- Low dose atorvastatin rapidly reversed
OCA associated LDL changes
Conference call scheduled for 8:30 am
ET
Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a
biopharmaceutical company focused on the development and
commercialization of novel therapeutics to treat progressive
non-viral liver diseases, today announced results from CONTROL, a
placebo-controlled trial to prospectively characterize the lipid
metabolic effects of obeticholic acid (OCA) and concomitant statin
administration in patients with nonalcoholic steatohepatitis (NASH)
with fibrosis or cirrhosis. The CONTROL trial met its primary
objective by showing that newly initiated treatment with
atorvastatin rapidly reversed OCA-associated increases in LDL to
below baseline levels. Most of the effect was observed four weeks
after initiation of the lowest available dose of atorvastatin and
was sustained throughout the study period.
CONTROL is a 16-week double-blind, placebo-controlled,
dose-ranging study of 84 NASH patients with fibrosis and
compensated cirrhosis, followed by a two-year long term safety
extension (LTSE) open label phase which is currently ongoing. Lipid
changes were assessed every four weeks over the course of the
double-blind phase. Details of the study design are as follows:
- Statin-naïve or washout patients were randomized to receive one
of three doses of OCA (5 mg, 10 mg or 25 mg) or placebo.
- At week four, the lowest approved dose of atorvastatin (10 mg)
was added in all patients.
- At week eight, patients were titrated to the next highest
prescribed dose of atorvastatin (20 mg).
- At week 12, further titration of atorvastatin (up to 40 mg) was
permitted at investigators’ discretion.
The study was designed to measure treatment differences within
each group relative to baseline. The intent-to-treat (ITT) analysis
is shown below and includes all patients who received at least one
dose of study medication.
At week four, mean LDL levels increased in each of the OCA
treatment groups, while remaining relatively unchanged in the
placebo group. The addition of 10 mg of atorvastatin rapidly
reversed mean LDL to below baseline levels in all OCA treatment
groups at the first assessed time point (week eight), and this
effect was sustained through week 16. The observed mean LDL
reductions in the OCA groups were approximately 40 – 45 mg/dL while
placebo was 48 mg/dL.
(mg/dL) |
Placebo (N=21) |
OCA 5 mg (N=20) |
OCA 10 mg (N=21) |
OCA 25 mg (N=22) |
Mean LDL at Baseline |
118 |
135 |
122 |
126 |
Mean LDL at Week 4 |
113 |
153 |
141 |
158 |
Mean LDL at Week 8 (+ atorvastatin 10 mg) |
75 |
96 |
91 |
93 |
Mean LDL at Week 16 (+ atorvastatin 10 – 40 mg) |
70 |
95 |
82 |
85 |
Mean LDL Change from Baseline at Week 16 |
-48 |
-40 |
-40 |
-45 |
The primary
efficacy analysis was based on the efficacy evaluable (EE)
population, defined as those patients who completed the
double-blind phase and received all doses of OCA and atorvastatin
(n=67). The overall results for the ITT population were similar to
those in the EE population. |
Lipid sub-fraction analysis showed that OCA-related increases in
LDL were primarily driven by an increase in large buoyant LDL
particles rather than small dense LDL particles. Changes in other
lipid parameters were similar to those previously reported with OCA
therapy in patients with NASH.
Mild to moderate pruritus was the most common adverse event in
patients treated with OCA, occurring in 5%, 5%, 10% and 55% in
placebo, 5 mg, 10 mg and 25 mg OCA groups, respectively. Two
patients discontinued treatment in the 25 mg OCA treatment arm due
to pruritus. Co-administration of atorvastatin and OCA was
generally well tolerated and did not result in any unexpected
safety observations.
The proportion of patients completing the double-blind period
was similar across treatment groups (100%, 95%, 90% and 91% for
placebo, OCA 5 mg, OCA 10 mg and OCA 25 mg, respectively). Of these
patients, 77 of 79 (97%) chose to participate in the LTSE phase.
During the ongoing LTSE phase, there has been one patient death
due to acute renal and liver failure. While Intercept determined it
could not be ruled out that this was possibly related to treatment,
the principal investigator and the independent Data Safety
Monitoring Committee determined the death was unlikely related to
OCA.
“The majority of NASH patients in CONTROL were statin eligible
according to AHA treatment guidelines, and statins are recommended
for patients with NASH in both AASLD and EASL treatment
guidelines,” said David Shapiro, M.D., Chief Medical Officer of
Intercept. “In CONTROL, we have shown that statin therapy can have
an important role in managing LDL when co-administered with OCA in
NASH patients with fibrosis and cirrhosis.”
