By Kirsty Barnes,

While India, the Asia-Pacific, Eastern Europe and Latin America are all gaining recognition as potential new hot spots, South Africa remains ‘underutilised as a clinical trial destination,’ according to a prominent industry figure.

South Africa’s “distant” proximity to the US, along with an accompanying ignorance and lack of perception about what the country has to offer in terms of clinical research are partly to blame for this, Catherine Lund, vice chapter head of the South African arm of the Associate of Clinical Research Professionals (ACRP) and founder of South Africa-based CRO OnQ Consulting, told Outsourcing-Pharma.com.

The country’s “cumbersome” regulatory environment has also been a deterrent to some people considering including South Africa in a global study. Currently it takes 12-14 weeks from trial submission to approval, compared to around a month for most western countries, said Lund.

“On the surface, this can turn potential sponsors off,” she said. However, in terms of its competition with other emerging markets and offshore locations, South Africa does not seem to be faring so badly…

In Latin American countries, regulatory timelines are considerably longer - it often takes 9 to 12 months to have a site up and running - while the Japanese clinical trial environment has typically been less than welcoming, burdened by red tape and language barriers, although the government is in the process of pushing through a series of proposed reforms to change this.

On the other hand, Russia is planning to implement new, stricter legislations that will more closely regulate the country’s clinical trials industry, including making it a requirement that in order to run a clinical trial, a site will now be required to obtain permission for each individual trial it plans to conduct, as opposed to the current system where a site is just required to undergo an accreditation procedure that would cover it for all future studies at its medical facilities.

Lund identified Eastern Europe and India as the main regions that South Africa is competing with in terms of attracting clinical business, but said that “Eastern Europe is getting more and more expensive, so South Africa has a cost advantage there.”

However, India, which has historically also had a very cumbersome regulatory process, has really lifted its game over the past year and now poses more of a competitive threat, with a low cost base and now a short regulatory turnaround time.

There have been lots of positive regulatory developments in the country since January, one of which slashed the turnaround time for a company to obtain permission from the regulator to run a clinical trial from between 10 and 16 weeks, to between two and four weeks for trials in category A, and between six and eight weeks for those in category B.

Category A trials are those that already have the protocol approved in one of a number of countries on an approved list. The remainder are placed in category B.

Lund did point out, however, that some questions have been raised over various issues of quality in India, including by publications such as Centerwatch, and this is where she believes South Africa may have an advantage.

South Africa, has a very stringent regulatory system aimed at protecting its citizens and this year has been strengthening existing laws to improve the quality and transparency of trials human research, including making it compulsory to publish both positive and negative results of trials.

The country first established a national clinical trials register in 2005, where once a trial is approved by the ethics committee, the details are automatically registered. It was one of the first countries in the world to have such a system.

The country’s National Health Research Ethics Council is also in the process of setting up an accreditation process to standardise the processes of the over 30 ethics committees in operation.

“Therefore, if we [South Africa] can streamline our regulatory process then we will reduce a major obstacle,” Lund said.

“Currently the South African regulators are under-resourced and communication is a problem.”

However, a task team comprised of representatives from the industry, government and trade associations are all working together to make positive changes, and it is hoped that new reforms will be implemented next year, she said.

In the meantime, Lund believes that South Africa’s advantages lie in its patient population of nearly 50m, many of which are treatment naïve and have a wide diversity in genetic backgrounds.

“Because of this we often recruit for trials quite quickly compared to other parts of the world.” The country is also a popular choice for sponsors who need a ‘rescue site,’ for rapid recruitment if another one elsewhere in the world has failed to recruit enough patients in time, she said.

Furthermore, the country is also growing as a location to conduct seasonal studies, as it is in a different hemisphere to the US and Europe.

In addition, Lund indicated that South Africa is also a perfect launching pad for the increasing numbers of sponsors who are looking to gain exposure to African patients in order to broaden their overall clinical trial patient base to give the study a more global picture, as well as to run trials for new drugs to treat diseases that are highly prevalent in this region, such as HIV.

