Experimental Drug Shows Promise Against Cushing's Disease (3/7/2012)

Experimental Drug Shows Promise Against Cushing's Disease

In phase 3 trial, symptoms improved in people with rare hormonal disorder, study found.
WEDNESDAY, March 7 (HealthDay News) -- An experimental drug called pasireotide reduced levels of the "stress hormone" cortisol and improved symptoms in patients with Cushing's disease, a new study found.

Cushing's disease is a rare (three to five cases per million people) hormonal disorder that causes a wide range of health problems and, if untreated, significantly increases a patient's risk of dying at a much younger age than normal, researchers said in a news release.

Weight gain, high blood pressure, mood swings, irregular or absent menstrual periods, insulin resistance, glucose intolerance and type 2 diabetes are among the symptoms of Cushing's disease. It is a form of Cushing's syndrome, which is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol.

This phase 3 study of 162 patients in 18 countries found that treatment with pasireotide reduced cortisol secretion by an average of 50 percent and returned some patient's cortisol levels to normal.

A phase 3 study means that a drug is in the final stages of testing that drugs undergo before they can be approved for treatment of a specific disease.

The study, funded by Novartis Pharma, appears in the March 8 issue of the New England Journal of Medicine.

Dr. Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York City, is not associated with the study but is familiar with its findings.

Mezitis said the study showed that the experimental treatment "improved metabolic abnormalities and emotional difficulties. Therefore, pasireotide injections become an alternative to surgical resection of the pituitary ACTH-secreting tumor, and may be shown to work with the FDA-approved mifepristone, which blocks the action of cortisol at receptors in the body."

Elevated blood sugar (glucose) levels occurred in 73 percent of the patients who took the drug, a side effect that requires close attention, according to senior study author Dr. Beverly Biller, of Massachusetts General Hospital.

Cushing's patients already have difficulty processing glucose, she noted.

"Those patients who already were diabetic had the greatest increases in blood sugar, and those who were prediabetic were more likely to become diabetic than those who began with normal blood sugar," Biller said in the hospital news release. "So this is real and needs to be monitored carefully."

Mezitis agreed that careful patient monitoring is important. "Blood-sugar elevations are dose-dependent with pasireotide and will need to be managed as indicated for diabetes," he said.

Source: http://www.womenshealt.gov/new/news/headlines/662454.cfm/

Experimental Drug Offers Hope for Rare Bone Disease: Study (3/7/2012)

Experimental Drug Offers Hope for Rare Bone Disease: Study

Replaces missing enzyme in babies with severe hypophosphatasia.

By Serena GordonHealthDay Reporter
WEDNESDAY, March 7 (HealthDay News) -- A new therapy may be the first to offer hope for children born with a rare disease that affects bone development, sometimes so severely that babies die because they're missing a rib cage to protect their lungs.

The inherited disorder is called hypophosphatasia, and the new medication is asfotase alfa. It works by replacing an enzyme that's missing in those with hypophosphatasia. Enzymes are substances responsible for speeding up certain chemical reactions. In hypophosphatasia, the missing enzyme is necessary for proper bone growth and normal metabolism.

A small study of babies and children younger than 3 who had debilitating or life-threatening hypophosphatasia found that treatment with asfotase alfa strengthened bones and improved lung function. After 48 weeks of treatment, many could start bearing weight on their legs and some infants were even taking their first steps.

"We saw striking improvements in these patients with severe hypophosphatasia who received the enzyme replacement," said the study's lead author, Dr. Michael Whyte, medical-scientific director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospitals for Children in St. Louis. Whyte is also a professor at Washington University School of Medicine in St. Louis, which conducted the study jointly with Shriners and other institutions.

Results of the research are published in the March 8 issue of the New England Journal of Medicine.

Severe hypophosphatasia affects about 1 in 100,000 babies born in the United States, according to the National Library of Medicine. It's estimated that more people may have the disease, but in far milder forms. The severity of the disease can range from life-threatening to simply causing dental problems in adults, according to background information in the article.

The enzyme in hypophosphatasia that isn't available in sufficient quantity is called alkaline phosphatase. It's responsible for the mineralization of bones and teeth. Mineralization is the process that causes minerals like calcium and phosphorus to be deposited in developing bones and teeth, according to the National Library of Medicine. Without enough alkaline phosphatase, several other substances can build up and cause damage.

There are no approved medical treatments for hypophosphatasia, according to the study.

The current study involved 11 children. All were given an initial intravenous infusion of asfotase alfa, followed by shots of the medication three times a week.

Parents of one baby removed their child from the trial during the initial intravenous treatment. A second baby died from an unrelated infection after more than seven months of treatment.

The remaining nine children have received at least 18 months of treatment with asfotase alfa.

X-rays taken at the start of the study and at weeks 24 and 48 showed significant improvement in bone formation after treatment. In addition, the babies showed improvement in lung function, physical skills, and in the development of intelligence, according to the study.

The treatment was "very well tolerated," Whyte said. And, he added, there was no evidence that the children were developing resistance to the drug.

