Life Sciences Summit Meeting on September 25 and 26, 2010

Target Health is pleased to announce that Dr. Jules Mitchel will be moderating a Business Workshop at the Life Sciences Summit being held this year at the Hyatt Regency 1717 Motor Parkway, Hauppauge, New York, 11788 on September 25 and 26, 2010.

The workshop is entitled: “Successful Product Development: A Practical Guide to Doing It Right.” Our panelists include:

1. Richard Clark, MD, Professor at SUNY Stony Brook School of Medicine and has just set up a company with technology he developed

2. Braham Shroot, PhD, CEO of Signum Biosciences and former CSO at Barrier Therapeutics

3. Henry Pan, MD, PhD, CEO of Renascions and Pan Consulting Associates LLC and former EVP at DuPont Merck and VP of Clinical R&D at BMS.

4. Mark Horn, MD, MPH, worked in licensing at Pfizer for 5 years and current CMO at Target Health

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. 

Surprise Breast Cancer Source

BRCA1 structure Image: Wikimedia commons, Lijealso

Some breast cancer 1) ___ may not originate from stem cells as previously believed, according to a study published in the September 3rd issue of Cell Stem Cell. The discovery is an important step in the development of treatments for these cancers. “Understanding the origins of these types of breast cancer is not only critical for developing preventative strategies against the disease but also for developing new targeted therapies,” said Matthew Smalley, a mammary cell biologist at the Breakthrough Breast Cancer Centre in London and lead author on the study.

For years, scientists have believed that most breast cancers originated from basal stem cells, which have the ability to give rise to any of the breast tissues. But comparing mice expressing mutant versions of the BRCA1 gene, which is known to cause breast cancer, in different breast cell types, Smalley and his colleagues discovered that BRCA1 tumors actually come from progenitor cells, which can only differentiate into a single tissue type.

The BRCA1 gene, which is expressed in all cells, repairs breaks in the cell’s DNA when functioning correctly. People carrying a mutated version of the gene, however, are more likely to get tumors in several tissues, including the breast and ovaries. While the BRCA1 gene doesn’t cause the majority of breast cancers, carriers of the mutated gene have a much higher chance – between 50 to 80% – of getting either breast or ovarian cancer during their lifetime, and the cancers are aggressive.

Scientists used to think that these cancers came from the breast’s 2) ___ stem cells because the tumors and the basal stem cells express many of the same genes. Furthermore, because such tissue-specific stem cells are long-lived and divide frequently, some have suggested them as a likely source of many types of cancer.

To determine the true origin of BRCA1 tumors, Smalley and his colleagues inserted a mutant version of the gene into either basal stem cells or luminal progenitor cells, which give rise to the cells that line the 3) ___ gland duct. While both sets of mutation-bearing mice developed tumors, the tumors were not the same. The tumors in the mice with the mutated BRCA1 gene in their luminal progenitor cells appeared most like BRCA1 breast cancers in humans with regard to their aggressive growth and genetic markers. The tumors on the mice with the mutated BRCA1 gene in their basal stem cells, on the other hand, had characteristics of a different type of rare malignant epithelial cell cancer. It is possible that different types of breast 4) ___ derive from different cells of origin, said Smalley.

Smalley said he will continue to study how these and other tumors form, and what features they have in common with their origin cells, as a possible target for therapeutics. “If we can identify molecular features which these tumors have in common with the cells which we now know they originate from” he said, “we will have identified key aspects of the biology of these cancers which, when disrupted, will have 5) ___therapeutic benefit.” G. Molyneux, et al., “BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells,” Cell Stem Cell 7:403-17, 2010.

ANSWERS: 1) tumors; 2) basal; 3) mammary; 4) cancers; 5) therapeutic

Maggot Therapy

Written records have documented that maggots have been used since antiquity as a wound treatment. There are reports of the successful use of maggots for wound healing by Maya Indians and Aboriginal tribes in Australia. There also have been reports of the use of maggot treatment in Renaissance times. During warfare, many military physicians observed that soldiers whose wounds had become colonized with maggots experienced significantly less morbidity and mortality than soldiers whose wounds had not become colonized. These physicians included Napoleon’s surgeon general, Baron Dominique Larrey, who reported during France’s Egyptian campaign in Syria, 1798–1801, that certain species of fly destroyed only dead tissue and had a positive effect on wound healing.

