Furiex Pharmaceuticals, Inc. (NASDAQ: FURX) today confirmed that Takeda Pharmaceutical Company Limited (Takeda) announced top line results of the EXAMINE ( EXamination of C Ardiovascular Outco Mes: Aloglipt IN vs. Standard of Car E in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) cardiovascular (CV) safety outcomes trial showing the primary endpoint of non-inferiority compared to placebo in addition to standard of care was met with no increase in CV risk in a Type 2 diabetes patient population at high-risk for cardiovascular events. These data, published in the New England Journal of Medicine ( NEJM) and also presented at the ESC 2013 Congress, demonstrate that alogliptin does not increase CV risk in Type 2 diabetes patients at high risk for major adverse cardiac events (MACE) due to a recent acute coronary syndrome (ACS). The trial’s primary objective was to evaluate non-inferiority with respect to CV risk based on a primary composite endpoint of CV death, nonfatal myocardial infarction and nonfatal stroke. The primary endpoint occurred at similar rates in the alogliptin and placebo groups (11.3% vs. 11.8% during a median follow-up period of 18 months; hazard ratio, 0.96; one sided repeated confidence interval bound, 1.16). “The EXAMINE trial is an important evaluation as it assesses cardiovascular safety in patients known to be at high risk for cardiovascular disease,” said June Almenoff, M.D., Ph.D., president and chief medical officer of Furiex. “Cardiovascular disease is very common in patients with Type 2 diabetes and the results of this study provide clinicians with assurance that alogliptin is effective and well-tolerated in these patients, and does not adversely affect cardiovascular health outcomes.” EXAMINE was a large, randomized, double-blind, placebo-controlled global clinical trial, designed to evaluate CV safety following treatment with alogliptin in addition to standard of care, versus placebo in addition to standard of care alone, in patients with type 2 diabetes and a recent ACS. During the trial, patients were randomly assigned to receive alogliptin or placebo in addition to standard of care medications for diabetes and CVD. A total of 5,380 patients were randomly assigned and followed for a median of 18 months and up to 40 months. The rate of premature discontinuation of the study drug was similar in the alogliptin and placebo groups. Patients also received high levels of standard of care for treatment of Type 2 diabetes and CV risk factors.
“We are pleased to see the results from the EXAMINE study,” added Fred Eshelman, PharmD., chairman of Furiex, “the trial provides key insights to clinicians treating diabetes patients and reinforces Takeda’s ongoing commitment to the diabetes community.”The principal secondary safety endpoint was the primary composite with the addition of hospitalization for unstable angina that required coronary revascularization within 24 hours of hospital admission. Testing of the secondary composite endpoint showed no difference in rates on alogliptin versus placebo (12.7% vs. 13.4%, hazard ratio, 0.95, one-sided repeated CI bound, 1.14). Other secondary endpoints included cardiovascular death alone and death from any cause. Cardiovascular death, occurred in 112 patients treated with alogliptin (4.1%) and 130 patients treated with placebo (4.9%) for a hazard ratio of 0.85 (95% confidence limits of 0.66 to 1.10, p = 0.21). Death from any cause occurred in 153 patients treated with alogliptin (5.7%) and 173 patients treated with placebo (6.5%) for a hazard ratio of 0.88 (95% confidence limits of 0.71 to 1.09, p = 0.23). Overall, rates of death from any cause and cardiovascular death were not statistically significant different between alogliptin and placebo groups. Additional safety end points included angioedema, hypoglycemia, pancreatitis, malignancy and results of laboratory testing. Rates of hypoglycemia, malignancy, pancreatitis, dialysis and serum aminotransferase elevations were similar for alogliptin and placebo groups. No events of pancreatic cancer were reported during the trial. The alogliptin and placebo groups also did not differ significantly with regard to rates of serious adverse events (33.6% and 35.5%, respectively, p = 0.14) About EXAMINE EXAMINE was a large, randomized, double-blind, placebo-controlled global clinical trial designed to evaluate CV safety following treatment with alogliptin in addition to standard of care, versus placebo in addition to standard of care alone, in patients with type 2 diabetes and a recent ACS (within 15 to 90 days prior to randomization). The trial had primary endpoint of non-inferiority with a composite of CV death, nonfatal myocardial infarction and nonfatal stroke.
