Drug Pipeline

Early statin use was associated with a lower risk of congestiveheart failure (CHF) development and in-hospital death in patientstreated for acute myocardial infarction (AMI), according to arecent observational study published in the International Journalof Cardiology.

The 55th Annual Scientific Session of the American College of Cardiology (ACC) assembled from March 11 to March 14, 2006, in Atlanta, Ga, to exchange new and continuing research in cardiovascular disease. The program featured more than 1,600 oral and poster presentations of original research and hundreds of invited lectures and interactive sessions, with many offering the opportunity to update attendees' knowledge of available and investigational pharmaceuticals.

Terconazole vaginal supposit-ories 80 mg (equiv to Terazol 3 vaginal suppositories)

This central nervous system stimulant delivered via a transdermal patch is the first and only non-oral therapy to receive approval for the treatment of attention deficit/hyperactivity disorder (ADHD).

While oral medications are the most common initial treatment of type 2 diabetes, oral monotherapy usually fails to control glucose levels over time. Findings have shown that after 3 years of monotherapy for type 2 diabetes, 50% of patients require combination therapy. After 9 years of monotherapy, that proportion rises to 75%. Nevertheless, even combination therapy eventually fails to control blood glucose levels in most patients. At this point, insulin therapy becomes necessary.

FDA officials said the agency "remains very concerned" that patients who take natalizumab (Tysabri, Biogen Idec/Elan) may develop a rare, potentially fatal brain infection called progressive multifocal leukoencephalopathy (PML). So starts a report from Reuters published on February 15, 2006. Should managed care also be concerned? If so, how should managed care formulary decision-makers respond? What is their role in managing patients who are clamoring for even more products to treat their diseases in an era in which it seems that miracles are a daily occurrence in the world of biotechnology? What role should managed care play in refereeing potentially devastating side effects for a disease that frightens patients as much as multiple sclerosis (MS)?

Last month FDA unveiled a long-awaited list of collaborative projects to streamline and accelerate the development of new medical treatments. Then Health and Human Services (HHS) Secretary Mike Leavitt joined Andrew von Eschenbach, MD, and Deputy Commissioner Janet Woodcock, MD, in urging implementation of the Critical Path initiative. Dr von Eschenbach, who hopes to oversee this effort as permanent FDA head following his official nomination to the position, says he is committed to fully implementing the initiative in order to "dramatically increase the success rate in moving products from the lab to the patient."

Aspirin is the cornerstone of therapy in the treatment and prevention of cardiovascular disease. The potential benefit of aspirin therapy may be significantly reduced in patients with aspirin resistance, creating a clinical and economic burden on the healthcare system. The purpose of this article is to clarify the term "aspirin resistance," describe the proposed mechanisms, review the clinical outcome studies with associated resistance testing, and discuss the potential pharmacologic management of this problem. Literature searches were performed using MEDLINE (January 1966 to January 2006) for review articles on aspirin resistance and antiplatelet activity. Aspirin's primary mechanism of action is to irreversibly inhibit cyclooxygenase-1 (COX-1); however, there are reports of alternative biochemical pathways producing platelet aggregation. The addition of thienopyridines to aspirin should be considered for the management of aspirin-resistant patients. (Formulary. 2006;41:192–201.)

In a post-hoc analysis, raloxifene (Evista, multiple manufacturers) appeared to attenuate stroke risk caused by high estradiol levels in postmenopausal women, said Jennifer S. Lee, MD, at the American Stroke Association's International Stroke Conference 2006 in Kissimmee, Fla.

An investigational free-radical trapping agent, NXY-059, significantly reduced disability when given within 6 hours of acute ischemic stroke, said Kennedy R. Lees, MD, at the American Stroke Association's International Stroke Conference 2006 in Kissimmee, Fla.

Withdrawing statins during the acute phase of ischemic stroke is associated with worse neurologic outcomes and larger brain injury compared with acute stroke patients who remain on their statins, said Florentino Nombela, MD, at the American Stroke Association's International Stroke Conference 2006 in Kissimmee, Fla.

An observational study of 51 outpatient practices found that about7 in 1,000 outpatients were administered a prescription thatviolated an FDA black box warning and that <1% of those patientshad an adverse drug event (ADE) as a result.

Cyclobenzaprine tablets 5 mg (equiv to Flexeril tablets)

Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) whose mechanism of action in the treatment of depression is not fully understood.

Cetuximab binds specifically to the epidermal growth factor receptor (EGFR), a transmembrane protein expressed in many human cancers, including those of the head and neck, colon, and rectum.

