Drug Pipeline

In the large cohort study referred to as the "The Million Women Study," the use of hormone replacement therapy (HRT) in postmenopausal women was demonstrated to increase the risk of ovarian cancer and death from ovarian cancer by 20% and 23%, respectively, compared to nonuse of HRT.

Briefs of FDA actions related to medication safety and reliability

In a large cohort study, it was demonstrated that the use of intravenous (IV) bisphosphonates was associated with an increased risk of inflammatory conditions or osteomyelitis of the jaw and the need for jaw or facial bone surgery.

Briefs of FDA actions/approvals of drugs, doses, and indications

First-time generic approvals: fosphenytoin for injection; pantoprazole delayed-release tablets; cefotetan for injection; cefepime for injection.

The latest FDA action (through September 2007) related to satraplatin, ropinirole (Requip CR), sumatriptan/naproxen (Trexima,) desvenlafaxine (Pristiq), eprodisate (Kiacta,) raloxifene (Evista), natalizumab (Tysabri), bifeprunox, fluticasone/salmeterol inhalation powder (Advair Diskus 500/50), LX211, TZP-101, Alferminogene tadenovec, Ad5FGF-4 (Generx), tramiprosate (Alzhemed), rilonacept, aripiprazole (Abilify), sapropterin (Kuvan), oral topotecan (Hycamtin), mifepristone (Corlux), vitiligo-derived IgG (VitiGam)

A new formulation for rivastigmine; a transdermal formulation of cholinesterase inhibitor approved for the treatment of mild-to-moderate dementia of the AD type and mild-to-moderate dementia associated with PD.

A new formulation for immune globulin intravenous (human), 10% liquid, a polyvalent human immunoglobulin G approved for the treatment of primary immunodeficiency and chronic immune thrombocytopenic purpura.

FDA has approved a new molecular entity for for use in combination with other antiretroviral agents for the treatment of adults with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

Data from 2 identical double-blind phase 3 studies demonstrated that patients with migraine who were assigned to sumatriptan plus naproxen were more likely to be pain-free at 2 hours and more likely to experience relief from both traditional and nontraditional migraine symptoms compared with those assigned to placebo.

Nebivolol, an investigational (NDA submitted) vasodilating beta-blocker, demonstrated a neutral effect on blood glucose levels in two 12-week clinical studies of patients with hypertension.

Investigators have demonstrated that patients with type 2 diabetes who use inhaled insulin as part of their basalbolus insulin regimen experience a small decline in pulmonary function.

An open-label extension study of exenatide demonstrated sustained blood glucose control and weight loss in patients with type 2 diabetes.

A quick-release formulation of bromocriptine reduces the incidence of diabetic cardiovascular complications in patients with type 2 diabetes and improves glycemic control in those patients who did not achieve HbA1c <7.5% with metformin plus a sulfonylurea.

An FDA advisory panel voted nearly unanimously to recommend that rosiglitazone (Avandia, GlaxoSmithKline) should remain on the market despite being in overwhelming agreement that the drug increases the risk of ischemic heart disease.

As Congress continues to work towards the reauthorization of the Prescription Drug User Fee Act (PDUFA), drug safety is once again at center stage after reports of serious cardiovascular problems associated with GlaxoSmithKline's diabetes drug rosiglitazone (Avandia).

Statins and fibrates reduce the risk of peripheral neuropathy in patients with type 2 diabetes independent of the agents' effects on lipids, according to results presented at the 67th annual scientific sessions of the American Diabetes Association.

The use of pioglitazone in patients with renal dysfunction, type 2 diabetes, and macrovascular disease can reduce the risk of death, nonfatal myocardial infarction (MI), and stroke according to results presented at the 67th annual scientific sessions of the American Diabetes Association.

Rosiglitazone did not demonstrate an increased risk of hospitalizations and death from cardiovascular causes (the composite end point) in an interim analysis of a prospective study.

A pooled analysis involving 1,748 patients in 4 randomized trials contradicts the results of recent trials that have demonstrated that the risks for death and myocardial infarction (MI) are potentially higher in patients receiving drug-eluting stents (particularlysirolimus-eluting stents) compared with patients receiving bare-metal stents.

In a small, retrospective, case-control study, it was demonstrated that aspirin (ASA) improved 7-day survival in patients with cancer who developed acute coronary syndrome (ACS), with or without thrombocytopenia.

The results of the Standard and New Antiepileptic Drugs (SANAD) trial, an unblinded, randomized, controlled, 2-arm study comparing the efficacy of various epilepsy drugs showed that for treatment of patients with partial seizures, lamotrigine demonstrated superior efficacy.

A greater percentage of patients at high risk for cardiovascular disease are likely to reach target low-density lipoprotein cholesterol (LDL-C) levels with initial treatment with rosuvastatin than with atorvastatin or simvastatin, according to the results of the Satisfying Optimal LDL-C ATP III Goals with Rosuvastatin (SOLAR) trial.

In a multicenter, randomized, double-blind, controlled trial, investigators demonstrated that in patients whose asthma was well controlled with the use of fluticasone twice daily, switching to fluticasone plus salmeterol once daily did not increase the rates of treatment failure, but switching to montelukast once daily resulted in a 60% increased risk of treatment failure.

In a 6-month, randomized, double-blind study, use of budesonide/formoterol as both maintenance and reliever therapy was demonstrated to provide better asthma control than either salmeterol/fluticasone plus terbutaline as needed or a fixed maintenance dose of budesonide/formoterol plus terbutaline as needed.

Use of naproxen or celecoxib does not prevent Alzheimer's disease (AD), at least within the early years after treatment initiation, according to a randomized, placebo-controlled, multicenter study.

Three-year results of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial show that a single, annual intravenous infusion of zoledronic acid can decrease risk of vertebral fracture by 70% and the risk of hip fracture by 41% among women with osteoporosis.

Atrial fibrillation (AF) is a disorder that affects >2 million people in the United States. Firstline antiarrhythmic agents (per American College of Cardiology/American Heart Association/European Society of Cardiology guidelines) that are currently used to treat recent-onset AF work by indiscriminately blocking various ionic channels, thereby inducing a prolonged ventricular action potential duration or possibly inducing ventricular arrhythmias in the presence of myocardial ischemia because of excessive conduction slowing in diseased cardiac tissue. Vernakalant is an atrial-selective, potassium and sodium-channel-blocking agent awaiting FDA approval for the indication of conversion of recent-onset AF to normal sinus rhythm.

Andrew von Eschenbach, MD, has faced a number of tough issues since he was sworn in as FDA's commissioner in December 2006, not the least of which is drug safety. Fewer new drugs have been coming to market, and pressure continues to mount for FDA to do more with limited resources. Legislation to reauthorize user fees for pharmaceutical and medical device manufacturers has to be approved by Congress by September 30, 2007, or FDA will have to lay off hundreds of staff members. The need for speedy legislative action has focused public attention on agency operations and policies, a trend likely to continue as the nation's healthcare system and prescription drug costs become a central issue in next year's presidential elections.

Briefs of FDA actions related to medication safety and reliability (ie, boxed warnings, dear healthcare provider letters)