In the alogliptin group, 71.4% of patients received 25 mg, 25.7% received 12.5 mg, and 2.9% received 6.25 mg daily. Alogliptin doses were adjusted according to renal function: estimated glomerular filtration rate (eGFR) by the Modification in Diet in Renal Disease formula ≥ 60 ml/min, 25 mg daily; < 60 ml/min but ≥ 30 ml/min, 12.5 mg daily; and < 30 ml/min, 6.25 mg daily. Premature discontinuation of the study drug was similar in the alogliptin and placebo groups (20.9% of patients versus 22.6%). The median duration of exposure to study drug was 533 days (interquartile range, 280 to 751 days). By the end of the study, the mean change from baseline in HbA1c was -0.33% and 0.03% in the alogliptin and placebo groups, and the least square means difference in HbA1c between alogliptin and placebo was -0.36% (95% CI, -0.43, -0.28, p < 0.001). In the analysis of the components of the primary end point, the hazard ratios were consistent with the overall result. Hazard ratios for death from any cause and cardiovascular death were consistent with the primary composite end point.About Type 2 Diabetes Type 2 diabetes is the most common form of diabetes and has reached epidemic proportions globally. The global health care expenditures to treat and prevent diabetes and its complications were estimated at $471 billion in 2012. By 2030, this number is projected to exceed $595 billion. In addition to diet and exercise, patients often need to take multiple medications to help manage blood glucose. Due to the chronic nature of this disease, combination therapy is often required to maintain diabetic control over many years of therapy. About Alogliptin Alogliptin is a dipeptidyl peptidase-4 inhibitor for the treatment of Type 2 diabetes in adults as an adjunct to diet and exercise. DPP-4 inhibitors are designed to slow the inactivation of incretin hormones GLP-1 and GIP. As a result, an increased amount of active incretins enables the pancreas to secrete insulin in a glucose-dependent manner, thereby assisting in the management of blood glucose levels. A New Drug Application (NDA) for NESINA® (alogliptin) was approved in April 2010 by the Japanese Ministry of Health, Labour and Welfare for the treatment of Type 2 diabetes, and the therapy is available under the same brand name in Japan. In July 2011 the fixed-dose combination LIOVEL® (alogliptin and pioglitazone) was approved by the Japanese Ministry of Health, Labor and Welfare. NESINA (alogliptin) was approved by the U.S. Food and Drug Administration as a monotherapy and also in fixed-dose combination with pioglitazone (OSENI®) and metformin HCl (KAZANO®) in January 2013 for the treatment of Type 2 diabetes in adults as adjuncts to diet and exercise. On July 26, 2013, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion for VIPIDIA™ (alogliptin) and Fixed-Dose Combinations VIPDOMET™ (alogliptin and metformin) and INCRESYNC™ (alogliptin and pioglitazone).
About FuriexFuriex Pharmaceuticals is a drug development collaboration company that uses innovative clinical development design to accelerate and increase value of drug development programs by advancing them through the drug discovery and development process in a cost-efficient manner. Our drug development programs are designed and driven by a core team with extensive drug development experience. The company collaborates with pharmaceutical and biotechnology companies and has a diversified product portfolio and pipeline with multiple therapeutic candidates, including one Phase III-ready asset, two compounds in Phase III development, one of which is with a partner, and four products on the market. The company’s mission is to develop innovative medicines faster and at a lower cost, thereby improving profitability and accelerating time to market while providing life-improving therapies for patients. For more information, visit www.furiex.com. Except for historical information, all of the statements, expectations and assumptions contained in this news release are forward-looking statements that involve a number of risks and uncertainties. Although Furiex attempts to be accurate in making these forward-looking statements, it is possible that future circumstances might differ from the assumptions on which such statements are based. In addition, other important factors which could cause actual results to differ materially include the following: the market acceptance of and demand for our partner’s marketed alogliptin products; the progress of the alogliptin products in commercialization as it relates to receiving future milestone and royalty payments; our continuing losses and potential need for additional capital; failure of our partner to successfully obtain regulatory approval to market and sell its alogliptin products in countries where these products are not yet approved; time required to gain regulatory approvals in individual countries where alogliptin products are not yet approved; the risks and expense of continuing the research and development activities of alogliptin products; and the other risk factors set forth from time to time in the SEC filings for Furiex, copies of which can be found on our website.