Biotechnology Showcase 2012



On 11 January 2012, Dr. Jules T. Mitchel, President of Target Health Inc., will be chairing a panel at the Biotech Showcase™ 2012 meeting in San Francisco. The topic will be “Getting a Drug Approved as the FDA is Evolving.” The Biotech Showcase provides private and public life science companies the opportunity to present to an audience of investors and business development executives during the course of the industry’s largest annual healthcare investor conference.


Now in its fourth year, Biotech Showcase 2012 is expected to attract upwards of 1,500 attendees. The program includes lunch plenary sessions featuring top industry leaders and innovators speaking on industry- and time-relevant topics, as well as presentations from both private and public companies. Let us know if you will be attending.


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

Two Drugs Appear to Delay Progression of Breast Cancer




Breast cancer today is not what it was 20 years ago. Survival rates are climbing, thanks to greater awareness, more early detection, and advances in treatment. For roughly 200,000 Americans who are diagnosed with breast cancer each year, there are plenty of reasons to be hopeful.


Two drugs have been shown to delay by several months the time before advanced breast cancer worsens, potentially providing new options for women with that disease. Both drugs, pertuzumab from Genentech and everolimus from Novartis, also showed signs in clinical trials that they could prolong 1) ___, though it is too early to say that definitively. Results of the studies were presented this week at the San Antonio Breast Cancer Symposium and were published online in The New England Journal of Medicine (7 Dec 2011).


Pertuzumab is designed to complement Genentech’s big-selling drug 2) ___ for the roughly 20% of breast cancer patients whose tumors have elevated levels of a protein called Her2. Both pertuzumab and Herceptin block the action of the protein but in different ways. In a late-stage clinical trial involving 808 patients, women randomly chosen to receive pertuzumab, Herceptin and the chemotherapy drug docetaxel, went a median of 18.5 months before their tumors worsened or they 3) ___, a measure known as progression-free survival. That was significantly longer than the 12.4 months for those who received a placebo, Herceptin and docetaxel.


“We have an improvement in progression-free 4) ___ that is six months,” said Dr. José Baselga, chief of hematology and oncology at Massachusetts General Hospital, said in an interview. He said the addition of pertuzumab did not increase cardiac dysfunction, a worrisome side effect of Herceptin. Genentech and its parent company, Roche, have applied in the last few days for permission to market pertuzumab in the United States and 5) ___. Approval could help Roche recover from the recent decision of the FDA to revoke the approval of another Genentech drug, Avastin, for the treatment of breast 6) ___. Avastin had been approved based on a trial that showed it delayed the worsening of tumors by 5.5 months — almost as big a gain as seen now with pertuzumab. But the use of Avastin did not prolong 7) ___, and subsequent studies found a much smaller improvement in progression-free survival. That could make the FDA reluctant to approve pertuzumab unless it also helps women live longer. But Dr. Sandra J. Horning, head of cancer clinical trials at Genentech, said the pertuzumab results on 8) ___ progression were more trustworthy than the original Avastin results because the trial was conducted more carefully.


Novartis’s drug, everolimus, is a tablet that is already sold under the name Afinitor to treat kidney cancer and some rare tumors. Novartis plans to apply for the tablet’s approval as a breast cancer treatment by the end of the year. The clinical trial involved 724 postmenopausal women with hormone receptor-positive metastatic breast cancer. The women who took both everolimus and a drug called exemestane had a median progression-free survival of 7.4 months compared with 3.2 months for those who took a 9) ___ plus exemestane. Exemestane, also known by the brand name Aromasin, deprives tumors of estrogen, which can fuel their growth. Women in the study already had failed to benefit from other estrogen-depriving drugs. So perhaps it is not surprising that the control arm did not do that well on exemestane alone. “They put it up against a weak opponent,” said Dr. Peter Ravdin, a breast cancer specialist at the University of Texas Health Science Center at San Antonio, who was not involved in the study. But trial investigators said the comparison was valid because in daily practice, doctors often use exemestane when other 10) ___-blocking drugs fail. Everolimus works by inhibiting mTOR, a protein that often spurs tumor growth after tumors become resistant to hormone therapy.


Another drug – entinostat, from privately held Syndax Pharmaceuticals – might also be able to do that, according to the results of a small study presented in San Antonio. Women who received that drug plus exemestane had delayed tumor progression and also lived months longer than those who took exemestane alone. Those results will have to be confirmed in a larger trial, and it will be several years before entinostat can reach the market.


Everolimus costs about $7,000 a month when used for kidney cancer. The drug can have significant, even fatal, side effects like mouth sores, infections and lung inflammation. That could give some doctors pause about adding it to 11) ___ therapy.


