Target Health Contribution to New Drug Approvals 2011


FDA has recently announced that 35 new drugs were approved this year (see Regulatory Affairs below). As in previous years, Target Health has made a major contribution to at least one of the FDA drug approvals. For 2 of the approvals this year, 1) Target e*CRF® was used to support a novel approach to cancer therapy; and 2) Target Health met with FDA at the pre-IND meeting, prepared and submitted the IND, obtained orphan drug designation and implemented Target e*CRF for the pivotal trial.


This year, Target Health will submit an original eCTD NDA, and has already submitted 4 original INDs, with 2 more to be submitted before the end of the year. Bravo to Dr. Glen Park, Sr. Director at Target Health, and the best team in the industry.


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. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at:

Is Collective Planetary Brain-Storming the New World Order?





Intelligence not wealth is the new status measure. Gamers have decoded an AIDS protein that stumped 1) ___ for 15 years. They did it in just three weeks.


One no longer needs a Ph. D. to make an incredible scientific breakthrough. A 15-year-old AIDS problem was recently solved in just three weeks using a new online game site that allows users to contribute in decoding complex 2) ___. Fold-it users incredibly modeled the enzyme, Mason-Pfizer monkey virus (M-PMV) retroviral protease, in a manner that matched crystalline 3) ___ observed by scientists. Simply put, Fold-it allows users to predict the shape of a protein and map it, using a game-like structure. The better the model, the more 4) ___ you get.


In this case, however, scientists experimented with giving users three weeks to create a 5) ___ of a protein that scientists haven’t been able to model on the molecular level themselves. At the end of the three-week period, scientists compared the best models to x-ray crystallography of the protein. They discovered that at least one group of players had determined the correct structure for it, according to the 6) ___ Blog

The findings were published in structural and molecular biology section of the September 18, 2011 version of the journal Nature. Fold-it has gained over 236,000 players since it started in 2008.


Amazingly, according to PC Magazine, few of the players involved had any background in biochemistry at all.


Fold-it was developed by researchers at the University of Washington with the hopes of bringing a human element back to the modeling process. “People have spatial reasoning skills, something computers are not yet good at,“ Seth Cooper,’s lead developer, said in a news release according to MSNBC. “Games provide a framework for bringing together the strengths of 7) ___ and humans.”


However, the protein revelation is just one small part of the AIDS puzzle. It appears in the monkey version of AIDS, and plays a key role in the multiplication of the virus. With an accurate model of this protein, drugs can be created that could potentially help stymie the multiplication of the virus in 8) ___.


UPDATE: While the open time frame for creating the structure online was 3 weeks, the correct answer was found in just 10 days.


ANSWERS: 1) researchers; 2) proteins; 3) structures; 4) points; 5) model; 6) Fold-it; 7) computers; 8) humans

Marie Curie 1867 – 1934





A new Google Doodle celebrates the birth of scientist Marie Curie on November 7 in 1867. Born in Poland, Curie moved to Paris in her early 20s to study mathematics and physics at the Sorbonne. She and husband Pierre are remembered for their groundbreaking work in physics and, later, in chemistry.


Google’s Doodle appears a watercolor or hand drawn depiction of Curie as one might imagine she spent a great deal of her time: sitting at a wooden table, jugs and beakers of chemicals at the ready, mixing and testing in front of windows revealing the blue skies of Paris beyond. The Google logo is sketched in pastel tones behind Curie.


Marie and Pierre were awarded their first Nobel prize in 1903 after discovering polonium and radium, alongside the man who discovered radioactivity, Henri Becquerel. Curie named polonium after Poland, her country of origin. In 1911, Curie won a second Nobel prize, this time for her work in chemistry. Curie also championed the use of radium in medicine and helped to develop portable x-ray units for use in the first world war. Curie’s war efforts went far beyond this, however; she became director of the Red Cross radiological service and gathered supplies, vehicles, and monetary donations to support the cause.


In 1914, Curie became even more involved in the war and, with her 17-year-old daughter Irene, headed to the front lines. There, they worked at casualty clearing stations, performing x-rays on injured soldiers and training orderlies and doctors in radiology.


Curie died of bone marrow disease pernicious anemia, caused by years of exposure to radiation, in 1934. She was interred at the Pantheon in Paris, the first woman to receive such a posthumous honor. In 2010, HarperCollins published Radioactive: Marie & Pierre Curie: A Tale of Love and Fallout. Curie was the most influential female scientist of her time.


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Light Therapy Designed That Targets and Destroys Cancer Cells in Mice


Current photodynamic therapy is not specific for cancer cells and can result in damage to surrounding normal tissue. As a result, an article published online in Nature Medicine (6 November 2011), a light-based therapy has been designed that allows the selective destruction of tumor cells in mice without harming surrounding normal tissue. According to the authors, this method of cancer therapy could theoretically work against tumors in humans, such as those of the breast, lung, prostate, as well as cancer cells in leukemias.


