Omthera Pharmaceuticals Presents Successful Phase 3 Results from EVOLVE and ESPRIT Clinical Studies for Epanova™; Both Trials Meet Primary and Secondary Endpoints
Full Results to be Announced Today, Monday, November 5, 2012 at 7:30 am PST, at Company Presentation in Los Angeles and Available via Webcast and Replay at www.Omthera.com
Princeton, NJ, November 5, 2012 -- Omthera Pharmaceuticals, Inc., a privately held specialty pharmaceuticals company, today announced that Phase 3 results from its EVOLVE (EpanoVa fOr Lowering Very High triglyceridEs) and ESPRIT (Epanova combined with a Statin in Patients with HypertRiglycerIdemia to Reduce Non-HDL CholesTerol) clinical trials for Epanova™ met all primary and secondary endpoints. The full results from this more than 1,000 patient, global Phase 3 program, will be presented today via presentation and webcast by Dr. Michael Davidson, the Company's Chief Medical Officer and Co-founder. Epanova, the Company's lead compound for the treatment of patients with very high triglycerides, is a patent protected, novel, ultra-pure mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with high bioavailability, which could become the best-in-class therapy.
• Epanova significantly lowers triglycerides (TG) and reduces Non-HDL-C, widely believed to be the most accurate predictor of cardiovascular risk.
• Epanova's 2 gram dosage is comparable in efficacy across the key lipid parameters to the 4 gram dose of other prescription Omega 3 products.
• Upon approval, Epanova's 2 gram once-a-day dose will provide the lowest, most convenient dosing for patients and can be taken with or without meals, yielding better patient compliance.
• Epanova was also studied at a 4 gram once-a-day dose, allowing patients to titrate to this higher dose for greater TG and Non-HDL-C lowering efficacy. In the ESPRIT trial in patients with TG between 200 – 500 mg/dL, the 4 gram dose of Epanova provided a 7% reduction in Non-HDL-C and a 21% reduction in TG, with a non-significant increase in LDLC of 1%.
• Epanova's enhanced bioavailability produces substantially higher plasma levels of EPA and DHA, which may result in lower cardiovascular risk for patients.
• Phase 3 results show that Epanova has a positive impact on other markers of cardiovascular risk, including ApoC-III and LpPLA2.
• Epanova, at doses of 2 to 4 grams, once-a-day, was shown to be safe and well tolerated. Full data for both trials will be provided by Omthera's management team at a presentation being held this morning, November 5, 2012 at 7:30 a.m. pst at the Millennium Biltmore Hotel in Los Angeles and also available via live webcast. The webcast and replay of the event will both be available at www.Omthera.com.
Commenting on the positive results of these Phase 3 trials, Michael Davidson, MD, Chief Medical Officer and Co-Founder of Omthera, stated, "We are delighted by the wide-ranging lipid benefits shown by Epanova in both the EVOLVE and ESPRIT trials. Most notably, we are highly encouraged by the strong efficacy demonstrated by the 2 gram dose in significantly lowering triglycerides and Non-HDL-C, as well as established markers of cardiovascular risk for patients taking Epanova either as a monotherapy or in combination with statins."
John J. P. Kastelein, M.D., Ph.D., FESC, Professor of Medicine, Department of Vascular Medicine at the Academic Medical Center, University of Amsterdam, stated, "Epanova's 2 gram dose efficacy for triglyceride, non-HDL-C and ApoC-III reduction provides an effective and well tolerated therapy for an important unmet medical need in patients at high cardiovascular risk due to high triglycerides.
With a low starting dose, lack of food effect, and once-a-day dosing that can be readily combined with a statin, Epanova represents a significant improvement over existing prescription Omega-3 therapies. I believe that, if approved, Epanova will be the best-in-class Omega-3 prescription product."
The EVOLVE trial, a 12 week, multi-center, randomized, double-blind study of 399 patients, evaluated the efficacy and safety of three doses of Epanova in patients with fasting TG levels of at least 500 mg/dL but less than 2000 mg/dL. Patients were randomized into four dosing groups: Epanova 2g/day; Epanova 3g/day; Epanova 4g/day; and control (olive oil 4g/day). The study reached its primary endpoint of TG reduction (measured as a percentage change from baseline to week 12) as well as its secondary endpoint of Non-HDL-C at all doses. Specifically, Epanova:
• demonstrated highly statistically significant reduction of TG in all dose groups, with decreases in TG from baseline to end of treatment of approximately 26% (p<0.01) in the 2 gram cohort and 31% (p<0.001) for subjects on the 4 gram dose.
• demonstrated statistically significant reduction in Non-HDL-C in all dose groups, with decreases in Non-HDL-C of approximately 8% (p<0.05) in the 2 gram cohort and 10% (p<0.01) in the 4 gram cohort. Non-HDL-C is widely viewed as the most accurate predictor of cardiovascular disease.