Update: This past week, an exhaustive new report, put out by The Institute of Medicine, meant to address public fears about possible links between breast cancer and the environment, found evidence strong enough to make only a few firm recommendations, most already well known and none with a large proven benefit. The most consistent data suggest that women can reduce their risk by avoiding unnecessary medical radiation, forgoing hormone treatments for 12) ___ that combine estrogen and progestin, limiting alcohol intake and minimizing weight gain, the report found. Source: NYTimes, 10 Dec 2011, by Andrew Pollack


ANSWERS: 1) lives; 2) Herceptin; 3) died; 4) survival; 5) Europe; 6) cancer; 7) lives; 8) tumor; 9) placebo; 10) estrogen; 11) hormone; 12) menopause

Lunsford Richardson & Vicks Vaporub



In the 1890s patent medicines were everywhere. Lydia Pinkham tried to cure “female complaints” with her tonic of herbs and a heavy dose of alcohol. She succeeded. Later she made even more money marketing her pills and a “blood purifier.” Asa Soule, a teetotaling entrepreneur, never let ethics get in the way of his “Doyle’s Hop Bitters”, one of the most popular of the patent medicines and almost exclusively alcohol. It made him a millionaire even though it never really cured anything.




Lunsford Richardson (1854-1919), however, was different. When his young son, Smith, suffered recurring bouts of croup, Richardson simply wanted to make his son better. As a North Carolina pharmacist, he had some vague ideas of what might work. He turned out to be right. His brother-in-law was a doctor, so Richardson arranged to borrow the doctor’s laboratory to do some experimenting. At first none of his experiments paid off but then one day he came across a little-known Japanese extract and mixed it with some ingredients he had on hand to create a salve. This he rubbed on his son the next time the boy had croup. It seemed to help. Then he offered it to some of his neighbors for them to use on their own children. Again it seemed to help. That is when Lunsford Richardson began to market his “Croup and Pneumonia Cure.” His motivation wasn’t to make money – although he did amazingly well at that – but simply to help sick children.


Lunsford Richardson was a pharmacist from Selma, North Carolina, and the founder of Vick Chemical Company (which became Richardson Vicks Inc.). He died August 20, 1919. Lunsford was born in 1854 on a farm near Selma, North Carolina. He attended Davidson College, where he graduated with highest honors in Latin in 1875. He taught at The Little River Academy before he became a pharmacist. Lunsford bought a drugstore in Selma where he concocted and sold a menthol-laced ointment for “croupy” babies that he labeled “Vick’s” in honor of Dr. Joshua W. Vick, his brother-in-law who helped him get established in business. Later he sold the store in Selma and bought one in Greensboro. This was the Porter and Tate Drugstore – Dr. Porter was the uncle of William Sydney Porter, the author known as O. Henry.



While working in Greensboro, NC, Lunsford Richardson developed a number of home remedies under the name “Vicks.” This name was suggested to him from an advertisement for Vick’s Seeds, and Vick was also the last name of his brother-in-law, a family physician. It was short and easy to remember. Eventually there were 21 “Vicks Family Remedies.” The main product included menthol, a new and little known drug from Japan, added to a balm. Since the product was used only externally, there was no risk of stomach upset. It was originally called Vicks Croup and Pneumonia Salve before it became VapoRub.



Vick’s Croup and Pneumonia Salve in 1880


In 1898, he sold his drugstore and formed Lunsford Richardson Wholesale Drug company, one of only 4 wholesale drug companies in North Carolina. He sold the 21 Vicks products as well as other drugs. In 1905 he sold the wholesale drug company and founded Vicks Family Remedies Company, which became Richardson-Merrell Inc, and later Richardson Vicks Inc. Initially, Vicks struggled to sell outside the Greensboro area until Lunsford’s son, H. Smith, decided to concentrate only on the renamed VapoRub, the one unique and distinctive product of the 21.


Lunsford was active in Church activities (as elder to First Presbyterian). An editorial in the Greensboro Daily News August 22, 1919 said, “he never passed anyone on the street, young or old, black or white, without a nod and a smile.” He was particularly interested in the welfare of African-Americans. During World War II, a Liberty ship was christened the S.S. Lunsford Richardson at “special request of the leading Negro citizens of North Carolina to honor the memory of a white friend.” L. Richardson Memorial Hospital in Greensboro was renamed to honor him after receiving his donations for a modernization program, it originally served the black community.

Vick’s VapoRub, a Japanese mint oil extract called “menthol” mixed with camphor and eucalyptus oil in a petroleum jelly base, which vaporizes by body heat alone, and also safe on the skin , to this day is still doing  well.

The operation became Vick Chemical Company in 1911 and made increasing profits with its Vicks VapoRub cold remedy. The Company was managed over the following decades by Richardson’s sons H. Smith (1885-1972) and Lunsford, Jr. (1891-1953). After various mergers and acquisitions, it became Richardson-Vick, Inc., in 1980. In 1985 the Richardson family sold the company to Procter & Gamble Co.


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Panel Endorses Active Monitoring and Delay of Treatment for Low-Risk Prostate Cancer



Prostate cancer is the most common non-skin cancer in men in the US. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90% of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.


Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.


An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies-such as active surveillance-have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.


The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.


The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.


The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.


With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.


An updated version of the panel’s draft statement, which incorporates public comments received in an open conference session, is available online.

Tracheobronchial Transplantation with a Stem-Cell-Seeded Bioartificial Nanocomposite



Tracheal tumors can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. As a result, a study published online in The Lancet (24 November 2011) reported the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite.