Originally posted in www.in-pharmatechnologist.com

The National Institutes of Health (NIH) announced an expanded ClinicalTrials.gov database. The database will accept basic results information, in addition to trial registrations. Due to growing public interest and a desire for improved access to clinical trial information and greater transparency in clinical research, Congress enacted Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA, Public Law 110-85, section 801). In response to this new legislative mandate, those responsible for conducting clinical trials will submit data after the trial is completed. The enhanced database will provide summary results statistics for a broad range of trials of drugs, medical devices and biological products that have been approved by the Food and Drug Administration. Patient-identifiable information will not be included.

“Providing scientists, physicians, and the public with results information could go a long way toward improving safety,” said Director Elias Zerhouni, M.D.

Clinical trials are research studies that test how well new medical approaches work in people. Each study answers specific scientific questions and tries to find better ways to prevent, screen for, diagnose, or treat a disease. Since 2000, ClinicalTrials.gov, the largest single registry of clinical trials, has provided patients, families and members of the public with easy access to information about a trial’s purpose, who may participate, locations, and phone numbers for more details. This Web site currently has information on nearly 62,000 ongoing and completed trials sponsored by the U.S. Federal government, pharmaceutical industry, academic, and international organizations with locations in all 50 States and in 157 countries.

“In time, the results database will be a powerful tool for researchers and health care consumers alike, and will have untold benefits for the public health too.” said Donald A.B. Lindberg, M.D., Director of the NIH’s National Library of Medicine which developed and administers the new results database.

Results information will be integrated into the clinical trial records that can be reached at http://clinicaltrials.gov/, and through its consumer health information service, MedlinePlus, at http://medlineplus.gov. MedlinePlus has extensive links to information about 750 diseases and health conditions, much of it from the NIH Institutes and Centers.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Located in Bethesda, Md., the National Library of Medicine is the world’s largest library of the health sciences. For more information, visit the Web site at http://www.nlm.nih.gov.

*Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA, Public Law 110-85, section 801) enacted on September 27, 2007, expanded the scope of trials and information required to be submitted to Clinical Trials.gov and required the submission of results data. This system builds on the existing ClinicalTrials.gov Protocol Registration System and allows sponsors and principal investigators to clinical trials to submit “basic results” summary data necessary to satisfy statutory requirements. Submission will be publicly posted on ClinicalTrials.gov

National Institutes of Health

Complexities of Clinical Trials- 34 min - Aug 20, 2004
Transverse Myelitis Association - http://www.myelitis.org/rnds2004/

2004 Rare Neuroimmunologic Disorders Symposium Complexities of Clinical Trials J. McArthur, MBBS, MPH

ImmunoVaccine Technologies’ DepoVax(TM) Shows Positive Results For Cancer And Infectious Diseases

ImmunoVaccine Technologies’ (IVT) patented depot vaccine formulation, DepoVax(TM) is showing positive pre-clinical results, with single-dose efficacy achieved in therapeutic cancer and several infectious disease vaccine models. The results of this research will be presented October 4th at the Ehrlich II conference in Germany. Collaborators from the University of Miami will also be reporting on the capabilities of IVT’s depot formulations for delivery of DNA and SiRNA in vivo.

DepoVax(TM) provides a unique single-dose capability, and is based on a novel approach to the use of liposomes, which encapsulate a target antigen and adjuvant. The vaccine formulation also relies on a hydrophobic oil carrier. The result is a depot effect that significantly enhances vaccine induced cell-mediated and humoral immunity.

The efficacy of a single dose of a DepoVax(TM) formulation was shown using a Human Papilloma Virus (HPV) associated cervical cancer model. In the therapeutic C3 tumor challenge model, DepoVax(TM) eliminated 100% of established cancerous tumors after a single dose. In contrast, tumors remained intact when treated with a placebo vaccine. The effect of the vaccine is linked to the activation of a potent and specific cellular immune response.

Read more ….

MedicalNewsToday.com

GeoVax Labs, Inc. (OTC Bulletin Board: GOVX), an Atlanta based, publicly traded biopharmaceutical company specializing in the prevention and treatment of infectious diseases, provided an operational update on the company’s progress towards entering Phase 2 preventative human clinical trial testing and plans to proceed into therapeutic human trials with its AIDS vaccine. Five successful human trials evaluating GeoVax AIDS vaccines have previously been reported.

