Abbott said new data from two phase III studies show that in patients with multiple lipid problems, its ABT-335 combined with two commonly prescribed statins (atorvastatin and simvastatin), significantly improved three key lipids - LDL "bad" cholesterol, triglycerides and HDL "good" cholesterol - compared to the corresponding monotherapies. ABT-335, an investigational new fenofibric acid molecule, will be known as TriLipix.
Both TriLipix studies are part of the largest clinical program to date designed to evaluate the efficacy and safety of a fibrate in combination with statins. These studies using fenofibric acid combined with atorvastatin and simvastatin met their primary endpoints. Combination therapy significantly improved HDL and triglycerides compared to statin therapy alone, and significantly improved LDL compared to TriLipix alone. Both the combinations and the two statins had clinically meaningful reductions in LDL. In the clinical trials, combination therapy was generally well tolerated, with reported safety similar to the monotherapies. No rhabdomyolysis or unexpected liver, kidney or muscle safety signals were identified.
"With more than 30 million Americans taking lipid-altering therapies and only one quarter of them reaching treatment goals, there is a clear need for more data to support combination treatment options," said Christie Ballantyne, M.D., Methodist DeBakey Heart and Vascular Centre, Houston, and investigator in the TriLipix studies. "Data from these two studies show that TriLipix in combination with atorvastatin or simvastatin improved all three key lipids - LDL, HDL and triglycerides - in patients with multiple lipid problems."
Treatment guidelines endorsed by the National Cholesterol Education Panel (NCEP), the ACC and the American Heart Association have called for more aggressive management of lipids, including a lower LDL goal for many patients, as well as more aggressive management of HDL and triglycerides.
The two studies being presented at the ACC conference are part of a broad clinical programme to evaluate the efficacy and safety of TriLipix combined with statins. The efficacy and safety of TriLipix in combination with the three most commonly prescribed statins - rosuvastatin, atorvastatin and simvastatin - were evaluated in three randomized, multi-center, double-blind, controlled, 12-week Phase III studies, totalling 2,698 patients with mixed dyslipidemia. Patients included in the studies had multiple lipid problems, with an LDL greater than 130 mg/dL, triglycerides greater than 150 mg/dL and HDL less than 40 mg/dL for men and less than 50 mg/dL for women.
These studies, along with a 52-week long-term efficacy and safety open-label extension study of 1,911 patients, represent the largest program to date examining the efficacy and safety of a fibrate in combination with statins. More than 2,200 patients were treated with TriLipix in combination with statins across the four studies.
In the atorvastatin and simvastatin studies, presented at the ACC conference, 613 and 657 patients, respectively, were randomized to receive either TriLipix (135mg) combined with either 20mg or 40mg of the corresponding statin, TriLipix monotherapy (135mg) or statin monotherapy (20mg, 40mg or 80mg). The 80mg statin monotherapy arm was included in the study to assess safety and adverse events, but was not included in the statistical analysis.
The primary efficacy comparisons were mean per cent change in HDL and triglycerides in the combination versus a statin alone, and mean per cent change in LDL in the combination versus TriLipix alone. Both studies met all of their primary endpoints, with the combinations resulting in significant improvements over the pre-specified monotherapies for all three key lipids - LDL, triglycerides and HDL.
Additional data supporting TriLipix, including data from the Phase III trial evaluating TriLipix in combination with rosuvastatin in over 1,400 patients with mixed dyslipidemia, are planned for presentation at scientific forums throughout the year.
"Through our investment in a broad clinical development program for TriLipix, Abbott is providing physicians with data to help support a potential new treatment option for their patients," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott.
TriLipix is an investigational new fenofibric acid molecule, currently in clinical development for treating unhealthy lipid levels, including LDL cholesterol, triglycerides and HDL cholesterol. A New Drug Application for TriLipix for use as monotherapy and in combination with statins has been submitted to the US Food and Drug Administration.