This new type of treatment, called photoimmunotherapy, or PIT, uses light to rapidly and selectively kill cancer cells. To create their PIT, the authors coupled a monoclonal antibody or MAb, which recognizes specific proteins on the surface of cancer cells, with a photosensitizer – a molecule that, when exposed to light of the appropriate wavelength (near-infrared), rapidly damages cells. The hope was that the combined photosensitizer/MAb would, by delivering the photosensitizer to cancer cells targeted by the MAb, selectively kill those cells after exposure to near-infrared light.


After evaluating a large number of photosensitizers, the authors found that a near infrared fluorescent dye called IR700 had the most favorable chemical properties. IR700 was then linked to three different MAbs, including antibodies that target 1) HER2, which is overexpressed by some breast cancers; 2) EGFR, which is overexpressed by some lung, pancreatic, and colon cancers; and 3) PSMA, which is overexpressed by prostate cancers. The authors found that when cancer cells bound MAb-IR700 and were exposed to near-infrared light, the targeted cells rapidly died whereas cells lacking the ability to bind the complex were unharmed. When the complex was tried in mouse models of cancer, even a single dose of near-infrared light resulted in dramatic tumor shrinkage in mice that had been given MAb-IR700. Like visible light, infrared light has a range of wavelengths that range from red light to violet; near-infrared light is closest in wavelength to visible light.


Photoimmunotherapy using MAb-IR700, unlike conventional photosensitizers which can cause damage to healthy tissue, does not appear to harm normal cells. Whereas the light that is required to activate conventional photosensitizers can penetrate through only about 0.8 centimeters of tissue (about a third of an inch), the near-infrared light used to activate IR700 can penetrate tissue to a depth of several centimeters (One centimeter is .39 inch).


The study also found antibody doses required for diagnosis were significantly lower than those required for therapy. Nevertheless, after MAb-IR700 exposure, the targeted tumors decreased in size and eventually disappeared, suggesting a potential means of controlling cancers with far lower doses of MAb than are usually administered to cancer patients. Because the MAb-IR700 compound also emits a small amount of light, it can be used to monitor therapy as well.

Pre-Birth Brain Growth Problems Linked to Autism


The prefrontal cortex is involved in various higher order functions such as language and communication, social behavior, mood, and attention. Children who have autism tend to show deficits in such functions. It has been reported that autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. Now, according to an article published in the Journal of the American Medical Association (2011;306:2001-2010), children with autism have been shown to have more brain cells in the PFC and heavier brains compared to typically developing children. This small, preliminary study provides direct evidence for possible prenatal causes of autism.


For the investigation, prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and who died between 2000 and 2006.


The main outcome measures were mean neuron number and size in the DL-PFC and M-PFC compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed


Results showed that children with autism had 67% more neurons in the prefrontal cortex and heavier brains for their age compared to typically developing children. Since these neurons are produced before birth, the study’s findings suggest that faulty prenatal cell birth or maintenance may be involved in the development of autism. Another possible factor that may contribute to the neuronal excess is a reduction in apoptosis, or programmed cell death, which normally occurs during the third trimester and early postnatal life.


According to the authors, the relative scarcity of tissue from very young children may limit future research as well, but efforts to include a larger number of samples are needed to confirm these findings and to identify patterns of age-related changes in autism.


Conclusion In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.

Obesity, Physical Inactivity, and Colonic Diverticular Disease Requiring Hospitalization in Women


Lifestyle factors other than dietary fiber intake and risk for colonic diverticular disease have only been examined in few studies. As a result, a study published online in the American Journal of Gastroenterology (18 October 2011) was performed to investigate the association between obesity and physical inactivity and diverticular disease in a population-based cohort of women.


The investigation was a prospective population-based cohort study in 36,592 women, born 1914-1948, in the Swedish Mammography Cohort. Evaluations occured between 1997-2009. Body mass index (BMI; kg/m2), physical activity, diet, smoking, and other lifestyle factors were collected at baseline through questionnaires. Cases of diverticular disease were identified from the Swedish Patient and Death Registers. Relative risks (RRs) of diverticular disease requiring hospitalization (or being the cause of death) according to BMI and physical activity. The multivariable models were adjusted for age; intake of dietary fiber; diabetes; hypertension; use of acetylsalicylate acid, non-steroid anti-inflammatory drug, or steroid medication; alcohol consumption; smoking; and educational level.


During 12 years of followup, 626 cases of incident diverticular disease requiring hospitalization were found. Two women were registered in the National Death Register only. In multivariable analysis, women with BMI >25-30 had a 29% increased risk, and obese women (BMI >30) had 33% increased risk of diverticular disease compared to women with BMI <25. Exercise <30 min/day increased the risk for disease by 42% compared with exercise >30 min/day. Ninety-eight subjects were hospitalized due to complications; perforation or abscess. Women with BMI >30 had a twofold (P=0.028) increased risk for complicated disease.


According to the authors, overweight, obesity, and physical inactivity among women increase diverticular disease requiring hospitalization.