Planned Phase 2 Human Clinical Trial for Prevention of AIDS

The Company’s Phase 2 trial, conducted by the U.S. National Institutes of Health (NIH) supported HIV Vaccine Trials Network (HVTN), will involve 225 healthy volunteers from the United States and South America, and will further evaluate the safety and immunogenicity of the GeoVax preventative vaccine (vaccine administered prior to infection with the HIV virus). In Phase 1 trials, both 1/10th dose and full dose of the GeoVax vaccine elicited anti-HIV T-cells, whereas the full dose was required to elicit good frequencies of antibody to the HIV Envelope glycoprotein. The larger Phase 2 human trial will broaden the base of safety and immunogenicity data for the full dose of the GeoVax AIDS vaccine with a view to protecting recipients from developing AIDS should they be exposed to the virus. The planned Phase 2 human clinical trial is currently scheduled to start early this fall, subject to FDA approval.

Preclinical Data for Use of Vaccine Technology as an AIDS Therapeutic Human Clinical Trials in Planning Stages GeoVax also announced summary data from a pilot study on therapeutic vaccination in simian immunodeficiency virus (SIV) infected non-human primates with the SIV prototype for the GeoVax AIDS vaccine. In this small pilot study, conducted by Dr. Amara at Emory University, two non-human primates were infected with SIV. At 12 weeks post SIV infection, conventional anti-viral drug therapy was given to the primates to reduce the viral RNA infection levels to very low levels creating a non progressor status for the primate. Then the SIV prototype vaccine for the GeoVax AIDS vaccine was administered. Six weeks following the final vaccination, anti-viral drug treatment was stopped and the animals were monitored to determine whether the vaccine could control the SIV infection during the absence of the drugs.

The outstanding results from the study revealed the vaccine controlling the infection in the absence of drugs. In one primate, the reduction in viral levels over pre-drug treatment and vaccination levels was 1000 times. In the other, the reductions in viral levels were 100 times. The excellent control of the virus infection in the absence of drug treatment was associated with the vaccine raising the types of CD4 and CD8 T cells that are found in the rare individuals who spontaneously control their HIV infections.

Based on these excellent results, planning for a therapeutic trial in infected and drug treated humans has been initiated. The intent of therapeutic vaccination is for the vaccine to “control” HIV virus levels in infected individuals to very low levels thus blocking the development of AIDS. Successful therapeutic AIDS vaccination programs with GeoVax vaccines would lead to reduction in the use of costly anti-HIV medications and their often harmful side effects.

Dr. Harriet Robinson, GeoVax Co-founder and Senior V.P. of Research and Development, commented, “I had not anticipated the extent of vaccine control that was achieved in the already infected non-human primates. These are highly promising results that need to be extended into infected humans to see if the vaccine can be used to reduce the need for taking drugs. The results also warrant more extended studies in already infected non-human primates to explore parameters that both limit and enhance the ability for a vaccine to displace the need for drugs.”

Dr. Robert McNally, CEO and President of GeoVax Labs, Inc., emphasized, “It is noteworthy to mention that the GeoVax AIDS vaccines being tested in the preclinical therapeutic trial is the same basic vaccine administered in the Company’s human trials testing for a preventative use of the vaccine, vaccinating people before infection to prevent the development of AIDS should they become infected. Thus, a “one for two” vaccine could be a breakthrough solution for the company and the world, saving millions of dollars in redundant development costs and years of testing time by utilizing safety data already achieved in Phase 1 preventative human trials. More important, time to market could be significantly reduced, saving lives much sooner than otherwise.”

Further, GeoVax’s management is pleased to report that the company is currently engaged in negotiations with a NIH sponsored trial network to administer, conduct and co-sponsor GeoVax’s Therapeutic human trial program. Management expects to receive approval for undertaking formal protocol development in the near future and will report more detailed plans accordingly.

“From an operational standpoint, we are very pleased with the overall progress of the company,” stated Dr. Robert McNally. “Progress with ongoing preventative vaccine trials and now the potential to address therapeutic use of the vaccine gives GeoVax an expanding role in the fight to control AIDS.”

About GeoVax Labs, Inc.