Type 2 diabetes mellitus is a progressive disease affecting more than 18 million Americans. Incretin mimetics and DPP-IV inhibitors are new classes of antihyperglycemic agents that may improve glycemic control in patients with type 2 diabetes. The incretin hormone, glucagon-like peptide 1 (GLP-1), stimulates glucose-dependent insulin secretion, suppresses inappropriate glucagon secretion, and slows gastric motility. GLP-1 levels are decreased in type 2 diabetes. GLP-1 is rapidly inactivated by the enzyme dipeptidyl peptidase-IV (DPP-IV), resulting in a half-life of <2 minutes. Strategies to increase GLP-1 activity include the development of incretin mimetics that are resistant to DPP-IV degradation and the development of DPP-IV inhibitors. Clinical trials have demonstrated that the incretin mimetics exenatide and liraglutide, as well as the DPP-IV inhibitor vildagliptin, improve glycemic control, reduce weight, and are fairly well tolerated. Exenatide (Byetta, Amylin/Lilly) was approved by FDA in April 2005..

Lubiprostone (Amitiza, Sucampo/Takeda) was approved on January 31, 2006, for the treatment of chronic idiopathic constipation in adults when the cause of the condition is unknown. The agent has a unique mechanism of action compared with current therapies on the market in that it locally activates specific chloride channels (ClC-2) in the lining of the small intestines after oral administration, thereby increasing intestinal fluids and softening bowel movements. In double-blind, placebo-controlled trials, lubiprostone demonstrated efficacy in improving the frequency of spontaneous bowel movements and other related constipation symptoms. Lubiprostone was reported to be well tolerated in clinical trials; the most common adverse effects were mild-to-moderate nausea and headache.

FDA began 2006 by unveiling a long-anticipated final rule that significantly overhauls approved labeling for drugs and biologics. This new rule has been in the works for years, delayed by manufacturer concerns that the revisions will expose companies to more liability suits. Although the new labeling's basic framework came as no surprise, compliance will require significant investments by manufacturers to meet the new design and content requirements, which will double the length of many package inserts (PIs).

A single day of famciclovir started within 6 hours of a genital herpes outbreak shortens the duration of recurrent genital herpes lesions, said Fred Y. Aoki, MD, at the 45th ICAAC meeting in Washington, DC.

Vancomycin may be overused for the treatment of hospital-acquired pneumonia, perhaps because of physicians' perceptions that patients are at high risk for methicillin-resistant Staphylococcus aureus (MRSA), according to a study by Robert H. Eng, MD, and colleagues at the Veterans Affairs New Jersey Health Care System in East Orange, NJ. The study was presented at the 45th ICAAC meeting in Washington, DC.

The use of acid-suppressive drugs, particularly proton pump inhibitors (PPIs), was associated with an increase in the risk of community-acquired Clostridium difficile-associated disease (CDAD) in the United Kingdom, reported Sandra Dial, MD, MSc, at the 45th ICAAC meeting in Washington, DC.

A study analyzing pharmacy claims among patients who receive chronic medications via 3-tier prescription drug plans found that patients who were prescribed generic or preferred medications by their physicians were the most likely to adhere with their treatments.

A study of 155 patients examining the effects of statins on patients diagnosed with acute coronary syndrome (ACS) suggests that statin therapy may increase survival rates and potentially extends the results of larger, recently performed randomized trials to those with low-density lipoprotein cholesterol (LDL-C) levels of 80 mg/dL and below.

Rheumatoid arthritis patients, hindered by an inadequate response to tumor necrosis factor-alpha (TNF-alpha) inhibitors, may find some relief in the form of a drug that belongs to a new class of selective costimulation modulators.

A prospective, double-blind, randomized, controlled trial comparing the effectiveness of levofloxacin and moxifloxacin in treating community-acquired pneumonia (CAP) among 394 hospitalized elderly patients (aged 65 years and older) demonstrated that moxifloxacin resulted in faster recovery than levofloxacin.

Topiramate safely decreases body mass, hypertension. Topiramate reduces body weight and blood pressure with generally mild-to-moderate adverse effects, according to a randomized, placebo-controlled trial involving obese subjects with hypertension.

A recent meta-analysis published in the Journal of the American Medical Association (JAMA) found that statins have no effect on cancer risk. The finding is in contrast with at least 7 retrospective analyses that suggest that statins reduce the risk of developing cancer.

Two recent studies in The New England Journal of Medicine (NEJM) focused on the breast cancer drug trastuzumab, a recombinant monoclonal antibody (Herceptin, Genentech/Roche).

Tight glucose control for a mean period of 6.5 years produces long-lasting cardiovascular benefits in patients with type 1 diabetes, according to a study published in the New England Journal of Medicine (NEJM).

FDA officials are reviewing an unexpected recommendation from the agency's Drug Safety and Risk Management Advisory Committee to add black box warnings to attention deficit/hyperactivity disorder (ADHD) stimulant medications. In addition to advising the agency about clinical trial designs that could better assess cardiovascular risks associated with ADHD therapies, members of the advisory committee called for immediate action to caution prescribers and patients about potential adverse events associated with these drugs. Concerns about increased risk of myocardial infarction, stroke, and sudden death have emerged with increased prescribing of stimulant ADHD drugs for adults and children?an estimated 4 million patients use these mediations, including more than 1 million adults.