Drug Pipeline

FDA's paperless e-labeling initiative will allow manufacturers to transmit labeling information electronically to prescribers, pharmacists, and patients.

Although the mechanism of action of imiquimod is unknown, an open-label study suggests that the drug may act by increasing the filtration of lymphocytes, dendritic cells, and macrophages into the tumor lesion. Imiquimod was approved on July 14, 2004, for an expanded indication to include the treatment of biopsy-confirmed, primary superficial basal cell carcinoma (sBCC) in immunocompetent adults.

A newly released update to the National Cholesterol Education Program's (NCEP) guidelines on cholesterol management recommend that clinicians consider more intensive treatment options for patients at high and moderately high risk for heart attack. These evidence-based recommendations include setting lower treatment goals for low-density lipoprotein cholesterol (LDL-C) and initiating cholesterol-lowering drug therapy at lower LDL thresholds.

This novel dyslipidemia therapy features a combination of 2 previously approved drugs: ezetimibe and simvastatin. Ezetimibe exerts its effect by selectively inhibiting intestinal cholesterol and related phytosterol absorption. This mechanism of action is complemented by that of simvastatin, which acts through inhibition of the HMG-CoA reductase enzyme. The ezetimibe/simvastatin combination was approved on July 23, 2004, for the treatment of hypercholesterolemia and mixed hyperlipidemia

Although warfarin is an effective drug in the treatment and prevention of thromboembolism, dosing complexities and drug interactions have led to its underutilization and a desire for an alternative agent. Ximelagatran (Exanta, AstraZeneca) is a novel oral anticoagulant that can be taken in standardized doses without the use of periodic blood monitoring to determine the level of anticoagulation. Large prospective clinical trials have shown ximelagatran to be similar in efficacy compared to the standard of therapy in the prevention and treatment of thromboembolism with similar or lower rates of bleed. Of concern, however, is the fact that that ximelagatran may elevate hepatic enzymes. An NDA was filed for ximelagatran on December 23, 2003, and FDA’s Cardiovascular and Renal Drugs Advisory Committee is scheduled to review the drug for the prevention of stroke and thromboembolism at a meeting on September 10, 2004. This article reviews ximelagatran’s chemistry and pharmacology, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage and administration.

The number of patients presenting with typical gastroesophageal reflux disease (GERD) symptoms and the prevalence of GERD symptoms in the general population make the prescription of proton-pump inhibitors (PPIs) by primary-care physicians commonplace. An active medication use evaluation (MUE) program that places symptom control as a primary concern can help rationalize PPI drug therapy and improve patient care. A treatment guideline that follows the current practice of empiric therapy, recommends periodic monitoring, and encourages further gastroesophageal evaluation (ie, endoscopy and pH monitoring) for assessing adequacy of treatment and treatment failures is a key component of a successful program.

Consumer-driven healthcare will greatly influence benefit and co-pay structures over the next decade, HealthTrans leaders predict.

Proposals to allow Medicare to negotiate prices similar to those available to the VA are unjustified, according to PhRMA.

Pioglitazone was also significantly superior to the other 2 treatment groups in decreasing triglycerides.

A recent study found that atorvastatin at its starting dosage reduces the risk of a first major cardiovascular event in patients with type 2 diabetes, said Helen Colhoun, MD, at the 64th scientific sessions of the American Diabetes Association (ADA) in Orlando.

Release of GLP-1 in responseto an ingested meal and glucose load plays a major role in the development of impaired insulin secretion.

At Digestive Disease Week in New Orleans, Steve Flamm, MD, associate professor of medicine and medical director of liver transplantation, Northwestern University, Chicago, Ill, presented study findings indicating that patients with chronic hepatitis C virus (HCV) infection and persistently normal liver enzymes derive as much benefit from pegylated interferon-alfa 2b plus ribavirin therapy as do patients with elevations in serum alanine aminotransferase (ALT). According to Dr Flamm, lead investigator for the study, "... a fraction of patients with normal liver enzymes do have aggressive liver disease on liver biopsy despite their liver tests being normal."

Amidst a national focus and heated debate over rising drug costs and price hikes, Abbott Laboratories quadrupled the price in December of its widely used protease inhibitor ritonavir (Norvir) from $1.71 to $8.57 for a 100 mg capsule.

Three months after the stroke, recovery was significantly higher among the patients who had been taking statins.

Rifaximin (Xifaxan, Salix), the first nonsystemic, gastrointestinal-selective oral antibiotic to receive approval for the treatment of travelers' diarrhea, is also an effective prophylaxis for travelers' diarrhea, according to data released at Digestive Disease Week in New Orleans.

Peginterferon alfa-2a monotherapy demonstrated superior end-of-follow-up response rates to peginterferon alfa-2 in combination with lamivudine.