GeoVax Labs, Inc. is a biotechnology company, established to develop, manufacture, license and commercialize human vaccines for diseases caused by HIV-1 (Human Immunodeficiency Virus) and other infectious agents. GeoVax’s AIDS vaccine technology is the subject of 20 issued or filed patent applications. GeoVax AIDS vaccines are designed for use in uninfected people to prevent Acquired Immunodeficiency Disease (AIDS), caused by the virus known as HIV-1, should the person ever become infected. GeoVax AIDS vaccines also may be effective as therapeutics, treatment of people already infected with AIDS virus.

GeoVax’s core AIDS vaccine technologies were developed by Dr. Harriet Robinson, Senior V.P. of Research and Development, through a collaboration of colleagues at Emory University’s Vaccine Center, the National Institutes of Health (NIH), The Centers for Disease Control and Prevention (CDC) and GeoVax.

GeoVax AIDS vaccines have moved forward in human clinical trials conducted by the HIV Vaccine Trials Network (HVTN) based in Seattle, Washington. The HVTN, funded through a cooperative agreement with the National Institutes of Health (NIH), is the largest worldwide clinical trials program dedicated to the development and testing of AIDS vaccines. Preclinical work enabling evaluation of GeoVax DNA and MVA vaccines was funded and supported by NIAID, which provided additional support to GeoVax AIDS vaccine development program with a $15 million IPCAVD grant awarded in late 2007.

Safe Harbor Statement: All statements in this news release, not statements of historical fact, are forward-looking statements. These statements are based on expectations and assumptions on the date of this press release and are subject to numerous risks and uncertainties which could cause actual results to differ materially from those described in the forward-looking statements. Risks and uncertainties include, but are not limited to, whether: GeoVax can develop and manufacture these vaccines with the desired characteristics in a timely manner, GeoVax’s vaccines will be safe for human use, GeoVax’s vaccines will effectively prevent AIDS in humans, vaccines will receive regulatory approvals necessary to be licensed and marketed, GeoVax raises required capital to complete vaccine development, there is development of competitive products that may be more effective or easier to use than GeoVax’s products, and other factors over which GeoVax has no control. GeoVax assumes no obligation to update these forward-looking statements, and does not intend to do so. Certain matters discussed in this news release are forward-looking statements involving certain risks and uncertainties including, without limitation, risks detailed in the Company’s Securities and Exchange Commission filings and reports.

GeoVax Labs, Inc.
http://www.geovax.com

A Paradigm Shift in Pharmaceutical Clinical Trials - 6 min - Jul 13, 2007

Taren Grom, Editor of PharmaVOICE magazine talks with Ira Spector, Vice Chief of Clinical Operations at Wyeth, about improving clinical trials in the pharmaceutical industry. Part of the PharmaVOICE Webcast Network.

Resolvyx Pharmaceuticals, Inc., the leading resolvin therapeutics company, today announced that a research team led by a Resolvyx scientific advisor and a company co-founder has demonstrated that the resolvin E1 (RvE1) effectively suppresses IL-23 and IL-17, two key inflammatory mediators of chronic inflammatory disease, in a preclinical model of asthma. RvE1 is the active ingredient in RX-10001, one of Resolvyx’s leading clinical candidates. The paper, titled “Resolvin E1 regulates interleukin 23, interferon-? and lipoxin A4 to promote the resolution of allergic airway inflammation,” published in the journal Nature Immunology.

“This study demonstrates that RvE1 potently suppresses IL-23 and IL-17, which are critical in regulating airway inflammation in chronic asthma,” said Bruce D. Levy, M.D., lead author of the study, scientific advisor to Resolvyx and Associate Professor of Medicine at the Department of Internal Medicine Pulmonary and Critical Care Medicine Division, Brigham and Women’s Hospital. “As the IL-23/IL-17 pathway has been increasingly linked to chronic inflammation, tissue remodeling, pathological neovascularization and bone loss, these results have implications for the therapeutic potential of resolvins in a range of human diseases.”

The research team evaluated RX-10001 (RvE1) in a well established mouse model of asthma and showed that RX-10001 (RvE1), when administered at the peak of inflammation, significantly suppressed airway inflammation and prevented lung hyperreactivity. The levels of IL-17 and IL-23 were reduced by 70% and 60%, respectively, contributing to a greater than 80% reduction in infiltrating leukocytes including eosinophils, which are a major driver of the allergic airway hyper-responsiveness.

