FDA Approves Novel Antiretroviral Drug

The U.S. Food and Drug Administration (FDA) today approved maraviroc, an antiretroviral drug for use in adult HIV patients. Maraviroc, sold under the trade name Selzentry, is the first in a new class of drugs designed to slow the advancement of HIV and received priority review by the FDA.

Maraviroc is approved for use in combination with other antiretroviral drugs for the treatment of adults with CCR5-tropic HIV-1, who have been treated with other HIV medications and who have evidence of elevated levels of HIV in their blood (viral load). Rather than fighting HIV inside white blood cells, maraviroc prevents the virus from entering uninfected cells by blocking the predominant route of entry, the CCR5 co-receptor. CCR5 is a protein on the surface of some types of immune cells. Among patients who have previously received HIV medications, approximately 50 percent to 60 percent have circulating CCR5-tropic HIV-1. "This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research.

The product label includes a boxed warning about liver toxicity (hepatoxicity) and a statement in the Warnings/Precautions section about the possibility of heart attacks. The FDA's approval of maraviroc is based on safety and effectiveness data from two double-blind, placebo-controlled studies. The 1,076 clinical trial participants were selected because they still showed evidence of HIV-1 in their blood, despite treatment with other HIV medications. A blood test for CCR5 tropic HIV-1 was used during clinical trials to identify patients appropriate for treatment with maraviroc.

FDA has received and is reviewing new safety data about Prilosec (omeprazole) and Nexium (esomeprazole).  On May 29, 2007, AstraZeneca, the manufacturer of Prilosec (omeprazole) and Nexium (esomeprazole), sent FDA and other regulatory authorities world-wide their preliminary review of new data from two small long-term clinical studies in patients with severe gastroesophageal reflux disease (GERD).  In both studies, patients were to be randomly assigned to receive treatment with a drug (either omeprazole or esomeprazole) or to have surgery to control their GERD.  The results from the study of Prilosec and analyses from an ongoing study of Nexium raised concerns that long-term use of Prilosec or Nexium may have increased the risk of heart attacks, heart failure, and heart-related sudden death in those patients taking either one of the drugs compared to patients who received surgery. 

Since May 29, the company has provided FDA with a large amount of additional data, including more information on patient follow-up from the two long-term studies mentioned above, and pooled analyses of other controlled clinical studies, including placebo-controlled trials of up to two-year's duration. At this time, FDA's preliminary conclusion is that collectively, these data do not suggest an increased risk of heart problems for patients treated with omeprazole or esomeprazole.  Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of these products at this time.

This early communication is in keeping with FDA's commitment to inform the public about its ongoing safety reviews of drugs.  FDA plans to complete its review within three months, and will communicate its conclusions and any resulting recommendations to the public at that time. 

Starting statin therapy as young as age 8 safely and effectively delays the early artery damage caused by familial hypercholesterolemia (FH), according to a Dutch study reported in the Aug. 7^th print issue of Circulation: Journal of the American Heart Association.

"Our data support early initiation of statin therapy in FH children, which might yield a larger benefit in the prevention of atherosclerosis later in life," said Barbara A. Hutten, Ph.D., senior author of the study.  "In our opinion, physicians should consider statin treatment for all FH children who are 8 or older."

FH leads to severely elevated levels of low-density lipoprotein (LDL) cholesterol, commonly called "bad cholesterol," beginning at birth.  The result is an early thickening of the artery walls, premature cardiovascular disease (5 percent by age 30; 50 percent by age 50), and an increased risk of early heart attack, Hutten said.

The disorder also interferes with normal artery functioning.  "Dilation is reduced in children with FH, which reflects an increased stiffness of the vessel wall.  This is the first sign of atherosclerosis," said Dr. Hutten, an assistant professor of clinical epidemiology at the University of Amsterdam's Academic Medical Centre in the Netherlands.

The incidence of dangerous hemorrhages connected to the use of these anticlotting agents was also much lower than had been feared, British researchers report.

"My interpretation of the finding is warfarin ought to be the treatment of choice for such people over the age of 75," said lead researcher Dr. Jonathan Mant, a reader in stroke epidemiology at the University of Birmingham.

His team presented its findings in the Aug. 11 issue of the journal The Lancet.

Researchers from the New England Research Institutes found that while men using statins did indeed have lower blood levels of androgens such as testosterone, it was more likely attributable to poor health rather than the use of statins. Their findings are published in the August issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

"The public health significance is that our study provides evidence that statins may not have a clinically meaningful impact on testosterone in the blood, although further studies should be done," said study author, Susan A. Hall, Ph.D., a research scientist at the New England Research Institutes. "That doesn't mean that statins may be lowering prostate cancer risk through one or more alternative pathways, but it doesn't appear to be working through reduction of male hormones.

Statins lower cholesterol and are commonly prescribed to treat and prevent heart disease. Since cholesterol is required for the production of male hormones researchers have theorized that statins may reduce production of these hormones. A large, recent study found that men using statin drugs were at lowered risk of developing metastatic or fatal prostate cancer, especially if the drugs were used over a long period of time. But other studies on statin use and prostate cancer risk have had mixed results, according to Hall.

A nationwide study led by researchers at UCSF provides evidence that inhaled nitric oxide is safe and effective for the prevention of the most common type of long-term lung disease of very premature infants.

"Chronic lung disease is a major source of morbidity in these infants. Neonatologists have been trying to figure out how to prevent it for years," said Philip Ballard, MD, PhD, lead study author and professor of pediatrics at UCSF. The benefit of inhaled nitric oxide for infants born close to term who suffer from the lung disease known as pulmonary hypertension has been known for some time, but the effect in preemies had not been clearly determined, according to Ballard.

Nitric oxide is a gaseous compound normally produced by the body, however, premature infants produce insufficient amounts. Recent clinical studies done elsewhere have found positive effects of inhaled nitric oxide in very premature infants, while some animal research has suggested that inhaled nitric oxide in preemies might interfere with the production of pulmonary surfactant, a substance critical to normal lung development and functioning.

The new study findings, reported in the August 2007 issue of "Pediatrics," found no adverse affects of inhaled nitric oxide on surfactant production or function, said Ballard, a neonatologist at UCSF Children's Hospital.