Joanna Cosgrove09.15.11
Omthera Pharmaceuticals, Inc., a Bedminster, NJ-based privately-held, emerging specialty pharmaceuticals company, has begun enrollment for its Phase III clinical trial to determine the effects of its EPA/DHA compound called Epanova on patients with persistent hypertriglyceridemia despite statin therapy.
Epanova is Omthera’s ultra-pure mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and is currently in development as a “prescription omega 3 free fatty acid for the treatment of patients with very high triglycerides” (greater than or equal to 500 mg/dL).
Hypertriglyceridemia 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 more than 27 million of those diagnosed with hypertriglyceridemia (TGs greater than 200 mg/dL) and an estimated five million with very high triglyceride levels (TGs greater than 500 mg/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 serum triglyceride levels.
The randomized, double-blind, placebo-controlled, parallel group trial—called ESPRIT (short for Epanova combined with a Statin in Patients with HypertRiglycerIdemia to Reduce Non-HDL CholesTerol)—will span 6 weeks, and is designed to confirm if adding Epanova (2 grams or 4 grams daily) to existing statin monotherapy can beneficially impact the non-HDL cholesterol levels of those who are at high risk for cardiovascular disease. The secondary objectives of the trial are to evaluate the safety of the Epanova and statin combination therapies, and to evaluate the effects of the combination therapies on other lipids and lipoproteins.
The first of an expected 642 total subjects has already been enrolled for the trial, which will be conducted at approximately 100 sites across the U.S.
The trial was granted a Special Protocol Assessment (SPA) from FDA—an agreement between the company and the FDA indicating that the company’s proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support regulatory approval. Final marketing approval will depend upon efficacy results, adverse event profiles and an evaluation of the benefit/risk of a treatment as demonstrated in the trial.
Dr. Stephen Nicholls, assistant professor of Molecular Medicine and the cardiovascular director of the Cleveland Clinic Coordinating Center for Clinical Research and principal investigator for the ESPRIT study pointed out how the outcome of the clinical trial could beneficially impact millions of Americans currently on statin therapy who remain at risk for cardiovascular events. “Non-HDL-C is an important target of drug therapy for patients on a statin with TG between 200 and 500 mg/dL,” he said. “The results of this trial, if positive, could further support the use of omega 3 free fatty acids as a treatment for these patients.”
Dr. Michael Davidson, chief medical officer and co-founder of Omthera, echoed Dr. Nicholls’ optimism. “Data generated earlier this year demonstrated that Epanova has superior bioavailability compared to the market leader, Lovaza, and our EVOLVE trial, intended to support our planned NDA filing, has been actively enrolling subjects,” he said. “With the initiation of the ESPRIT trial, we have now taken a further step to potentially expand the indication to include patients with persistent hypertriglyceridemia and high risk for cardiovascular disease, who are on statin therapy, for which there are currently no approved prescription omega 3 drugs.”
The company pointed to a growing body of data supporting Epanova and noted its 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 greater than or equal to 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,” the company stated via press release.
In addition to the ESPRIT trial, Omthera is also involved in the ongoing Phase III EVOLVE (EpanoVa fOr Lowering Very high triglyceridEs) trial, which received SPA approval in November 2010, and will form the basis for filing a New Drug Application (“NDA”) with FDA. The company said the results of the ESPRIT trial are not required for regulatory approval, but rather, if positive, would serve to expand the use of Epanova to a larger patient population.
Epanova is Omthera’s ultra-pure mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and is currently in development as a “prescription omega 3 free fatty acid for the treatment of patients with very high triglycerides” (greater than or equal to 500 mg/dL).
Hypertriglyceridemia 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 more than 27 million of those diagnosed with hypertriglyceridemia (TGs greater than 200 mg/dL) and an estimated five million with very high triglyceride levels (TGs greater than 500 mg/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 serum triglyceride levels.
The randomized, double-blind, placebo-controlled, parallel group trial—called ESPRIT (short for Epanova combined with a Statin in Patients with HypertRiglycerIdemia to Reduce Non-HDL CholesTerol)—will span 6 weeks, and is designed to confirm if adding Epanova (2 grams or 4 grams daily) to existing statin monotherapy can beneficially impact the non-HDL cholesterol levels of those who are at high risk for cardiovascular disease. The secondary objectives of the trial are to evaluate the safety of the Epanova and statin combination therapies, and to evaluate the effects of the combination therapies on other lipids and lipoproteins.
The first of an expected 642 total subjects has already been enrolled for the trial, which will be conducted at approximately 100 sites across the U.S.
The trial was granted a Special Protocol Assessment (SPA) from FDA—an agreement between the company and the FDA indicating that the company’s proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support regulatory approval. Final marketing approval will depend upon efficacy results, adverse event profiles and an evaluation of the benefit/risk of a treatment as demonstrated in the trial.
Dr. Stephen Nicholls, assistant professor of Molecular Medicine and the cardiovascular director of the Cleveland Clinic Coordinating Center for Clinical Research and principal investigator for the ESPRIT study pointed out how the outcome of the clinical trial could beneficially impact millions of Americans currently on statin therapy who remain at risk for cardiovascular events. “Non-HDL-C is an important target of drug therapy for patients on a statin with TG between 200 and 500 mg/dL,” he said. “The results of this trial, if positive, could further support the use of omega 3 free fatty acids as a treatment for these patients.”
Dr. Michael Davidson, chief medical officer and co-founder of Omthera, echoed Dr. Nicholls’ optimism. “Data generated earlier this year demonstrated that Epanova has superior bioavailability compared to the market leader, Lovaza, and our EVOLVE trial, intended to support our planned NDA filing, has been actively enrolling subjects,” he said. “With the initiation of the ESPRIT trial, we have now taken a further step to potentially expand the indication to include patients with persistent hypertriglyceridemia and high risk for cardiovascular disease, who are on statin therapy, for which there are currently no approved prescription omega 3 drugs.”
The company pointed to a growing body of data supporting Epanova and noted its 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 greater than or equal to 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,” the company stated via press release.
In addition to the ESPRIT trial, Omthera is also involved in the ongoing Phase III EVOLVE (EpanoVa fOr Lowering Very high triglyceridEs) trial, which received SPA approval in November 2010, and will form the basis for filing a New Drug Application (“NDA”) with FDA. The company said the results of the ESPRIT trial are not required for regulatory approval, but rather, if positive, would serve to expand the use of Epanova to a larger patient population.