“The finding that RX-10001 suppresses IL-23 and IL-17 suggests that resolvins can potentially treat not only asthma but also inflammatory bowel disease, rheumatoid arthritis, atherosclerosis and other diseases,” said Charles Serhan, Ph.D., co-author of the study, co-founder of Resolvyx and Director of the Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women’s Hospital. “Given their broad potential to treat human disease, it is very exciting that Resolvyx is advancing resolvin drug candidates into clinical trials in the coming months.”

Resolvyx also has conducted preclinical studies with RX-10001 (RvE1) in asthma and other systemic inflammatory diseases. Resolvyx has announced plans to initiate human clinical trials for RX-10001 in the first half of 2009.

About Resolvins

Resolvins are a recently discovered family of naturally-occurring, small molecule lipid mediators that can be targeted to treat a wide range of diseases. In particular, resolvins act to protect healthy tissue during an immuno-inflammatory response to infection, injury or other environmental challenge, and then act to resolve inflammation and promote healing after the insult has passed. Resolvins are shown to be highly potent and efficacious in pre-clinical models of asthma, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, dry eye and retinal disease, among others.

Resolvins are potential drug candidates to treat a broad range of acute and chronic diseases caused by a failure to resolve the inflammatory response and restore immune homeostasis. Such diseases include auto-immune diseases (like Crohn’s disease, psoriasis and rheumatoid arthritis), allergic diseases (like asthma) and chronic inflammatory diseases (like atherosclerosis, degenerative retinal diseases, chronic dry eye and Alzheimer’s disease). Resolvins offer an entirely novel biological approach to treating significant inflammatory diseases, with a decreased potential for immuno-suppression.

About Resolvyx Pharmaceuticals

Resolvyx Pharmaceuticals is a privately-held biopharmaceutical company dedicated to the discovery, development and commercialization of resolvins, a novel class of therapies to treat inflammatory diseases and their complications. Resolvyx’s drug R&D programs are focused on characterizing and developing resolvin-based compounds. With its experienced management team, world-class scientists and leading investors, Resolvyx is well-positioned to capitalize on its extensive portfolio of more than 55 patents and applications. The company’s headquarters are in Bedford, Massachusetts.

http://www.resolvyx.com.

Contract research organizations (CROs) hope to obtain an edge in the highly competitive healthcare industry by using technology to shorten project times, improve data quality, and thus, differentiate services. As clinical trials globalize, sponsor companies and CROs increasingly look for tools that will help them simultaneously view, manage and discuss these trials across multiple sites. New analysis from Frost & Sullivan, U.S. Clinical Trial Management Systems Markets, finds that market earned revenues of $237.6 million in 2007 and estimates to grow at a compound annual growth rate of 14.5 percent between 2007 and 2014.

Clinical trial management systems (CTMS) have emerged as the best-suited solution to provide this competitive advantage to CROs. These tools will also enable the CRO to collaborate with clients and contribute key information that enhances data quality.

CTMS employs intelligent applications and access to clean data. This helps users improve overall efficiency and shortens trial timelines, lowering overall cost through better utilization of resources. In addition, the systems use automated data checks to ensure reliability of data, thereby reducing the need for expensive back-end queries and reconciliation.

“CTMS has the potential to enable decision making and improve patient safety protection,” notes Frost & Sullivan Research Analyst Barath Shankar S. “The success of implementing electronic data capture (EDC) solutions is a strong driver for the implementation of CTMS solutions.”

CROs are under increased pressure to explain the rapid rise in the number of post-marketing adverse events. This drives them to invest in tools that capture and manage trial data more effectively.

While this trend likely pleases vendors of the highly dynamic CMTS market, participants must also prepare for the eventual maturing of the market. Henceforth, system vendors will increasingly deal directly with CROs, which will be primary decision makers while choosing the vendor.

Additionally, CROs will be conscientious while selecting a CMTS vendor to conduct business with, since sponsors will prefer CROs that function as a one-stop shop and offer integrated solutions for running and managing trials.

“Meanwhile, the cost and resource implications for smaller CROs and BioPharma companies in CTMS implementation are significant,” notes Shankar. “It is important to account for hidden costs while calculating the total cost of deployment and operation of CTMS solutions.”

