Par Pharmaceutical Companies Inc. announced that it has entered into an exclusive U.S. supply and distribution agreement with AstraZeneca to distribute the authorized generic version of AstraZeneca's Atacand(R) (candesartan cilexetil). Par has begun shipping 4 mg, 8 mg, 16 mg and 32 mg strengths of candesartan cilexetil tablets. According to IMS Health data, annual U.S. sales of Atacand(R) are approximately $113 million. Candesartan cilexetil is an angiotensin II receptor blocker indicated for the treatment of hypertension in adults and children 1 to < 17 years of age and the treatment of heart failure (NYHA class II-IV). Candesartan cilexetil reduces cardiovascular death and heart failure hospitalization. Candesartan cilexetil is contraindicated in patients who are hypersensitive to any component of the product. A black box warning is associated with this product regarding fetal toxicity. When pregnancy is detected, candesartan cilexetil should be discontinued as soon as possible. Drugs that act directly on the rennin-angiotensin system can cause injury and death to the developing fetus. Refer to full prescribing information for complete boxed warnings.

AstraZeneca presented the results of two pivotal Phase III studies of naloxegol showing the 25 mg dose of the investigational drug met its primary and secondary endpoints for efficacy and showed a safety profile consistent with previous studies. Data was presented at the Digestive Disease Week meeting in Orlando, Florida. Naloxegol is a peripherally-acting mu-opioid receptor antagonist, which has been specifically designed for the treatment of opioid-induced constipation a common and often debilitating side effect of prescription opioid pain medicines. The Phase III studies, KODIAC-04 and -05, were 12-week, multicenter, randomized, double blind, placebo-controlled pivotal trials that evaluated 12.5 mg and 25 mg doses of naloxegol, administered once-daily. The primary endpoint in both trials was percentage of OIC responders, versus placebo, over 12 weeks of treatment. The secondary endpoints included the 12-week response rate in a laxative inadequate response population, the median time to first spontaneous bowel movement and the number of days per-week with at least one bowel movement. Plans for naloxegol will be finalized over the coming months, incorporating the outcome of ongoing discussions with health authorities in the US, EU and Canada.

Bristol-Myers Squibb Company and AstraZeneca PLC announced the results from a 12-month sub-group analysis of a National Institutes of Health (NIH), open-label, long-term research study of metreleptin, an investigational agent for the treatment of metabolic disorders associated with inherited or acquired lipodystrophy (LD), a rare disease estimated to affect a few thousand people around the world, often with an early age of onset. In this analysis, which involved 39 pediatric LD patients less than 18 years of age at the time of study enrollment, investigational metreleptin treatment led to mean reductions in HbA1c (average blood sugar levels over three months) and triglyceride levels, as well as mean reductions in liver function tests (including alanine aminotransferase, or ALT, and aspartate aminotransferase, or AST). The full study was initiated in 2000 by investigators at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH, and is currently ongoing. Results from the pediatric analysis were presented at the 2013 Pediatric Endocrine Society (PES) Annual Meeting, being held in conjunction with the 2013 Pediatric Academic Societies (PAS) Annual Meeting in Washington, D.C. The analysis was conducted to examine the effects of investigational metreleptin on select metabolic parameters associated with LD, including HbA1c, triglyceride levels and liver function tests, in pediatric patients enrolled in the NIH study. The four major subtypes of LD -- congenital generalized LD, acquired generalized LD, familial partial LD and acquired partial LD were represented. Patients were stratified to one of two groups: children (<=12 years) or adolescents (>12 to <18), and data were analyzed at month 12 of metreleptin treatment, where available (n=27). In adolescents with LD, metreleptin treatment resulted in statistically significant reductions in elevated HbA1c (mean HbA1c decreased from 9.8+/-1.8% at baseline to 7.7+/-1.7% at month 12, for a mean decrease of 2.3+/-0.4%) and elevated triglycerides (mean triglyceride concentrations decreased from 1378+/-2024 mg/dL at baseline to 385+/-446 mg/dL at month 12, for a mean decrease of 44+/-14%). Elevated liver function tests also decreased (mean ALT decreased from 105+/-97 U/L at baseline to 59+/-108 U/L at month 12, for a mean decrease of 46+/-40%, and mean AST decreased from 87+/-89 U/L at baseline to 57+/-118 U/L at month 12, for a mean decrease of 31+/-38%). In younger children with LD, confirmed diabetes and hypertriglyceridemia were uncommon; however, mean liver function tests were markedly elevated at baseline and decreased with investigational metreleptin treatment (mean ALT decreased from 193+/-202 U/L at baseline to 155+/-274 U/L at month 12, for a mean decrease of 38+/-47%, and AST decreased from 119+/-112 U/L at baseline to 90+/-144 U/L at month 12, for a mean decrease of 30+/-29%). Reductions in ALT and AST did not reach statistical significance due to the small sample size and limited statistical power, but were clinically meaningful.