Conference Call on July 31st at 8:30 a.m. ET
Intercept will discuss the CONTROL results during its second
quarter 2017 financial results conference call and webcast on July
31st at 8:30 a.m. ET. The live event will be available on the
investor page of Intercept's website at
http://ir.interceptpharma.com or by calling (855) 232-3919
(toll-free domestic) or (315) 625-6894 (international) five minutes
prior to the start time (no passcode is required). A replay of the
call will be available on Intercept's website approximately two
hours after the completion of the call and will be archived for two
weeks.
About CONTROLCONTROL is a randomized,
double-blind, placebo-controlled trial to characterize the lipid
metabolic effects of OCA and cholesterol management effects of
concomitant statin administration in NASH patients. CONTROL
enrolled 84 NASH patients who were naïve to statin therapy or
underwent a statin washout, and includes a 16-week double-blind
phase followed by an optional two-year long-term safety extension
phase.
About Nonalcoholic SteatohepatitisNASH is a
serious progressive liver disease caused by excessive fat
accumulation in the liver that induces chronic inflammation,
resulting in progressive fibrosis (scarring) that can lead to
cirrhosis, eventual liver failure, cancer and death. There are
currently no medications approved for the treatment of NASH. The
proportion of liver transplants attributable to NASH has increased
rapidly in past years and by 2020 the disease is projected to
become the leading indication for liver transplant.
About InterceptIntercept is a biopharmaceutical
company focused on the development and commercialization of novel
therapeutics to treat progressive non-viral liver diseases,
including primary biliary cholangitis (PBC), nonalcoholic
steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and
biliary atresia. Founded in 2002 in New York, Intercept now has
operations in the United States, Europe and Canada. For more
information about Intercept, please visit
www.interceptpharma.com.
Safe Harbor Statements This press release
contains "forward-looking statements" within the meaning of the
Private Securities Litigation Reform Act of 1995, including, but
not limited to, statements regarding the effective management of
LDL increases in NASH from OCA treatment with the use of statins,
the potential utility of the results from CONTROL, the prevalence
of NASH and NAFLD, the association of type 2 diabetes and fibrosis
with increased risk in NASH patients, the potential of OCA to treat
patients with NASH, and our strategic directives under the caption
"About Intercept." These "forward-looking statements" are based on
management's current expectations of future events and are subject
to a number of important risks and uncertainties that could cause
actual results to differ materially and adversely from those set
forth in or implied by such forward-looking statements. These risks
and uncertainties include, but are not limited to: the potential
benefit and commercial potential of Ocaliva in PBC, and Intercept's
ability to maintain its regulatory approval in jurisdictions in
which Ocaliva is approved for use in PBC; the initiation, cost,
timing, progress and results of Intercept's development activities,
preclinical studies and clinical trials; the timing of and
Intercept's ability to obtain and maintain regulatory approval of
OCA in PBC in countries outside the ones in which it is approved
and in indications other than PBC and any other product candidates
it may develop such as INT-767; conditions that may be imposed by
regulatory authorities on Intercept's marketing approvals for its
products and product candidates such as the need for clinical
outcomes data (and not just results based on achievement of a
surrogate endpoint), and any related restrictions, limitations,
and/or warnings in the label of any approved products and product
candidates; Intercept's plans to research, develop and
commercialize its product candidates; Intercept's ability to obtain
and maintain intellectual property protection for its products and
product candidates; Intercept's ability to successfully
commercialize its products and product candidates; the size and
growth of the markets for Intercept's products and product
candidates and its ability to serve those markets; the rate and
degree of market acceptance of any of Intercept's products, which
may be affected by the reimbursement received from payors; the
success of competing drugs that are or become available; regulatory
developments in the United States and other countries; the
performance of third-party suppliers and manufacturers; the
election by Intercept's collaborators to pursue research,
development and commercialization activities; Intercept's ability
to attract collaborators with development, regulatory and
commercialization expertise; Intercept's need for and ability to
obtain additional financing; Intercept's estimates regarding
expenses, revenues and capital requirements and the accuracy
thereof; Intercept's use of cash and short-term investments;
Intercept's ability to attract and retain key scientific or
management personnel; and other factors discussed under the heading
"Risk Factors" contained in our annual report on Form 10-K for the
year ended December 31, 2016 filed on March 1, 2017 as well as any
updates to these risk factors filed from time to time in our other
filings with the Securities and Exchange Commission. All
information in this press release is as of the date of the release,
and Intercept undertakes no duty to update this information unless
required by law.
Contact
For more information about Intercept Pharmaceuticals, please contact:
Mark Vignola
+1-646-747-1000
investors@interceptpharma.com
Christopher Frates
+1-646-757-2371
media@interceptpharma.com
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