U.S. Clinical Trial Management Systems Markets is part of the Pharmaceutical & Clinical Diagnostics Growth Partnership Service program, which also includes research in the following markets: global pharmaceutical contract manufacturing markets, global CRO spending trends, and U.S. drug discovery CRO markets. All research services included in subscriptions provide detailed market opportunities and industry trends that have been evaluated following extensive interviews with market participants. Interviews with the press are available.

Frost & Sullivan, the Growth Partnership Company, partners with clients to accelerate their growth. The company’s TEAM Research, Growth Consulting and Growth Team Membership empower clients to create a growth-focused culture that generates, evaluates and implements effective growth strategies. Frost & Sullivan employs over 45 years of experience in partnering with Global 1000 companies, emerging businesses and the investment community from more than 30 offices on six continents.

Frost & Sullivan

Medicalnewstoday.com

Oramed Pharmaceuticals, Inc. (OTCBB: ORMP.OB), a developer of oral delivery systems, announced successful results from the clinical trial of its oral insulin capsule, ORMD 0801. The trial demonstrated that the product had a good safety profile and well tolerated and effective in lowering blood glucose levels in patients with type 2 diabetes.

The study was conducted at Hadassah University Medical Center in Jerusalem and was a continuation of the successful Phase 1B trials that Oramed completed earlier this year.

This trial was the first to expose patients with type 2 diabetes to ORMD 0801 and its primary goals were to assess the safety, tolerability and pharmcodynamic effects in these patients.

ORMD 0801 was well tolerated by all patients and had a good safety profile; no serious adverse events were encountered throughout the study. In 6 of the 9 subjects analyzed, statistically significant reductions in glucose as well as C-peptide were observed.

Read more ….

MedicalNewsToday.com

Thyroid cancer that has spread to distant sites has a poor prognosis, but an experimental drug that inhibits tumor blood vessel formation can slow disease progression in some patients, a research team led by investigators from The University of Texas M. D. Anderson Cancer Center reports in the July 3rd edition of The New England Journal of Medicine.

The investigational drug, motesanib diphosphate, is a VEGF inhibitor, a biologic agent that targets receptors on a protein known as vascular endothelial growth factor (VEGF). VEGF is instrumental in angiogenesis (formation of new blood vessels), a process that allows tumors to grow and spread.

Study lead author Steven I. Sherman, M.D., chair and professor of M. D. Anderson’s Department of Endocrine Neoplasia and Hormonal Disorders, noted strong evidence that VEGF receptors play an important role in metastatic thyroid cancer, a disease with few treatment options.

Read more ….

MedicalNewsToday.com

BioNumerik Pharmaceuticals, Inc. (”BioNumerik”) announced that patients with adenocarcinoma (the most frequently occurring form of lung cancer) participating in a Phase II clinical trial of Tavocept(TM) showed a survival increase of approximately 198 days (6.5 months). The trial observations included an approximate 40% reduction in mortality for adenocarcinoma patients receiving Tavocept. The percentage of adenocarcinoma patients in the Tavocept group who were alive after 12 months (One-year survival) was 58% compared to 37% for adenocarcinoma patients in the chemotherapy only group. The median survival time for all non-small cell lung cancer (NSCLC) patients in the trial showed an increase of approximately one month for patients receiving Tavocept. This is the second Tavocept clinical trial where this pattern of survival increase has been observed. Tavocept is an investigational new drug with potential for oncology and non-oncology indications that was originated and developed by BioNumerik.

The randomized Phase II clinical trial (the “U.S. Tavocept Trial”) was performed at multiple sites in the U.S. and involved 151 patients with advanced NSCLC who received the chemotherapy drugs docetaxel (sold under the brand name Taxotere(R)) and cisplatin every two weeks. Approximately half of the patients received Tavocept along with chemotherapy, while the other half received chemotherapy alone.

Read more ….

MedicalNewsToday.com

High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences. The researchers traced ascorbate’s anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors. Normal cells were unaffected.

Natural physiologic controls precisely regulate the amount of ascorbate absorbed by the body when it is taken orally. “When you eat foods containing more than 200 milligrams of vitamin C a day–for example, 2 oranges and a serving of broccoli–your body prevents blood levels of ascorbate from exceeding a narrow range,” says Mark Levine, M.D., the study’s lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH. To bypass these normal controls, NIH scientists injected ascorbate into the veins or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatic tumors. By doing so, they were able to deliver high doses of ascorbate, up to 4 grams per kilogram of body weight daily. “At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment,” said Levine.

