This past week, FDA announced (click here) the approval of ARCALYST™ (rilonacept, Regeneron Pharmaceuticals) for the treatment of rare inflammatory syndromes. In addition, Ferring Pharmaceuticals announced that it has submitted applications in Europe and the United States for the marketing authorization of its prostate cancer treatment, degarelix, a new GnRH receptor blocker intended for patients in whom androgen deprivation is warranted.

We are very pleased to announce that Target e*CRF® was used for the clinical trials for both submissions. There are now 14 products (NDA-2; PMA-10; BLA-1; and 510k-1) with FDA marketing approval that used Target e*CRF® for their pivotal trials. All of these studies passed FDA pre-approval inspection audits. Currently there is one NDA and one PMA in review.

For more information, please contact Dr. Jules T. Mitchel or Joyce Hays. For new business opportunities, contact Dr. Jules T. Mitchel

1. Did we learn a lesson from Avandia?

The FDA is supposed to allow drugs on the market only if they are safe and effective. In 2007, rosiglitazone (Avandia), became the latest medication found to have serious side effects that weren’t apparent when it was approved.

Like insulin and other diabetes drugs, rosiglitazone and a similar drug, pioglitazone (Actos), lower blood sugar. Studies published in 2007 confirmed some earlier evidence that both drugs could, in rare instances, cause liver and heart failure. The surprise came with study results showing that rosiglitazone — but not pioglitazone — markedly increases the risk of heart attack, as well as overall risk of dying from heart disease. The absolute risk is small: about one additional heart attack or cardiac death in 1,000 people taking the drug. The FDA put a “black box” warning on it, but rosiglitazone stayed on the market, unlike rofecoxib (Vioxx), the COX-2 painkiller that was pulled off in 2004 when it was found to cause heart problems.

No drug is entirely safe, and it would be impractical to require studies large enough to identify all of a drug’s problems as a condition of approval. Instead, the FDA needs more money — and clout — to make sure drugs are monitored for safety after they’re on the market and to take prompt action if necessary. Congress passed legislation in 2007 that would give the agency that funding and power, as well as make some other important reforms (a requirement that all clinical trials be recorded in a central registry, for example). Time will tell whether these changes make a difference and restore lost confidence in medication safety.

2. Waking up to a new health habit: Sleep

None of us needs a study to tell us that we feel better after a good night’s sleep. But research is showing that getting enough sleep — between seven and nine hours a night for most people — is one of the pillars of good health, along with exercise, eating plenty of fruit and vegetables, and staying slim.

No one study made a big splash in 2007, but the evidence has reached a critical mass. Studies have linked short and poor sleep to many modern maladies: diabetes, heart disease, high blood pressure, inflammation, stroke. Short sleep may be a factor in the obesity epidemic: sleep lab studies have shown that it alters the activity of leptin, the “fullness” hormone, and ghrelin, the “appetite” hormone.

Meanwhile, scientists are beginning to understand the sleeping brain and the role it plays in our mental lives and health. One popular theory is that we need sleep to store — and possibly attach meaning to — our memories. So if you make sleep a priority, you might improve your memory and your health.

3. Putting out the fire

When it’s under control, inflammation is a normal part of our immune response. But when it gets out of control, inflammation causes disease and pain, and fanning the flames is a protein called tumor necrosis factor-alpha (TNF-alpha).

In the 1990s, researchers genetically engineered a protein that blocks TNF-alpha. The FDA approved the fruits of this labor, etanercept (Enbrel), in 1998.

Now two others — infliximab (Remicade) and adalimumab (Humira) — are on the market, and a third — certolizumab — is waiting in the wings.

The medications have greatly improved the treatment of several inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (a condition that affects the spine and the sacroiliac joints), and Crohn’s disease, a bowel disorder. A combination of a TNF-alpha blocker and methotrexate, a standard antirheumatic drug, is twice as effective as methotrexate alone in the treatment of rheumatoid arthritis. Sales of the TNF-alpha blockers have more than tripled since 2002, according to IMS Health.

The TNF-alpha blockers have serious drawbacks: they’re expensive ($10,000 to $25,000 annually per patient), can result in serious infections, and have been linked to cancer, particularly lymphoma. But by tackling inflammation at its roots, they may be paving the way for a new approach to treating many diseases. In 2007, National Institutes of Health researchers proposed using TNF-alpha inhibition to treat brain diseases with an inflammatory component, such as Alzheimer’s and Parkinson’s disease.

4. A better mammogram?

For most women, mammograms do a good job of finding breast cancer early. But no screening test is perfect, and the x-ray images of the traditional mammogram miss some cancers.

Magnetic resonance imaging (MRI) scans provide extremely detailed images of soft tissues. Two studies of high-risk women published in 2007 compared breast MRIs with other screening tests — including standard x-ray mammography, ultrasound, and clinical breast exams — and found that MRI scans identified cancers the other techniques missed. The MRIs were especially helpful in women with dense breasts, which have more glandular and connective tissue — and less fat — than normal.

The American Cancer Society revised its screening recommendations to say that women at high risk for breast cancer should get a breast MRI every year, in addition to a regular mammogram. This high-risk group includes women who have a BRCA1 or BRCA2 breast cancer gene mutation or whose first-degree relatives (parents, siblings, children) do. The cancer society guidelines are part of a long-term trend of increasingly complicated screening protocols, tiered by risk group.

MRI scans won’t replace conventional mammography any time soon. Cost and access are major obstacles. In addition, the current technology would generate too many false positives — finding lumps that turn out not to be cancer and increasing the number of unnecessary biopsies. The technology will probably improve, though. Over the next few years, MRIs may become a major part of breast screening programs, particularly for women with dense breast tissue.

5. Peeking into the brain

When doctors diagnose Alzheimer’s disease, depression, and many other conditions related to the brain, they have only symptoms to go by. But with advances in imaging technology, researchers are getting the brain to give up its secrets, and more direct tests may soon be possible.

Functional magnetic resonance imaging scans are allowing researchers to measure minute changes in brain activity. Voltage-sensitive dyes can isolate specific brain circuits. Positron emission tomography (PET) scans use radioactive tracers and CT scanners to generate exquisitely detailed images of brain metabolism.

University of Pittsburgh researchers have developed a PET tracer — dubbed PIB, short for Pittsburgh Compound B — that labels beta amyloid, the protein fragment that many Alzheimer’s researchers believe is the main cause of the disease.

Researchers are heralding PIB testing as a breakthrough. It could — at last — provide a way to detect Alzheimer’s disease before symptoms appear. Treatments directed at reducing beta amyloid are under development. If beta amyloid plaque could be found with PIB testing, these medications might be given early in the disease, before symptoms occur.