.06 1.54 ‒0.14 ‒0.21 <0.001
Albumin (g/dL) 3.19 +0.05 3.41 +0.07 +0.10 0.779
*p-values for treatment effect at Month 3, based on adjusted LSMeans from the secondary ANCOVA model with baseline value, treatment group, baseline MELD category, etiology, treatment and MELD category interaction, and treatment and etiology interaction; not adjusted for multiple testing.
†Based on last observation carried forward.

In patients whose liver cirrhosis was caused by NASH, statistically significant emricasan treatment effects vs. placebo (slower progression in the emricasan group than in the placebo group) on measures of liver function after the first three months showed continued directional improvement after the second three months.

NASH Patient Population Placebo (N=9) Emricasan (N=11) Month 3
p-value*
Baseline Change at
Month 3
Baseline Change at
Month 3
Change at
Month 6
MELD score 12.8 +1.0 13.0 +0.3 +0.1 0.029
Child-Pugh score 6.9 +0.4 7.3 ‒0.3 ‒0.1 0.030
Total bilirubin (mg/dL) 2.26 +0.39 2.68 +0.09 ‒0.03 0.265
INR 1.27 +0.07 1.25 +0.01 0.00 0.017
Albumin (g/dL) 3.60 +0.11 3.39 +0.05 +0.03 0.645
*p-values for treatment effect at Month 3, based on adjusted LSMeans from the secondary ANCOVA model with baseline value, treatment group, baseline MELD category, etiology, treatment and MELD category interaction, and treatment and etiology interaction; not adjusted for multiple testing.
†Based on last observation carried forward.

Consistent with the company’s previous 15 clinical trials, emricasan was generally well-tolerated in the Liver Cirrhosis clinical trial, and the overall safety profile was similar in the emricasan and placebo groups with regard to both serious and other adverse events.

“We were highly encouraged after the first three months of treatment, in patients with cirrhosis and impaired hepatic function, by the favorable overall trends in two clinically relevant measures of liver function and prognosis — MELD and Child Pugh scores — which clearly were driven by statistically significant improvements in the high baseline MELD score subgroup,” said David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus. “The continued directional improvements in these measures of liver function after six months of treatment confirm the sustained activity of emricasan and support continued development in patients with cirrhosis. The statistically significant treatment effects in the NASH patient subgroup, which applied regardless of baseline MELD scores, offer a greater range of options for future clinical trials in patients with NASH cirrhosis.”

“We are pleased to confirm and extend the positive results from our Phase 2 Liver Cirrhosis trial,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D., “with favorable trends in measures of liver function in the overall patient population and significant treatment effects in the high-MELD population after three months, both with continued directional improvements after six months and a reassuring safety and tolerability profile consistent with our prior experience. Our Portal Hypertension trial and Liver Cirrhosis trial have demonstrated emricasan’s rapid and meaningful activity against all three potentially acceptable validated surrogate endpoints identified by the FDA (U.S. Food and Drug Administration) for clinical trials in patients with liver cirrhosis. The subgroup analysis of NASH patients in the Liver Cirrhosis trial provided the first ever demonstration in NASH cirrhosis of liver function benefit in response to drug treatment. We believe this benefit, along with our Fast Track designation by the FDA in NASH cirrhosis, provides strong support to focus on an initial registration of emricasan in NASH cirrhosis. We intend to discuss these results and plans for the ENCORE-LF clinical trial in patients with NASH cirrhosis with regulatory authorities in the coming months as we advance toward trial initiation in early 2017.”

Liver Cirrhosis Trial
The double-blind, placebo-controlled Phase 2 Liver Cirrhosis clinical trial was conducted at 26 U.S. sites and enrolled 86 patients with liver cirrhosis due to different etiologies, mild to moderate liver impairment and baseline MELD scores of 11 to 18. In the double-blind and placebo-controlled stage, patients were randomized 1:1 to receive either 25 mg of emricasan or placebo orally twice daily for three months. The primary endpoint was change from baseline in cCK18 at three months. Secondary endpoints included changes from baseline in MELD and Child-Pugh scores, which include laboratory parameters associated with liver synthetic and excretory function, such as serum albumin levels, international normalized ratio (INR) and total bilirubin levels. In the open-label stage, all patients either on emricasan or placebo received emricasan for an additional three months.

Among the 86 subjects enrolled and dosed, liver cirrhosis etiologies included alcohol (38%), hepatitis C virus, or HCV (29%), NASH (23%), and other causes (9%). Baseline MELD scores were ≤14 in 78% of enrolled subjects and ≥15 in 22% of enrolled subjects. Baseline Child-Pugh status was A (Child-Pugh score of 5-6) in 43% of subjects and B (Child-Pugh score of 7-9) in 56% of subjects. (Original Source)

Shares of Conatus are up nearly 21% to $3.29 in after-hours trading. CNAT has a 1-year high of $7.12 and a 1-year low of $1.40. The stock’s 50-day moving average is $2.62 and its 200-day moving average is $2.64.

On the ratings front, Conatus has been the subject of a number of recent research reports. In a report issued on April 15, FBR analyst Vernon Bernardino reiterated a Buy rating on CNAT. Separately, on March 10, Brean Murray Carret’s Difei Yang maintained a Buy rating on the stock and has a price target of $13.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Vernon Bernardino and Difei Yang have a total average return of -17.9% and -13.2% respectively. Bernardino has a success rate of 27.0% and is ranked #3813 out of 3838 analysts, while Yang has a success rate of 32.0% and is ranked #3803.

Conatus Pharmaceuticals, Inc. operates as a biotechnology company, which engages in the development and commercialization of novel medicines to treat liver diseases. It develops lead compound, emricasan, for the treatment of patients in orphan populations with chronic liver disease and acute exacerbations of chronic liver disease. The company was founded by Alfred P. Spada, Jennifer Giottonini Cayer, Steven J. Mento and Charles J. Cashion on July 13, 2005 and is headquartered in San Diego, CA.