Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

Trastuzumab emtansine: a review of its use in patients with HER2-positive advanced breast cancer previously treated with trastuzumab-based therapy.

Trastuzumab emtansine (Kadcyla™) is an antibody-drug conjugate consisting of the humanized anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab covalently linked to the highly potent microtubule inhibitory drug DM1 (a cytotoxic derivative of maytansine) via a stable thioether linker. Intravenous trastuzumab emtansine was recently approved for use in patients with HER2-positive, unresectable, locally advanced (in the EU) or metastatic (in the USA and EU) breast cancer who had previously received trastuzumab and a taxane (separately or in combination), making it the first antibody-drug conjugate approved in this indication. This article reviews the efficacy and tolerability of trastuzumab emtansine in these patients and summarizes its pharmacology. In the well-designed EMILIA study, trastuzumab emtansine significantly prolonged progression-free survival and overall survival, relative to treatment with lapatinib plus capecitabine, in patients with HER2-positive, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane. Trastuzumab emtansine was generally well tolerated in this study, with <6% of patients discontinuing treatment because of adverse events. Based on its efficacy and favourable tolerability, the US National Comprehensive Cancer Network guidelines recommend trastuzumab emtansine as the preferred option in patients with HER2-positive metastatic breast cancer who have received previous trastuzumab-based therapy.

Tasimelteon: first global approval.

Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder. It is the first US FDA-approved medication for this orphan indication. Melatonin is thought to play a role in governing the body's natural sleep-wake cycle through physiological processes regulated in the suprachiasmatic nucleus of the hypothalamus. The hormone is secreted by the pineal gland, with onset typically occurring when daylight begins to dim. In healthy, sighted individuals, the endogenous circadian period is a little over 24 hours, but is entrained to the 24-hour day through exposure to environmental cues, such as light and darkness. In the absence of these cues, synchronisation is lost and the circadian rhythm follows the intrinsic non-24-hour clock, resulting in disorders like non-24-hour sleep-wake disorder. Because the rhythm of endogenous melatonin is considered to be a measure of the human circadian phase, the carefully timed administration of melatonin analogues, such as tasimelteon, can potentially promote circadian readjustment. This article summarizes the milestones in the development of tasimelteon leading to this first approval for the treatment of non-24-hour sleep-wake disorder.

Naproxen/esomeprazole fixed-dose combination: for the treatment of arthritic symptoms and to reduce the risk of gastric ulcers.

Naproxen/esomeprazole is a fixed-dose combination of the NSAID naproxen and the proton pump inhibitor esomeprazole. In two well designed, 12-week studies, naproxen/esomeprazole fixed-dose combination was noninferior to celecoxib in treating the signs and symptoms of disease in patients with osteoarthritis of the knee, as assessed by the mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain and function scores and Patient Global Assessment scores (coprimary endpoints). Two other studies showed that the cumulative incidence of gastric ulcers (primary efficacy measure) was significantly lower with naproxen/esomeprazole than with enteric-coated naproxen alone during up to 6 months' therapy in patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or any other condition requiring daily NSAID therapy. The fixed-dose combination was generally well tolerated in these studies, with an upper gastrointestinal tolerability profile generally better than that of naproxen and similar to that of celecoxib.