• produced statistically significant reductions in multiple, established markers of atherogenicity (i.e., cardiovascular risk). Of note, treatment with Epanova yielded an approximate 11% (p<0.05) reduction in ApoC-III among subjects in the 2 gram cohort and an approximate 14% (p<0.001) reduction among subjects in the 4 gram cohort.
• showed substantially higher dose-dependent increases in plasma levels of EPA and DHA, confirming the superior bioavailability of this free fatty acid formulation versus the ethyl ester form found in other prescription Omega 3 products.
• was safe and well tolerated, with the most common treatment emergent adverse events being mild and GI in nature, most of which were resolved during the course of the study.
ESPRIT, a six-week, randomized, double-blind, parallel group study of 647 patients, assessed the efficacy and safety of add-on Epanova to statin therapy in patients with persistent
hypertriglyceridemia and high risk for cardiovascular disease. Patients were randomized into three dosing groups; Epanova 2g/day; Epanova 4g/day; and control (olive oil 4 g/day). The study met its primary endpoint, a percentage change in Non-HDL-C from baseline to week 6, as well as its secondary endpoints, including a percent change in TG and HDL-C from baseline to week 6.
Specifically, the study showed that Epanova (2g or 4g daily), when added to statin monotherapy:
• demonstrated a statistically significant reduction in Non-HDL-C in all dose groups, with decreases in Non-HDL-C from baseline to week 6 of approximately 4% (p<0.05) in the 2
gram cohort (comparable to doubling the statin dose) and approximately 7% (p<0.001) for subjects in the 4 gram cohort (comparable to tripling the statin dose for patients).
• demonstrated a statistically significant reduction in TG in all dose groups, with decreases in TG of approximately 15% (p<0.001) in the 2 gram cohort and 21% (p<0.001) for subjects in the 4 gram cohort.
• demonstrated a statistically significant reduction in VLDL-C of 14% with the 2 gram dose and a decrease of 22% with the 4 gram dose. LDL-C increased 5% with the 2 gram dose (5.0 mg/dL, p<0.05) and showed a 1% increase in LDL-C (1.0 mg/dL, NS) with the 4 gram dose. Non-HDL-C is primarily comprised of VLDL-C and LDL-C.
• produced significant reductions in multiple, established markers of atherogenicity. Specifically, at the 2 gram dose, Epanova yielded an approximate 8% (p<0.065) reduction in
ApoC-III, and an approximate 13% (p<0.0001) reduction in ApoC-III at the 4 gram dose.
• significantly increased plasma levels of EPA and DHA with both doses of Epanova.
• was safe and well tolerated, with mild, transient GI related adverse events.
Jerry Wisler, Chief Executive and Co-Founder of Omthera, added, "Four million patients in the U.S. currently suffer with severely high triglycerides and 40 million patients have high triglycerides, and this population is rapidly increasing. The ability to potentially take a once-a-day 2 gram dose, with or without meals, versus other prescription Omega-3s currently approved by the FDA, which do not offer these dosing options, would represent a tremendous advantage. The data from the EVOLVE and ESPRIT trials underscores our belief that, ultimately, Epanova will become the best-in-class, most convenient prescription Omega-3 on the market. With this data, we look forward to submitting Epanova for approval to the FDA."
Epanova is a patent protected, novel, ultra-pure mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omthera has developed a substantial body of data on Epanova, which points to an improved and more predictable bioavailability as compared to the ethyl ester form found in prescription Omega-‐3 products currently available.
Triglyceride lowering with Epanova was previously observed in two large, placebo-controlled, randomized, double-blind, Phase III studies involving 748 Crohn's disease patients with normal triglyceride levels for ≥52 weeks, approximately 400 of which were treated with Epanova for remission of disease. In all studies performed to date, Epanova has demonstrated a very good safety and tolerability profile.
Hypertriglyceridemia refers to a condition in which patients have high blood levels of triglycerides and is associated with increased risk of heart disease. It is one component of a range of lipid disorders collectively referred to as dyslipidemia. The overall dyslipidemia population in the U.S. is believed to be in excess of 100 million, with approximately 40 million of those diagnosed with hypertriglyceridemia (triglycerides greater than 200mg/dL) and an estimated 4 million with very high triglyceride levels (triglycerides greater than 500mg/dL). Very high triglycerides are associated with an increased risk of pancreatitis. Regulatory approval for the treatment of very high triglycerides is based on a significant reduction in the serum triglyceride levels.
About Omthera Pharmaceuticals, Inc.
Founded in 2008, Omthera Pharmaceuticals, Inc. is a privately held, specialty pharmaceutical company focusing its efforts on the clinical development of new therapies for dyslipidemia. Led by a team of experts with exceptional experience in developing new therapies for lipid disorders, Omthera is dedicated to developing innovative therapies for the millions of patients who have elevated triglyceride levels and increased risk of cardiovascular disease. Omthera holds worldwide rights to Epanova under a license from Chrysalis Pharma AG, a privately held Swiss company that is the owner of the product. For more information, please visit www.omthera.com
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