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


35 Innovative New Drugs Approved by FDA in Fiscal 2011


Over the past 12 months, the FDA has approved 35 new medicines. This is among the highest number of approvals in the past decade, surpassed only by 2009 (37). Many of the drugs are important advances for patients, including: two new treatments for hepatitis C; a drug for late-stage prostate cancer; the first new drug for Hodgkin’s lymphoma in 30 years; and the first new drug for lupus in 50 years.


In a report released today, FY 2011 Innovative Drug Approvals, the FDA provided details of how it used expedited approval authorities, flexibility in clinical trial requirements and resources collected under the Prescription Drug User Fee Act (PDUFA) to boost the number of innovative drug approvals to 35 for the fiscal year (FY) ending Sept. 30, 2011.


The report shows faster approval times in the United States when compared to the FDA’s counterparts around the globe. Twenty-four of the 35 approvals occurred in the United States before any other country in the world and also before the European Union, continuing a trend of the United States leading the world in first approval of new medicines.


Among the new drugs approved in FY 2011, a number are notable for their advances in patient care and for the efficiency with which they were approved:


— Two of the drugs – one for melanoma and one for lung cancer – are breakthroughs in personalized medicine. Each was approved with a diagnostic test that helps identify patients for whom the drug is most likely to bring benefits;


— Seven of the new medicines provide major advances in cancer treatment;


— Almost half of the drugs were judged to be significant therapeutic advances over existing therapies for heart attack, stroke and kidney transplant rejection;


— Ten are for rare or “orphan“ diseases, which frequently lack any therapy because of the small number of patients with the condition, such as a treatment for hereditary angioedema;


— Almost half (16) were approved under “priority review,“ in which the FDA has a six month goal to complete its review for safety and effectiveness;


— Two-thirds of the new approvals were completed in a single review cycle, meaning sufficient evidence was provided by the manufacturer so that the FDA could move the application through the review process without requesting major new information;


— Three were approved using “accelerated approval,“ a program under which the FDA approves safe and effective medically important new drugs quickly, and relies on subsequent post-market studies to confirm clinical benefit. For example, Corifact, the first treatment approved for a rare blood clotting disorder, was approved under this program; and


Thirty-four of 35 were approved on or before the review time targets agreed to with industry under PDUFA, including three cancer drugs that FDA approved in less than six months.

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


The Universality of Medicine


By Mark L. Horn, MD, MPH, CMO, Target Health Inc.


With all the turbulence in the world, including the medical world, perhaps it’s justifiable, and it’s certainly an enjoyable respite, to relate some personal observations that offer a dollop of optimism in an unsettled and often scary world.


I’ve just returned from the annual meeting of the American College of Rheumatology (ACR) in Chicago.  As always, this annual professional sojourn, with its opportunities for learning, networking, and simple reconnection with old friends, offers much needed professional and personal rejuvenation.  Upon reflection, this year’s meeting offered something more.  There was an injection of unexpected optimism from observing how international collaboration was embraced by the attendees; physicians and allied health professionals engaged in the shared, and noble, objective of providing the very best care for their patients through leveraging a global pool of knowledge and expertise.


As is undoubtedly the case for many (likely most) major US medical subspecialty events, the Rheumatology meeting has become increasingly international over the years.  While the ACR undoubtedly knows the precise percentage of attendance from outside the US, the number of international attendees was manifestly large and diverse; the impression exists that it grows each year.  Sometime during the event the thought intruded that many of these physicians represented countries that are not (to be gentle), on friendly terms; in fact, for many attendees the relationships among their countries at the international level can be charitably described as ?frosty’.


Yet, within the confines of the Convention Center, none of this seemed at all relevant.  The world’s rheumatology community had come together to share research findings, best practices, and accumulated clinical insights.  Difficult cases were presented for discussion and assistance, clinical dilemmas explored, questions asked, insights sought; unsurprisingly, in the quest for answers the nationality of the speakers was irrelevant.  All that mattered, the only goal, was trying to assure that patients with rheumatic disease receive the most up-to-date interventions and care, wherever they live.  This was an international caring community of like-minded individuals united in a shared and admirable goal.


While probably not a representative or reproducible model, (politics, after all, cannot be indefinitely denied), for a few days in Chicago the seemingly insurmountable tribulations of a troubled world were set aside to address, and hopefully ameliorate, the suffering of some of its most distressed inhabitants.


It was a pleasure to be part of it.

Target Health ( a full service e*CRO, is committed to serve the pharmaceutical community through knowledge, experience, technology and connectivity. Target Health strives to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. Target Health Inc. has fulltime staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. Target Health is committed to the paperless clinical trial and has developed a full suite of eClinical Trial software including:

1) Target e*CRF® (EDC Made Simple)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target e*Pharmacovigilance™

6) Target e*Monitoring™

7) Target Newsletter®

8) Target e*CTR™ (eSource, electronic medical record for clinical trials).


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