A study was conducted to assess hospital admission rates for congestive heart failure in patients dispensed cyclooxygenase-2 (COX-2) inhibitors or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Researchers at the Institute for Clinical Evaluative Sciences in Toronto, Ontario, Canada, studied patients taking rofecoxib (Vioxx, Merck), celecoxib (Celebrex, Pfizer), and nonselective NSAIDs, with a control group consisting of non-NSAID users who were not given any study drugs. Study findings indicate that, relative to non-NSAID users, patients receiving rofecoxib and nonselective NSAIDs had an increased risk of admission for congestive heart failure than patients taking celecoxib.

Tumor necrosis factor (TNF) antagonists increase the risk of granulomatous infectious disease, including tuberculosis, according to a study-the largest of its kind to date-published in the journal Clinical Infectious Diseases. The risk of infection was 3.25-fold greater among patients who received infliximab (Remicade, Centocor) than among those who received etanercept (Enbrel, Wyeth/Amgen), the study found.

The parasympatholytic action of trospium reduces the tonus of smooth muscle in the bladder by antagonizing the effect of acetylcholine on muscarinic receptors. Trospium was approved on May 28, 2004, for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Medicare officials predict that beneficiaries will realize more substantial savings as sponsors drop their prices even more.

This nonsystemic, gastrointestinal-selective oral antibiotic exerts its effect by binding to the beta-subunit of bacterial DNA- dependent RNA polymerase. Rifaximin was approved on May 25, 2004, for the treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli in patients aged 12 years and older.

Common and serious comorbidities in chronic kidney disease include bone and mineral disorders, especially hyperphosphatemia and secondary hyperparathyroidism, and cardiovascular calcification and cardiovascular disease. Managing these complications typically requires the use of phosphate-binding compounds and vitamin D analogues. The selection and use of phosphate-binding agents in particular requires careful consideration of various factors such as calcium load and increased risk of subsequent cardiovascular calcification. Currently available calcium-containing phosphate binders have been demonstrated to contribute to patient calcium loads, and their use in hemodialysis patients has been associated with significant and progressive cardiovascular calcification. Thus, there is increasing interest in the use of calcium-free products, which can effectively bind phosphate without enhancing the risk for cardiovascular calcification.

The intravenous (IV) formulation of esomeprazole, the S-isomer of the proton pump inhibitor (PPI) omeprazole, is currently under FDA review for the short-term treatment of gastroesophageal reflux disease (GERD) as an alternative in patients unable to continue taking oral esomeprazole. Clinical studies have shown esomeprazole to be equivalent to the other currently available PPIs with respect to safety. The intravenous formulation, given either as a 30-minute infusion or 3-minute injection, has been found to be comparable to the oral dosage form based on pharmacokinetic and pharmacodynamic studies in healthy subjects. Limited studies suggest that IV esomeprazole 40 mg/d may provide a more effective antisecretory profile than either IV lansoprazole 30 mg/d or IV pantoprazole 40 mg/d. Data on clinical efficacy is limited to 1 abstract that reported no significant differences in healing rates in subjects with erosive esophagitis administered esomeprazole either 40 mg orally or IV daily. More clinical studies are needed to define its limited role as an alternative in those patients with acid-related disorders unable to tolerate the oral formulations.

More state governments and public health agencies that are facing funding cutbacks are looking for ways to obtain less expensive pharmaceuticals from Canada in order to reduce spending on pharmaceuticals. So far this year, 21 states have considered drug reimportation bills or resolutions, according to the National Conference of State Legislatures.

Acetaminophen use is associated with an increased rate of newly diagnosed adult-onset asthma, according to a study published in the American Journal of Respiratory and Critical Care Medicine. The study findings, from the Nurses Health Study, confirmed and extended the results of similar cross-sectional studies, although the authors stated that it would be premature to recommend the avoidance of acetaminophen for all adults with asthma.

More than half the women suffering from early-stage breast cancer (ESBC) are at increased risk of recurrence or death because of substantial reductions-planned or unplanned-in relative dose-intensity (RDI) when treated with adjuvant chemotherapy, according to a study published in the Journal of Clinical Oncology.

Combination use of clopidogrel and aspirin the night before undergoing carotid endarterectomy (CEA) may significantly reduce the risk of cerebral emboli, according to a study published in the journal Circulation.

Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, can help stop or delay the progress of white matter lesions (WML) in patients with prior cerebrovascular disease, according to research presented at the annual meeting of the American Academy of Neurology.

Adjusted-dose warfarin compared to aspirin more effectively reduces the high risk of secondary stroke in atrial fibrillation (AF) patients who have a history of transient ischemic attack (TIA), according to a study published in the journal Stroke.

It remains to be seen how these importation proposals could affect R&D and drug development over the long run.