Science Weekly podcast: Why scientists love Germany

Filed Under Uncategorized | Comments Off on Science Weekly podcast: Why scientists love Germany

We visit the European Space Agency’s operations centre, and get a taste of some of the most exciting research being carried out in Germany

Congratulations to Shire


Shire HGT (human genetic therapies) has announced that the European Commission has approved FIRAZYR (icatibant) for self-administration, after training in subcutaneous injection technique by a healthcare professional, for the symptomatic treatment of acute attacks of Hereditary Angioedema (HAE). FIRAZYR is the first and only treatment for acute Type I and Type II HAE attacks licensed for self-administration in Europe.


Target Health started working with Jerini AG (Berlin) back in 2003 prior to its acquisition by Shire. At that time our good friend and colleague Dr. Bernd Rosenkranz, was VP of Clinical Development. We started with a successful IND submission and approval of the HAE orphan indication.


The study was designed to evaluate safety, local tolerability, convenience and efficacy of self-administered FIRAZYR for the symptomatic treatment of acute HAE attacks in FIRAZYR naive and non-naive HAE patients. Based on an analysis of initial data from this ongoing study, time from injection to symptom relief for self-administered FIRAZYR was consistent with healthcare professional-administered FIRAZYR therapy in the previously published FAST-1 and FAST-2 studies.


FIRAZYR is currently approved in 37 countries worldwide, including the countries of the European Union. On February 28, 2011, Shire announced the submission of a complete response to the not approvable letter issued by the FDA regarding its NDA for FIRAZYR.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website at:

Sunlight Can Influence the Breakdown of Medicines in the Body

Credit: iStockphoto/Michiel De Boer


A study from the Swedish medical university Karolinska Institutet has shown that the body’s ability to break down medicines may be closely related to exposure to sunlight, and thus may vary with the 1) ___. The findings offer a completely new model to explain individual differences in the effects of drugs, and how the surroundings can influence the 2) ___ ability to deal with toxins.


The study will be published in the scientific journal Drug Metabolism & Disposition (2011 10.1124/dmd.111.038125) and is based on nearly 70,000 analyses from patients who have undergone regular monitoring of the levels of drugs in their 3) ___. The drugs taken by these patients were used to suppress the 4) ___ system in association with organ transplants. Samples taken during the winter months were compared with those taken late in the summer.


A more detailed analysis showed that the concentrations of drugs such as tacrolimus and sirolimus, which are used to prevent 5) ___ following transplantation, vary throughout the year in a manner that closely reflects changes in the level of vitamin D in the body. The ability of the body to form vitamin D depends on 6) ___, and the highest levels in the patients taking part in the study were reached during that part of the year when the levels of the drugs were lowest.


The connection between sunlight, vitamin D and variations in drug concentration is believed to arise from the activation by vitamin D of the detoxification system of the 7) ___ by increasing the amount of an enzyme known as CYP3A4. This enzyme, in turn, is responsible for the breakdown of tacrolimus and sirolimus.


“If the breakdown capacity increases, then higher 8) ___ of a drug are normally required in order to achieve the same effect. More research will be needed to confirm the results, but CYP3A4 is considered to be the most important enzyme in drug turnover in the body, and the results may have significance for many drugs,” says Jonatan Lindh at the Department of Laboratory Medicine and one of the scientists who carried out the study.


The effects of vitamin D on CYP3A4 have previously been demonstrated in experiments in cell cultures. But the study shows for the first time that the mechanism can play an important role in the pharmacological treatment of patients, and it shows for the first time that variation in exposure to sunlight may affect the sensitivity of individuals to 9) ___.


ANSWERS: 1) seasons; 2) body’s; 3) blood; 4) immune; 5) rejection; 6) sunlight; 7) liver; 8) doses; 9) drugs

Yes, the American Founding Fathers DID Support Vaccinations


Benjamin Franklin’s son Franky died of smallpox
Collection of Ann C. Boswell


During the early years of the U.S., inoculation was used to quell smallpox, the deadliest scourge of the day. Such preventive public health measures framed the early days of our nation as tightly as the “unalienable rights” of life, liberty and the pursuit of happiness. John Adams was inoculated in 1764. Twelve years later, while he was in Philadelphia declaring American independence, his wife and children were inoculated as an epidemic raged in Boston. George Washington ordered his soldiers to be inoculated in 1777 because more men were dying from smallpox than to Redcoat muskets. Thomas Jefferson, who avidly followed the scientific literature on the subject, inoculated himself and his children in 1782. However, the most eloquent advocate of smallpox inoculation was Benjamin Franklin.