The treated patient was a 36-year-old male patient who presented with recurrent primary cancer of the distal trachea and main bronchi. The patient was previously treated with debulking surgery and radiation therapy. After complete tumor resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 hours. Postoperative granulocyte colony-stimulating factor filgrastim (10 ug/kg) and epoetin beta (40,000 UI) were given over 14 days. The study also used flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses as outcome measures.


Results showed an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumor free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularized neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, mobilization of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodeling, and neovascularisation of the graft.


According to the authors, tailor-made bioartificial scaffolds can be used to replace complex airway defects, and that the bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.

Dietary Fiber, Whole Grains, and Risk of Colorectal Cancer



According to an article published online in the British Medical Journal (10 Nov 2011) a study was performed to investigate the association between intake of dietary fiber and whole grains and risk of colorectal cancer. The study was a systematic review and meta-analysis of prospective observational studies.


Twenty five prospective studies were included in the analysis. Results showed that the relative risk (RR) of developing colorectal cancer for 10g daily of total dietary fiber (16 studies) was 0.90, for fruit fiber (n=9) was 0.93, for vegetable fiber (n=9) was 0.98, for legume fiber (n=4) was 0.62, and for cereal fiber (n=8) was 0.90. The summary RR for an increment of three servings daily of whole grains (n=6) was 0.83 (for our American readers, 10g is equivalent to about 2.5 teaspoons).


According to the authors, a high intake of dietary fiber, in particular cereal fiber and whole grains, was associated with a reduced risk of colorectal cancer. The authors added that further studies should report more detailed results, including those for subtypes of fiber and be stratified by other risk factors to rule out residual confounding, as well as an assessment of the impact of measurement errors on the risk estimates is also warranted.

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


Drug Shortages


The shortage of life-saving and life-modulating drugs is major problem facing all of us. Drug shortages can occur for many reasons, including “poor public policies,” manufacturing and quality problems, delays, and discontinuations. FDA takes great efforts, within its legal authority, to address and prevent drug shortages. The agency works closely with manufacturers of drugs in short supply to communicate the issue and to help restore availability. FDA also works with other firms who manufacturer the same drug, asking them to increase production, if possible, in order to prevent or reduce the impact of a shortage.


Manufacturers are not required to report information, such as reasons for shortages or the expected duration of shortages. However, many companies voluntarily provide shortage information that FDA posts on its website. FDA encourages and appreciates all reporting of shortages by manufacturers. Shortage notifications and updates may be reported to FDA.


Perhaps we need a government regulation to assure that critical drugs are not just simply removed from the market for “business reasons.” With all the over-capacity and under-utilization of manufacturing plants as result of downsizing, why not create a “war on drug shortages” and create government sponsored program to assure that any critical drug that has become “short” due to “business decisions” is moved into production under a government license with guarantees. Not too different the way the government regulates utility companies and makes sure the “lights don’t go out.”

Dr. Berwick Departs CMS-Sad, Inevitable, & Dangerous


By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.


The abrupt and prematurely ended tenure of Dr. Donald Berwick as head of the Center for Medicare & Medicaid Services (CMS) promised from the beginning to be tumultuous. When nominated, he seemed the ideal candidate, manifestly expert, demonstrably passionate, and with broad and deep experience. Ironically, it was in large measure these seemingly positive qualities that made his appointment contentious.


Over the course of a long career in highly visible positions Dr. Berwick inevitably established a robust public record. He made statements about the limitations of health care resources and the related need for thoughtful and transparent allocation decisions, as well as positive comments about the National Health Service and NICE (National Institute for Health & Clinical Excellence) in the UK. In the context of the heated rhetoric during debates surrounding the Affordable Care Act, Berwick’s words became grist for the opponents of his nomination to lead the CMS. Ultimately, his nomination was opposed by Congressional Republicans and, with Senate confirmation deemed unrealistic, his tenure was enabled by a Presidential decision to circumvent the standard confirmation process through a recess appointment. While this efficiently and immediately placed Dr. Berwick in the job, it also virtually assured that ultimate confirmation for a permanent appointment would prove impossible. Thus, from the beginning, Dr. Berwick, the Administration, health professionals, and the public (that’s all of us as potential patients) had to assume that his tenure would be short. He was a “lame-duck” leader from the start.


Since he just stepped down, there are insufficient data and there has been insufficient time for a post-mortem on Dr. Berwick’s brief tenure. However, as a consequence of this sad situation, some general observations are in order.


Dr. Berwick seems to be precisely the sort of individual we would like to see in public service: thoughtful, expert, experienced, independent, and widely respected with an established record of achievement. People with these characteristics are also likely, almost certainly, to have taken controversial positions, and in Dr. Berwick’s fate we confront a profound and dangerous dilemma in our public life; specifically, our need for individuals of stature to participate in public life is increasingly at odds with our contentious politics. As our problems mount in multiple arenas, we desperately need the wisdom of men and women of expertise, independence and courage.


To the extent that we preclude their ability to serve, as has happened with Dr. Berwick, we place ourselves at peril.