Arisaph Pharmaceuticals Reports Positive Results From Two Safety Clinical Trials For Its Niacin Analog (ARI-3037MO)
BOSTON, Nov. 7, 2012 /PRNewswire/ --
ARI-3037MO was well tolerated in single and repeat ascending
dose trials in healthy volunteers
ARI-3037MO did not provoke flushing or any other treatment-related
adverse effects in 58 healthy male and female volunteers
ARI-3037MO was well absorbed orally and plasma levels demonstrated
good dose proportionality
ARI-3037MO showed encouraging lipid changes in both clinical trials
in healthy subjects
Arisaph Pharmaceuticals, Inc. announced today during an oral
presentation at the American Heart Association (AHA) meeting in Los
Angeles, CA that its niacin analog, ARI-3037MO, was extremely well
tolerated in a single-ascending dose (SAD) and a multiple-ascending
dose (MAD) trial in healthy male and female volunteers. The
results showed that ARI-3037MO did not provoke flushing or any
other adverse skin changes, nor did it cause increases in liver
enzymes or blood glucose at doses up to 6 grams per day. In both
clinical trials, ARI-3037MO also demonstrated encouraging lipid
effects. Based on these promising results, ARI-3037MO potentially
represents a transformational, new niacin-like option for treatment
of patients with dyslipidemia, especially in the setting of
metabolic syndrome, a disorder that afflicts as many as 70 million
Americans1.
(Logo: http://photos.prnewswire.com/prnh/20110321/NE69091LOGO )
"The absence of flushing and other niacin induced adverse events highlights a differentiated safety profile for our novel niacin analog," said Christopher P. Kiritsy, Co-Founder, President and Chief Executive Officer of Arisaph Pharmaceuticals. "Moreover, the evidence of lipid changes in such short duration trials in healthy volunteers shows that our preclinical efficacy data are translating and breeds optimism for the development of our best-in-class niacin analog."
In two placebo controlled, safety and pharmacokinetic trials (SAD and MAD), 58 healthy male and female volunteers were given either single escalating doses of ARI-3037MO (up to 6 grams per day) or repeat escalating doses of ARI-3037MO (up to 3.5 grams per day) for 14 days. In both trials, ARI-3037MO was given once daily without a titration scheme. The results showed that ARI-3037MO was extremely well tolerated with no treatment-related adverse events. Specifically, treatment with ARI-3037MO did not show any evidence of flushing or adverse skin changes, such as itching or rash, using a validated visual-analog scale. Additionally, no deleterious changes in liver enzymes or blood glucose were observed with ARI-3037MO, even when given at high doses in a repeat-dose setting.
The pharmacokinetics of ARI-3037MO revealed that the drug was well absorbed orally and showed good dose proportionality. In both clinical trials, ARI-3037MO produced encouraging lipid signals. For example, a single dose of 6 grams of ARI-3037MO produced a 15% increase in HDL and attenuated the postprandial increase in serum triglycerides (TGs). In the MAD trial, the 2g and 3.5g doses of ARI-3037MO decreased LDL-cholesterol (LDL-C) from baseline and improved post-prandial triglycerides by more than 30% compared with placebo. Such lipid trends are encouraging considering that the trials were short-duration, safety and pharmacokinetic studies in healthy volunteers and would not be expected to show pharmacodynamic effects.
"Niacin's efficacy across a broad range of lipid risk factors has long been recognized but flushing and increases in blood glucose have limited its use, particularly in high risk metabolic syndrome patients," commented Dr. Ernst Schaefer, Professor of Medicine, Tufts University School of Medicine. "The results from these two safety trials show that ARI-3037MO is devoid of such dose-limiting side effects, resulting in a significantly improved safety and tolerability profile compared with other niacin-based therapies."