A Wound Cleaned by Maggots

Dr. Joseph Jones, a ranking Confederate medical officer during the American Civil War, is quoted as follows, “I have frequently seen neglected wounds … filled with maggots … as far as my experience extends, these worms only destroy dead tissues, and do not injure specifically the well parts.” The first therapeutic use of maggots is credited to a second Confederate medical officer Dr. J.F. Zacharias, who reported during the American Civil War that, “Maggots … in a single day would clean a wound much better than any agents we had at our command … I am sure I saved many lives by their use.” He recorded a high survival rate in patients he treated with maggots.

During World War I, Dr. William S. Baer, an orthopedic surgeon, recognized on the battlefield the efficacy of maggot colonization for healing wounds. He observed one soldier left for several days on the battlefield who had sustained compound fractures of the femur and large flesh wounds of the abdomen and scrotum. When the soldier arrived at the hospital, he had no signs of fever despite the serious nature of his injuries and his prolonged exposure to the elements without food or water. When his clothes were removed, it was seen that “thousands and thousands of maggots filled the entire wounded area.” To Dr. Baer’s surprise, when these maggots were removed “there was practically no bare bone to be seen and the internal structure of the wounded bone as well as the surrounding parts was entirely covered with most beautiful pink tissue that one could imagine.” This case took place at a time when the death rate for compound fractures of the femur was about 75-80%.

While at Johns Hopkins University in 1929, Dr. Baer introduced maggots into 21 patients with intractable chronic osteomyelitis. He observed rapid debridement, reductions in the number of pathogenic organisms, reduced odor levels, alkalinization of wound beds, and ideal rates of healing. All 21 patients’ open lesions were completely healed and they were released from the hospital after two months of maggot therapy.

ONCOLOGY

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Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer

Patients with metastatic non-small-cell lung cancer (NSCLC) have a substantial symptom burden and may receive aggressive care at the end of life. In order to evaluate different treatment modalities., a study published in the New England Journal of Medicine (2010; 363:733-742), examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease.

The study randomly assigned patients with newly diagnosed metastatic NSCLC to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records.

Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P=0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P=0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P=0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P=0.02).

Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival.

Prevalence and Incidence of Hypertension in Adolescent Girls

According to an article published in the Journal of Pediatrics (2010;157: 461-467), a study was performed to estimate the prevalence and incidence of hypertension and prehypertension and associated factors in adolescent girls.

A total of 2368 girls (49% Caucasian, 51% African-American) aged 9 or 10 years enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study had blood pressure, height, and weight measured at annual visits through age 18 to 19 years. Prevalence and incidence of hypertension and prehypertension were calculated.

Results show that on the basis of 2 visits, hypertension prevalence was approximately 1% to 2% in African-American girls and 0.5% in Caucasian girls. Incidence 8 years later was 5.0% and 2.1%, respectively. Obese girls had higher prevalence (approximately 6-fold higher) and incidence (aprroximately 2- to 3-fold higher) compared with girls of normal weight. Similar patterns were found for prehypertension, except that prehypertension occurred more in older girls than younger girls. Dietary factors (lower intake of fiber, potassium, magnesium, and calcium, and higher intake of caffeine and calories) were each associated with hypertension incidence (all P < .05). In multivariate analysis, higher body mass index (P < .001) and lower potassium intake (P = .023) were independently associated with incidence of hypertension.

According to the authors, hypertension occurred early in childhood and was related to obesity and other modifiable lifestyle factors. The authors added that clinicians should monitor blood pressure during childhood and provide focused diet and physical activity guidance to minimize the development of hypertension.

Chefs’ Opinions About Reducing the Calorie Content of Menu Items in Restaurants

Modifying the energy content of foods, particularly foods eaten away from home, is important in addressing the obesity epidemic. Chefs in the restaurant industry are uniquely placed to influence the provision of reduced-calorie foods, but little is known about their opinions on this issue.

A survey conducted among chefs attending US culinary meetings about strategies for creating reduced-calorie foods and opportunities for introducing such items on restaurant menus was published on line in Obesity (2 September 2010). The 432 respondents were from a wide variety of employment positions and the majority had been in the restaurant industry for >20 years.

