Drug Pipeline

Cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed for patients with arthritis and other conditions because of their lower risk for gastrointestinal adverse events compared with nonselective NSAIDs 1,2

Dapoxetine (Alza/Ortho-McNeil) is a novel oral medication undergoing FDA review for premature ejaculation, one of the most common disorders of sexual dysfunction in men. Dapoxetine is a fast-acting inhibitor of the serotonin reuptake transporter. It has a short half-life and is structurally related to the antidepressant fluoxetine, allowing for on-demand dosing.

Small artery elasticity improves more with coadministration of amlodipine and atorvastatin compared with either treatment alone, said Jay N. Cohn, MD, at the 20th annual meeting of the American Society of Hypertension (ASH) in San Francisco. The additive effect of amlodipine and atorvastatin on small artery compliance may explain the superior clinical cardiovascular outcomes associated with the combination versus monotherapy with either drug.

Kidney transplant recipients on an immunosuppressive regimen of sirolimus plus cyclosporine who had their cyclosporine withdrawn at an early stage had significantly better graft survival than patients who remained on cyclosporine. The advantage appeared to be related to significantly improved kidney function in the patients in whom cyclosporine was withdrawn, reported Graeme Russ, MD, at the American Transplant Congress 2005 in Seattle, Wash.

A study was conducted to determine the cost and patient adher- ence rates of lipid-lowering therapy with an extended-release niacin and lovastatin (ERNL) combination agent versus a separate extended-release niacin and statin (ERN-S) combination or statin monotherapy.

The objective of this study was to track the utilization of anti-inflammatory drugs among patients with active rofecoxib prescriptions at the time of market withdrawal through retrospective analysis of pharmacy records and to assess the need for COX-2 inhibitor therapy due to gastrointestinal risk factors.

Following the voluntary withdrawal of rofecoxib in September 2004 and the subsequent FDA-requested withdrawal of valdecoxib in April 2005, formulary decision-makers are considering options in navigating the changing pain management landscape. With one remaining COX-2 inhibitor available on the market (celecoxib [Celebrex, Pfizer]) and more cardiovascular (CV) risk data available for the class, the efficacy, adverse events, risk/benefit profiles, and costs of both COX-2-selective and nonselective NSAIDs are receiving more attention than ever.

Accelerated approval granted for protease inhibitor

First-in-class approved for type 2 diabetes

Mometasone topical solution 0.1% (equiv to Elocon topicallotion)

Broad spectrum antibiotic approved for cSSSIs and cIAIs

Post-operative ileus causes significant patient morbidity and is a major contributor to patient discomfort and increased length of hospitalization post-operatively. Alvimopan (Entereg, Adolor/GlaxoSmithKline), a peripherally selective opioid mu receptor antagonist with gastrointestinal (GI) tract-specific activity, is undergoing FDA review for the treatment of post-operative ileus.

Psoriasis is a chronic, inflammatory dermatologic disease that can have a significant physical and psychological impact on affected patients.

The new independent Drug Safety Oversight Board (DSB) within CDER will employ a two-pronged approach to create "a new culture of openness, improved oversight, and enhanced independence," according to FDA officials.

New regulations proposed by the California state Department of Managed Health Care (DMHC) that are expected to be implemented by the end of this year would require HMOs in California to cover all medically necessary prescription drugs, even if they are excluded from a plan's formulary.

The new independent Drug Safety Oversight Board (DSB) within CDER will employ a two-pronged approach to create "a new culture of openness, improved oversight, and enhanced independence," according to FDA officials.

The use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure (HF). However, the risk does not extend beyond the first year after diagnosis and does not appear to differ among the types of drug therapy, according to researchers who assessed 25,680 patients in the UK General Practice Research Database between 1988 and 1999. The researchers categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (OHA), and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin.

Analyses of 3 retrospective databases found that warfarin is much less effective at preventing strokes in the real world in patients with chronic atrial fibrillation (AF) than it is in clinical trials. The retrospective data were reported at the ASA's International Stroke Conference 2005.

Twice-daily ophthalmic NSAID approved to reduce inflammation after cataract surgery

Oral therapy approved for hepatitis B infection

Clopidogrel reduces 28-day mortality in the treatment of patients with acute myocardial infarction (MI) when given on top of standard therapies, but metoprolol has no effect on in-hospital mortality when given during the acute phase of MI.

An antihypertensive therapeutic strategy that starts with the calcium antagonist amlodipine is superior to one starting with the beta-blocker atenolol in preventing coronary heart disease (CHD) events, Peter S. Sever, MD, reported at the ACC Annual Scientific Session 2005.

The angiotensin receptor blocker (ARB) eprosartan is superior to the calcium antagonist nitrendipine in secondary stroke prophylaxis in patients with hypertension, Hans-Christian Diener, MD, reported at the ASA's International Stroke Conference 2005.

Ramelteon (Takeda Pharmaceuticals) is a selective melatonin receptor agonist awaiting FDA approval for the treatment of insomnia. Unlike the currently prescribed hypnotic agents that work by targeting gamma-aminobutyric acid (GABA) receptors, ramelteon offers a novel mechanism of action, specifically targeting the MT1 and MT2 receptors in the brain, which are thought to play a role in regulating sedation and circadian rhythms. Ramelteon is characterized by undergoing extensive first-pass metabolism along with having high oral bioavailability. Results of phase 2 clinical trials have demonstrated that ramelteon-treated patients had significantly shorter sleep onset latencies and longer total sleep times than placebo-treated patients. Furthermore, ramelteon therapy did not appear to impair patient cognition, memory recall, levels of alertness, or ability to concentrate. Data from animal studies suggest that ramelteon is not likely to cause abuse or physical dependence. Unlike the current FDA-approved..

Anti-sense compound (LR3001, Genta) for the treatment of chronic myelocytic leukemia

Combination indicated to reduce risk of stroke in hypertensive patients with LVH

First once-monthly therapy approved for treatment and prevention of osteoporosis

Among patients with a history of aspirin-induced ulcer bleeding, aspirin plus esomeprazole was shown to be superior to clopidogrel for the prevention of recurrent bleeding. The results of a 12-month, prospective, randomized, double-blind trial do not support current American College of Cardiology/American Heart Association guidelines recommending that clopidogrel be used as an alternative antiplatelet agent in patients who have a major gastrointestinal intolerance to aspirin, according to the authors of the study.

If approved, tipranavir (Boehringer Ingelheim) will be the ninth protease inhibitor (PI) available and the first nonpeptidic PI available in the United States. Designed by structure-based analysis, tipranavir is more flexible at the binding site, allowing for a potent and durable antiretroviral response. The tipranavir (TPV) and ritonavir (RTV) PI regimen (TPV/r) studied in clinical trials had a moderate pill burden, requiring 4 pills to be taken twice daily (2 RTV 100 mg and 2 TPV 250 mg).

Although oral antidiabetic medications initially may be effective for controlling hyperglycemia, these agents often fail to maintain adequate glycemic control as the disease progresses, and insulin eventually is required in most patients. This review explores strategies for identifying patients with type 2 diabetes who are failing to maintain glycemic control on oral agents and for transitioning these patients to insulin. Based on available data, patients are not reaching recommended glycemic goals due to delays in and reluctance towards intensification of therapy, resulting in an increased risk of complications.