In preclinical studies presented at the AHA in 2011, ARI-3037MO showed robust changes in lipids, including LDL-C, HDL-C and triglycerides. For example, once-daily treatments of ARI-3037MO lowered LDL-C in excess of 50% and lowered TGs by more than 70% compared with placebo in high-fat-fed hamster models. Additionally, non-clinical toxicology studies conducted in dogs and rats with ARI-3037MO showed that high exposure multiples could be achieved without serious adverse events, even at doses greater than 1000 mg per kilogram. The favorable preclinical safety and efficacy data reveal that ARI-3037MO has an extremely wide therapeutic index, indicating that ARI-3037MO will not be dose limited by adverse events. Consequently, it is expected that patients will be able to achieve improved efficacy observed with higher doses of niacin.
About Niacin Analog Program:
The natural B vitamin niacin is a well-known lipid lowering agent,
which has been used to treat mixed lipid disorders for over 50
years. Niacin is a first-line drug for the treatment of
hyperlipidemia, and it is used in combination with statins to
further reduce LDL cholesterol and triglycerides or to increase HDL
cholesterol in patients with depressed HDL cholesterol
levels. Niacin can produce changes in HDL cholesterol up to
35%, lower LDL cholesterol up to 25% and lower triglycerides up to
50%. Despite niacin's broad lipid altering profile, the use
of niacin-based therapies is diminished because of unpleasant side
effects, particularly flushing. Flushing, representative of
tingling and/or redness of the skin, is the principal side effect
of niacin, and in some patients it can be extremely
uncomfortable. Arisaph has developed a novel class of
structural analogs of niacin that are expected to demonstrate a
dramatically improved safety and tolerability profile while
retaining the beneficial lipid effects associated with niacin.
About Arisaph
Arisaph Pharmaceuticals Inc, a drug discovery, biopharmaceutical
company located in Boston, Massachusetts, was founded by Dr.
William Bachovchin (Professor of Biochemistry, Tufts University
School of Medicine), Christopher Kiritsy (Former EVP Corporate
Development and CFO, Kos Pharmaceuticals, Inc.) and Michael Jaharis
(Founder, Chairman Emeritus, Kos Pharmaceuticals, Inc.) to develop
differentiated therapies for cardiometabolic diseases and cancer.
Arisaph has developed a rich pipeline of products at various stages
of development, including a niacin analog (ARI-3037MO), in phase 2
clinical development, and a small molecule immune modulator for the
treatment of cancer. The Company's vision is to create a fully
integrated pharmaceutical company, leveraging its drug discovery
expertise to develop transformational, patent protected, medicines
that offer distinct safety, efficacy and/or tolerability benefits
compared with existing therapies for large markets, whose needs are
not being fully met by current therapeutics.
Certain statements in this press release, including statements
regarding the Company's research and development effort, the
Company's expectation to initiate or complete human clinical
studies, the Company's ability to finance its development programs
into human clinical testing, and the Company's ability to
successfully capitalize on the early stage research are subject to
risks and uncertainties. These risks and uncertainties include
risks and uncertainties related to: our ability to discover
and develop new compounds and products using a novel approach to
drug discovery; the early stage of all of our discovery and
development efforts; our ability to complete preclinical and
clinical development of our products; our ability to obtain and
maintain regulatory approvals for our products; competition from
other technologies and technologies similar to ours; obtaining,
maintaining and protecting intellectual property utilized by our
products; changes in legislation and regulations affecting our
products and potential product candidates; our need to obtain
additional funding to support our business activities; our
dependence on collaborators and other third parties for
development, manufacture, marketing, sales and distribution of
products; the ability of our licensees to achieve developmental,
regulatory and other milestones and to commercialize their
products; the effect of conditions in the pharmaceutical industry
and the economy in general, as well as certain other risks and
uncertainties.
References:
1. NHANES Data, National Health Statistics Report, May 2009
Contact:
Arisaph Pharmaceuticals, Inc.
Christopher Kiritsy
President and CEO
(617) 986-4500
SOURCE Arisaph Pharmaceuticals, Inc.
Web Site: http://www.arisaph.com
Posted: November 2012