In 1721, the Puritan minister Cotton Mather promoted inoculation in partnership with a Boston physician named Zabdiel Boylston, who risked life and limb by inoculating his children, his black servants and many of his patients. Among those opposing Mather’s efforts was Franklin’s brother James, the contrarian publisher of The New England Courant. Aside from the inherent danger of the procedure, James Franklin argued that religious zealots had no business practicing medicine. He was hardly alone; many colonists considered inoculation a breach of the Sixth Commandment (“Thou shalt not kill”).


Inoculation involved lancing open a wound and implanting dried scabs or fresh pus containing variola (the virus that causes smallpox) under the skin of a healthy, uninfected person. Said to have originated in China, it was commonly practiced across the Far East and the Ottoman Empire. The procedure typically caused a milder form of smallpox and conferred lifelong immunity. Still, many people became ill, and not a few died. Moreover, it was feared that the inoculated would infect others.


Yet after an initial silence (perhaps out of fear of enraging his older brother), Benjamin Franklin became one of the colonies’ leading proponents of inoculation, trumpeting his advocacy in the pages of his own newspaper, The Pennsylvania Gazette. Reporting on 72 Bostonians inoculated in March 1730, for example, he noted that only two died while “the rest have recovered perfect health. “Of those who had it in the common way,” he continued, “’tis computed that one in four died.” In the following decades Franklin compiled and published quantitative studies on inoculation’s value, working with several physicians at the Pennsylvania Hospital, an institution he helped found, and with the famed British clinician William Heberden. He was also concerned that the high cost of the procedure – more than many colonists’ annual income – made it inaccessible to the poorest Americans. In 1774, to counter this inequity, Franklin established the Society for Inoculating the Poor Gratis.


Haunting these activities was a very personal ghost: that of Francis Folger Franklin, the younger of his two sons. Franky, as his parents called him, was born in 1732 – a golden child, his smiles brighter, his babblings more telling and his tricks more magical than all the other infants in the colonies combined. Benjamin advertised for a tutor when the boy was only 2. When he died of smallpox at age 4, the Franklins were beyond condolence. His tombstone was inscribed, “The delight of all who knew him.” Rumors abounded that Franky had died from an inoculation gone awry. The gossip led the grieving Franklin to declare that his son had never been inoculated because he was suffering from “flux,” or protracted diarrhea. Franklin insisted that Franky “receiv’d the distemper” – smallpox – “in the common way of infection,” and that “inoculation was a safe and beneficial practice.”


Inoculation was eventually replaced by the far safer method of vaccination, which uses a milder virus to induce immunity. An English country doctor named Edward Jenner made this discovery in 1796 after noting that local milkmaids who contracted the annoying but harmless cowpox infection on their hands remained healthy during lethal smallpox epidemics.


Helicobacter Pylori Eradication with a Capsule Containing Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline Given with Omeprazole Versus Clarithromycin-Based Triple Therapy


Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. As a result, a study published in The Lancet (Early Online Publication, 22 February 2011) was performed to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication.


The investigation was a randomized, open-label, non-inferiority, phase 3 trial in adults with recorded H pylori infection. The study was performed in 39 sites in Europe, and compared the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy), versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy).


The study was designed as a non-inferiority trial but was powered to detect superiority. The primary outcome was H pylori eradication, established by two negative 13C urea breath tests at a minimum of 28 and 56 days after the end of treatment. The assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (i.e., all participants randomly assigned treatment).


During the study, 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% in the quadruple therapy group versus 55% in the standard therapy group (p<0.0001). Safety profiles for both treatments were similar with the main adverse events being gastrointestinal and CNS disorders.


According to the authors, quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.

Lung Volumes and Emphysema in Smokers with Interstitial Lung Abnormalities


Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. As a result, a study published in the New England Journal of Medicine (2011;364:897-906), looked for interstitial lung abnormalities in 2,416 (96%) of 2,508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers.


Results showed that interstitial lung abnormalities were present in 194 (8%) of the 2,416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (−3%; P<0.001) and −910 Hounsfield units (−10%; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking.