Treatment with asfotase alfa needs to be ongoing, and it's not yet clear if there are long-term side effects. Whyte and his colleagues are continuing to study the patients enrolled in this trial. He said that he believes children born with the severe or life-threatening form of the disease should be given this medication, even though it's still considered experimental. The reason, he said, is the severe form of this disease is "invariably lethal, usually soon after birth."

Dr. Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York City, said the research is promising and groundbreaking. "They're correcting an inborn error of metabolism and mimicking what the body does," he said. "It would be like making someone with type 1 diabetes start making insulin on their own, rather than just replacing it from the outside. I think this will serve as a model for other types of diseases."

But, he added, the current patients will need to be closely monitored as they grow, and that there is a need for further studies.

The study was funded by Shriners Hospitals and Enobia Pharma, which was acquired last month by Alexion Pharmaceuticals. Whyte was a consultant for Enobia Pharma, according to a Washington University news release.

Source: http://www.womenshealt.gov/new/news/headlines/662508.cfm/

Efforts to Improve Research on Kids' Drugs Paying Off: Report (2/29/2012)

Efforts to Improve Research on Kids' Drugs Paying Off: Report

But information still limited on long-term safety, efficacy, especially for infants.
WEDNESDAY, Feb. 29 (HealthDay News) -- Federal laws requiring medical companies to conduct pediatric drug studies have helped provide guidance on whether it's safe or effective for children to use certain medications, a new U.S. report finds.

The Institute of Medicine (IOM) report noted, however, that there's still not enough data on the use of drugs in newborns or the long-term effects of drugs on kids generally. The IOM, part of the National Academies, is an independent, nonprofit organization that provides advice to U.S. policymakers, health professionals, industry and the public.

Congress has attempted to increase the number of pediatric studies of medications with the passage of two laws: the Best Pharmaceuticals for Children Act, which offers companies financial incentives to conduct the studies; and the Pediatric Research Equity Act, which requires pediatric studies in specific situations.

In reviewing these laws, which are due for reauthorization this year, the IOM committee found that both laws have had a positive effect on the use of drugs in children. The committee noted, however, that the laws could be more effective if the U.S. Food and Drug Administration used its authority to require that drug makers undertake long-term follow-up studies after products have been approved for sale.

Long-term studies are especially important for young patients because children's bodies and minds are not fully developed and they could be taking medications for chronic conditions over the course of many years, the report stated. The IOM committee added that newborns are also more vulnerable to the side effects of medications.

The report, released Feb. 29, concluded that Congress and the FDA could step in to improve research in these areas and force drug manufacturers to conduct timely long-term studies on the risk of medications among children or face penalties. This may be necessary, the report authors suggested in a news release from the National Academy of Sciences, because conducting research on children is more difficult and often yields less lucrative results than studies involving adults.

Source: http://www.womenshealt.gov/new/news/headlines/662238.cfm/

Bipolar Drug May Spur Weight Gain, Thyroid Problems: Review (1/20/2012)

Bipolar Drug May Spur Weight Gain, Thyroid Problems: Review

Overall, lithium still 'treatment of choice' but docs urged to watch for and manage side effects.
THURSDAY, Jan. 19 (HealthDay News) -- A new medical review finds that lithium, a common treatment for bipolar disorder, can lead to weight gain and causes high rates of abnormalities in the thyroid and parathyroid glands.

But the researchers found few signs of a link to skin problems or hair loss, and a suspected connection to birth defects hasn't been proven, according to the report published in the Jan. 20 online edition of The Lancet.

Overall, the findings reaffirm lithium's role as "a treatment of choice for bipolar disorder," two doctors wrote in an accompanying editorial.

While lithium is less popular than it was in the 1970s and '80s as a treatment for bipolar disorder, it's probably the most effective available mood stabilizer, said Dr. Bryan Bruno, acting chairman of the department of psychiatry at Lenox Hill Hospital in New York City, who was not involved with the review but is familiar with the findings.

"It remains very beneficial, and it's still a first-line agent for bipolar disorder," Bruno said.

But lithium has a variety of possible side effects, noted the authors of the review, led by Dr. John Geddes of the University of Oxford, Warneford Hospital in Oxford, England. Their analysis included 385 studies.

The review found that lithium can cause weight gain, slightly hinder the kidneys' ability to concentrate urine, and cause increased activity of the thyroid and parathyroid glands.

Geddes and his colleagues suggest that doctors talk about the possible side effects with patients and add a blood calcium test to the testing regimen to check for possible hyperparathyroidism.

Bruno said the information about hyperparathyroidism is new, and added that he's likely to order the relevant test more often.

Dr. Michael Berk, a professor of psychiatry at Deakin University in Australia and a co-author of an accompanying commentary in the journal, said that lithium "is still widely used, but perhaps not as widely used as it should be."

Commenting on the review, he stated: "While lithium has potential side effects, these can be managed by understanding and anticipating them, in order to maximize the benefits and minimize the risks."

Source: http://www.womenshealth.gov/new//news/headlines/660880.cfm/