Nearly all chefs (93%) thought that the calories in menu items could be reduced by 10–25% without customers noticing. To decrease the calories in two specific foods, respondents were more likely to select strategies for reducing energy density than for reducing portion size (P < 0.004). Low consumer demand was identified as the greatest barrier to including reduced-calorie items on the menu by 38% of chefs, followed by the need for staff skills and training (24%), and high ingredient cost (18%). The majority of respondents (71%) ranked taste as the most influential factor in the success of reduced-calorie items (P < 0.0001).

According to the authors, the results of the survey indicate that opportunities exist for reducing the energy content of restaurant items. The authors added that ongoing collaboration is needed between chefs and public health professionals to ensure that appealing reduced-calorie menu items are more widely available in restaurants and that research is directed toward effective ways to develop and promote these items.

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

Biosimilars, Interchangeables & Innovation – The Innovative Industry and the Affordable Care Act

It appears that the pharmaceutical industry is placing ever larger bets on biologically derived products, large complex biologically synthesized molecules, as opposed to the smaller, chemically synthesized molecules which have been its historical strength. The reason is that despite the high cost of manufacture and the requisite high cost to patients, the return on investment has become higher for biologically derived medicines. Due to the promise of personalized medicine with its potential to more accurately target these expensive agents, increasing efficacy and safety margins, their value for patients and profitability for innovators are poised to grow.

The Affordable Care Act (Health Reform) incorporates provisions seeking to promote the discovery and development of biologics by threading the needle between innovation, access and cost. Reciprocating the pathway designed to expedite generic competition for small molecules, the Act defines a pathway for “interchangeable biosimilars’’, biological products with minor differences from the reference compound (differences virtually inevitable among competitors given the inherent variation in biologic syntheses) yet demonstrated to have “safety, purity, and potency” similar to the reference molecule. If switching between the reference and biosimilar compound can be shown to be safe and preserve efficacy, a product can be additionally designated as “interchangeable” and substituted for the reference product without the intervention of the prescribing physician.

In return for this expedited pathway for biosimilars, the innovative industry receives 12 years of exclusivity; no biosimilar application can be approved for twelve years after the first licensing (note: not the date of patent issue) of the reference product.

As with much of the Affordable Care Act, enabling regulations must be written, so the practical impact remains uncertain. However, the fact that key players, especially the trade association BIO, seem pleased is instructive. The Act seems to recognize and support the clinical and economic value of innovation while seeking to balance this support with the critical need for cost-containment. While the practical outcome remains unknowable, the intent seems “on-target” and our innovative colleagues should be reassured that policymakers seem supportive of their efforts. (Mark L. Horn, MD, MPH; CMO of Target Health)

FDA Launches New Organizational Performance Management System

The FDA has launched an innovative performance management system designed to advance the President’s commitment to transparency, public participation, and collaboration in the work of government. The system, called FDA-TRACK, will monitor more than 100 FDA program offices through data from key performance measures established each year. That data will be gathered monthly, analyzed and presented each quarter to FDA senior leadership. Importantly, the public will be able to track this data and the agency’s progress through the FDA-TRACK website.

FDA-TRACK is designed to be informative, encourage accountability among the people who work at the FDA, and make that work more transparent. It gives managers and employees a new way to measure their effectiveness in meeting goals to protect the public health and provides a way for the public to monitor agency activities.

Adapted from several successful state and local performance management models, FDA-TRACK hopes to set the standard for open government at the federal level. The system monitors performance indicators in four categories:

Common Measures – Agency-wide measures applicable to each of more than 100 program offices and may focus on the agency’s most recent priorities. Example: Increase the total number of employees who are trained in the Incident Command System, which helps the agency respond to emergencies.

Key Center Director Measures – Center-specific measures that are applicable to each Center and are central to the Center’s priorities and strategic goals. Example: Increase the FDA’s technical guidance by increasing the number of technical publications drafted, which enables the Center to better prepare industry and consumers.

Program Measures – Program office-specific measures that are applicable to the office and reflect work important to the public and to the FDA’s mission. Example: Monitor the percentage of 510(k) decisions meeting the 90-day Medical Device User Fee Act goal during a specific time period.

Key Projects – Program office-specific projects that are applicable to the office and important to the mission and objectives of the office. Performance for Key Projects is measured through achievement of the stated milestones within the project’s plan. Example: The development of a new risk-based approach for evaluating safety, effectiveness, and quality of new animal drugs.

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

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing.

Target Health has developed a full suite of eClinical Trial software including:

1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

Target Health’s Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.