Read more ….

MedicalNewsToday.com

Staffing Challenges in Clinical Research - 6 min - Originally posted on Jul 13, 2007

Taren Grom, Editor of PharmaVOICE magazine talks with Micheal Hliniak, CEO of InVentiv Clinical, about staffing challenges in the outsourcing arena. Part of the PharmaVOICE Webcast Network.

Tiny strands of genetic material called RNA - a chemical cousin of DNA - are emerging as major players in gene regulation, the process inside cells that drives all biology and that scientists seek to control in order to fight disease.

The idea that RNA (ribonucleic acid) is involved in activating and inhibiting genes is relatively new, and it has been unclear how RNA strands might regulate the process.

In a new study available online and in a future issue of Nature Structural and Molecular Biology, RNA experts at UT Southwestern Medical Center found that, contrary to established theories, RNA can interact with a non-gene region of DNA called a promoter region, a sequence of DNA occurring spatially in front of an actual gene. This promoter must be activated before a gene can be turned on.

“Our findings about the underlying mechanisms of RNA-activated gene expression reveal a new and unexpected target for potential drug development,” said Dr. David Corey, professor of pharmacology and biochemistry at UT Southwestern and one of the senior authors of the study.

Genes are segments of DNA housed in the nucleus of every cell, and they carry instructions for making proteins. Faulty or mutated genes lead to malfunctioning, missing or overabundant proteins, and any of those conditions can result in disease. Scientists seek to understand the mechanisms by which genes are activated, or expressed, and turned off in order to get a clearer picture of basic cell biology and also to develop medical therapies that affect gene expression.

In previous studies, Dr. Corey and Dr. Bethany Janowski, assistant professor of pharmacology at UT Southwestern and a senior author of the current study, have shown that tiny strands of RNA can be used to activate certain genes in cultured cancer cells. Using strands of RNA that they manufactured in the lab, the researchers showed that the strands regulate gene expression by somehow perturbing a delicate mixture of proteins that surround DNA and control whether or not genes are activated.

Until now, however, it was not clear exactly how the synthetic RNA strands affected that mix of regulating proteins.

In the current study, also carried out in cancer cell cultures, the UT Southwestern research team discovered an unexpected target for the manufactured RNA. The RNA did not home in on the gene itself, but rather on another type of RNA produced by the cell, a so-called noncoding RNA transcript. This type of RNA is found in association with the promoter regions that occur in front of the gene. Promoter regions, when activated, act essentially as a “start” command for turning on genes.

The researchers found that their man-made RNA strand bound to the RNA transcript, which then recruited certain proteins to form an RNA-protein complex. The whole complex then bound to the promoter region, an action that could then either activate or inhibit gene expression.

“Involvement of RNA at a gene promoter is a new concept, potentially a big new concept,” Dr. Janowski said. “Interactions at gene promoters are critical for understanding disease, and our results bring a new dimension to understanding how genes can be regulated.”

Until recently, many scientists believed that proteins alone control gene expression at promoters, but Drs. Corey and Janowski’s results suggest that this assumption is not necessarily true.

“By demonstrating how small RNAs can be used to recruit proteins to gene promoters, we have provided further evidence that this phenomenon should be in the mainstream of science,” Dr. Corey said.

Although using synthetic RNA to regulate gene expression and possibly treat disease in humans is still in the future, Dr. Corey noted that the type of man-made RNA molecules employed by the UT Southwestern team are already being used in human clinical trials, so progress toward the development of gene-regulating drugs could move quickly.

Other researchers from UT Southwestern involved in the research were lead author and student research assistant Jacob Schwartz; student research assistant Scott Younger; and research associate Ngoc-Bich Nguyen. Researchers from the University of Western Ontario and ISIS Pharmaceuticals also participated.

The research was supported by the National Institutes of Health and the Welch Foundation.

MDS Pharma Services, a leading provider of innovative drug discovery and development solutions, has launched the next generation of its proprietary ClinQuick(R) electronic system for Phase I study set-up, data capture, project tracking and personnel credential management. Aimed at improving client service, the new version of the ClinQuick(R) system extends a 15-year legacy of technical leadership in early clinical research. System enhancements include a more user-friendly interface, improved menu navigation and a more robust data platform. This new platform will enable faster and more flexible reporting and will ultimately allow clients to access their data via the internet.