According to the authors, in smokers, interstitial lung abnormalities – which were present on about 1 of every 12 HRCT scans – were associated with reduced total lung capacity and a lesser amount of emphysema.

Timing of Solid Food Introduction and Risk of Obesity in Preschool-Aged Children


According to an article published in Pediatrics (2011;127:e544-e551), a study was performed to examine the association between timing of introduction of solid foods during infancy and obesity at 3 years of age.


The study evaluated 847 children in Project Viva, a prospective pre-birth cohort study. The primary outcome was obesity at 3 years of age (BMI for age and gender 95th percentile). The primary exposure was the timing of introduction of solid foods, categorized as <4, 4 to 5, and 6 months. An analysis was performed for infants who were breastfed for at least 4 months (“breastfed”) and infants who were never breastfed or stopped breastfeeding before the age of four months (“formula-fed”), adjusting for child and maternal characteristics, which included change in weight-for-age z score from 0 to 4 months-a marker of early infant growth.


Results showed that in the first 4 months of life, 568 infants (67%) were breastfed and 279 (32%) were formula-fed. At age 3 years, 75 children (9%) were obese. Among breastfed infants, the timing of solid food introduction was not associated with odds of obesity. However, among formula-fed infants, introduction of solid foods before 4 months was associated with a sixfold increase in odds of obesity at age 3 years; the association was not explained by rapid early growth (odds ratio after adjustment: 6.3).


According to the authors, among formula-fed infants or infants weaned before the age of 4 months, introduction of solid foods before the age of 4 months was associated with increased odds of obesity at age 3 years.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

FDA Approves Device to Maintain Blood Flow During Artery Bypass Brain Surgery – Option For Those at Greater Risk For Stroke During Standard Bypass Surgery


Standard bypass surgery in the brain requires clipping the artery to halt blood flow during the procedure. The surgery is not considered safe for about 1,000 patients annually in the United States because temporarily shutting off their blood flow would put them at high risk of stroke. The group includes patients ages 13 and older who have an enlarged, weak area in a brain artery (cerebral aneurysm), tumors at the base of the skull that could impact blood flow in brain arteries, or other issues that could complicate conventional surgery.


The FDA has approved a surgical kit that allows neurosurgeons to reroute blood flow around an aneurysm or a tumor in the brains of patients at greater risk of stroke during standard bypass surgery. The ELANA (Excimer Laser Assisted Non-Occlusive Anastamosis) Surgical Kit allows neurosurgeons to create a bypass without shutting off the blood flow. It consists of a small platinum ring and a hand piece connected to a surgical laser and suction tubing.


To create the bypass, a surgeon sutures the ring and a section of replacement blood vessel onto the surface of the affected artery. Once attached, the surgeon tunnels the tip of the laser hand-piece down the open end of the replacement blood vessel until the tip of the laser touches the ring. The laser then cuts a circular hole in the affected artery, and suction removes the cut tissue. The process is repeated with a second replacement blood vessel. Once both replacement blood vessels are in place, the open ends of the two replacement blood vessels are sutured together to complete the path around the aneurysm or tumor.


The FDA approved the ELANA Surgical Kit as a Humanitarian Use Device, which is a device that is designed to treat or diagnose a disease or condition in fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate the safety of the device and that the probable benefit outweighs the risk of illness or injury. The company must also show that no comparable devices are available to treat or diagnose the disease or condition.


The clinical data in support of approval demonstrated that a bypass created using the ELANA kit had the same types and similar incidences of adverse events reported in the medical literature as conventional bypass procedures. A patient should not undergo laser bypass surgery using the Elana kit if the arteries show signs of arteriosclerosis or calcification at the surgery site, the walls of the affected artery are thicker than a carotid artery, or have an abnormality. Bypass surgery with the Elana should not be done on an aneurysm or on vessels other than large (> 2.5 mm), intracranial arteries.


In some cases, the laser does not completely cut through an artery wall leaving a tissue flap that potentially could block blood flow and result in an embolism. As part of the approval, the FDA required a post approval registry study to collect performance information about the kit, including flap retention rate, mortality, and stroke. The ELANA Surgical Kit is manufactured by Elana, in Utrecht, Netherlands.


For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.


Target Health Inc.
261 Madison Avenue
24th Floor
New York, NY 10016

Joyce Hays, CEO

Jules T. Mitchel, President