Drug Pipeline

In a survey of trends in diabetes treatment from 1994 to 2007, investigators observed an increasing incidence of diabetes, a greater variety of drugs and combinations available for treatment, and a marked increase in the annual cost of diabetes medications.

On November 3, the US Supreme Court heard arguments in the case of Wyeth v Levine; the ultimate decision of the Court on this case may set a precedent on the issue of pre-emption, a tenet that FDA actions regarding drug approvals and medication safety supersede state laws.

As conflicts of interest between academia and the pharmaceutical industry are again under investigation, several pharmaceutical companies and universities are beginning to change their policies on disclosures and funding.

One month after Merck announced that the company was discontinuing development of taranabant, an investigational selective blocker of the cannabinoid-1 (CB-1) receptor that was being studied for the treatment of obesity, Sanofi-Aventis and Pfizer announced that they were also halting the development of their investigational CB-1 receptor antagonists (rimonabant and CP-945,598, respectively).

On November 7, 2008, a California Intermediate Appellate Court in San Francisco held that the "common-law duty [of Wyeth] to use due care in formulating its product warnings extends to patients whose doctors foreseeably rely on its product information when prescribing metoclopramide, whether the prescription is written for and/or filled with Reglan or its generic equivalent."

A phase 2/3 trial of atacicept in combination with mycophenolate mofetil and corticosteroids for the treatment of lupus nephritis in patients with systemic lupus erythematosus has been discontinued.

After spending 4 years laying a foundation that will streamline clinical testing and drug development, FDA leaders are poised to move the agency's Critical Path Initiative (CPI) from concept to implementation. Despite public concerns about drug safety, dangerous imports, and rising pharmaceutical costs, CPI has not fallen by the wayside.

A study published in the Journal of the American Medical Association reported that use of finasteride, a 5-alpha reductase inhibitor commonly used to treat benign prostatic hyperplasia (BPH), does not appear to be associated with an increased incidence of hip fractures in men; in fact, the agent appears to decrease the risk of hip fracture.

An observational retrospective study published in the American Journal of Respiratory and Critical Care Medicine demonstrated that mortality is reduced when patients with chronic obstructive pulmonary disease (COPD) are treated with cardioselective beta-blockers before major vascular surgery.

As a pharmacologic adjunct to stenting in patients with acute myocardial infarction (AMI), bivalirudin monotherapy outperformed the combination of a glycoprotein (GP) IIb/IIIa inhibitor and unfractionated heparin (UFH) over 1 year of follow-up, reported investigators at the 2008 Transcatheter Cardiovascular Therapeutics conference.

A phase 2 study published in the New England Journal of Medicine reported that alemtuzumab was more effective than interferon beta-1a in treating early, relapsing-remitting multiple sclerosis (MS), but the agent was also associated with higher rates of autoimmunity, including cases of immune thrombocytopenic purpura (ITP).

To effectively gauge the potential clinical and economic impact of drug and biologic therapies that are pending FDA approval, the monitoring of pharmaceutical pipelines has become an essential function of pharmacy benefit management (PBM) companies and managed care organizations (MCOs); one source of pharmaceutical pipeline information is subscription-based pharmaceutical pipeline databases. Examples of some of these databases, along with the types of information provided and advantages and disadvantages of such products, are presented.

This article reviews the 10 newly improved or investigational agents evaluated in this year's "Focus on" column and includes an update on the regulatory status of each drug.

Prasugrel is a thienopyridine prodrug under FDA review for the treatment of acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI). Clinical trials have demonstrated statistically significant inhibition of platelet aggregation with prasugrel relative to placebo and clopidogrel; however, this improved efficacy outcome entails a significantly increased rate of bleeding.

Generic drugs approved by FDA (through November 2008) including galantamine extended-release capsules and carbidopa/levodopa orally disintegrating tablets

FDA drug approvals

Merck has announced that they are discontinuing development of taranabant, an investigational selective blocker of the cannabinoid-1 (CB-1) receptor that was being studied for the treatment of obesity.

The Long-Term Intervention on Fractures with Tibolone (LIFT) study demonstrated a reduced risk of vertebral fracture, breast cancer, and possibly colon cancer but a significantly increased risk of stroke in older postmenopausal women treated with tibolone versus those treated with placebo.

FDA announced that the agency has posted on its website a report listing drugs that are being investigated for potential safety concerns.

Genentech informed healthcare professionals that a 70-year-old patient who has been treated with efalizumab (Raptiva) for chronic psoriasis for >4 years has developed progressive multifocal leukoencephalopathy (PML), a rare, progressive disease of the central nervous system that is usually fatal.

In the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, tiotropium therapy for patients with chronic obstructive pulmonary disease (COPD) was associated with long-term improvements in lung function, quality of life, and COPD exacerbations. The therapy did not, however, significantly reduce the rate of decline in forced expiratory volume in 1 second (FEV1) compared with placebo.

Even though the Medicare prescription drug benefit has provided access to medications at less-than-anticipated cost to the government-and lower out-of-pocket spending for seniors-many Democrats and consumer advocates want to overhaul the program. Critics contend that the federal government can negotiate prices with pharmaceutical companies that are lower than those obtained by private insurers operating prescription drug plans (PDPs), and some reformers charge that the program is too complex and confusing for elderly beneficiaries, pointing particularly to the infamous "donut hole" that is affecting more Medicare patients than anticipated.

A systematic search of the literature published in the International Journal of Clinical Practice demonstrated that angiotensin receptor blockers (ARBs) used as monotherapy or in combination with angiotensin-converting enzyme (ACE) inhibitors are not associated with a beneficial effect on mortality in patients with heart failure (HF).

A nested case-control analysis published in the Annals of Internal Medicine demonstrated an increased risk of all-cause and cardiovascular mortality among patients with recently diagnosed chronic obstructive pulmonary disease (COPD) treated with ipratropium.

Eltrombopag is a TPO receptor agonist that is currently pending FDA approval for the treatment of ITP. This agent has been granted orphan drug and priority review status. In May 2008, the Oncology Drugs Advisory Committee unanimously agreed that eltrombopag demonstrates a favorable risk:benefit profile for the short-term treatment of chronic ITP.

New biologic: Romiplostim (Nplate), a thrombopoietin mimetic peptibody, was approved on August 22, 2008, for the treatment of chronic ITP.

New molecular entity: Tetrabenazine (Xenazine), a monoamine depleter, was approved on August 15, 2008, for the treatment of chorea associated with Huntington's disease.

This article reviews the role of individual therapeutic agents and combination therapies that can be used for the treatment of mixed dyslipidemia.

The Comparative Effectiveness Research Act of 2008 would establish the Health Care Comparative Effectiveness Research Institute as a private, nonprofit, nongovernmental entity that would contract with government agencies and private research organizations to conduct systematic reviews, observational studies, and randomized controlled clinical trials to obtain evidence regarding the clinical effectiveness of therapies and treatments.

Primary androgen deprivation therapy (PADT), the second most common treatment for localized prostate cancer following prostatectomy, is no more effective than conservative medical management for prolonging survival in most older patients with prostate cancer.