“Since its implementation in 1993, ClinQuick(R) has been used successfully in more than 3,000 Phase I studies involving nearly 100,000 participants,” said MDS Pharma Services President David Spaight. “Our investment to enhance the ClinQuick(R) system builds on that legacy of success and will allow us to meet growing client demand for early clinical research services while maintaining our leadership position in Phase I. This next-generation ClinQuick(R) system will further improve our ability to deliver high quality Phase I services on time.”

About ClinQuick(R)

Designed and built by MDS Pharma Services for use in its Phase I clinical research centers, the fully integrated ClinQuick(R) system facilitates rapid data cleansing and client monitoring for seamless operation of both single and multi-site studies. ClinQuick(R) accelerates timelines, enables accurate direct data acquisition, and reduces costs by a third compared to traditional paper case report forms (CRFs) - the forms used by clients to collect and document data from each participating clinical research site. The system is fully CFR Part 11 compliant and can be used for study management and electronic data capture (EDC), either alone or in conjunction with a client-provided EDC system or paper CRFs. MDS Pharma Services offers one of the world’s largest capacities for conducting early-phase clinical studies, with some 1,100 beds in five state-of-the-art clinical research facilities in North America and Europe.

About MDS Pharma Services

MDS Pharma Services is committed to delivering quality service on time. We offer a full spectrum of resources to meet the drug discovery and development needs of the pharmaceutical and biotechnology industries. With numerous facilities strategically located around the world, we apply advanced scientific and technological expertise throughout the drug discovery and development process - from lead optimization, pre-IND research, early clinical research (bioequivalence, phases I-IIa) and bioanalysis through to global clinical development (phases IIb-IV), central lab and centralized cardiac services. For more information, visit our website at http://www.mdsps.com.

MDS Pharma Services is a business unit of MDS Inc. (TSX: MDS; NYSE: MDZ), a global life sciences company that provides market-leading products and services that our customers need for the development of drugs and diagnosis and treatment of disease. We are a leading global provider of pharmaceutical contract research, medical isotopes for molecular imaging, radiotherapeutics, and analytical instruments. MDS has more than 5,500 highly skilled people in 29 countries.

MDS Pharma Services
http://www.mdsps.com

The newest version of GE’s featured MUSE data management system incorporates upgrades in information technology, ECG management processes and clinical report editing in an all-digital environment for truly paperless workflow. “The MUSE version 7. 1 offers new benefits including additional options that enhance clinical workflows and improved IT connectivity,” said Dr. Matthias Weber, cardiologist and vice president of GE Healthcare’s Diagnostic Cardiology business. “The system is intended to better meet the needs for accessing comprehensive ECG data across the enterprise.”

Clinical Benefits

MUSE v7.1 provides high-fidelity digital access to resting ECG, Stress and Holter tests, allowing the clinician to review and edit studies on-line, from the comfort of home, anytime night or day. Clinical workflow is enhanced through the use of new display formats, magnification and measurement tools and statement editing capabilities. GE has added further measurement options, meeting the needs of pediatric cardiologists and those in other specialty areas. GE’s innovative Marquette® Serial Comparison program makes algorithmic comparative analysis available, on-demand. In addition, a number of IT capabilities are available to provide clinicians access to important patient data both inside and outside of the workplace.

Information Technology Benefits

Information Technology (IT) highlights include both a SQL 2005 relational database and a Windows Server 2003 operating system and is available as a software-only offering. THE MUSE system offers extensive HL7 interfaces and web integration with most major vendor EMR systems. A dedicated team is available to assist you during your implementation and integration needs. Additionally, the MUSE system provides an end-to-end workflow solution through optional wireless or LAN networking to the MAC5500 and 3500 electrocardiographs. Utilizing the hospital infrastructure for connectivity, along with the MUSE HL7 interface, the user can download patient demographic information and orders directly to the electrocardiograph.

Pharmaceutical Clinical Trials

The MUSE system has long been an important tool in addressing the unique challenges of pharmaceutical clinical trials. The recent MUSE v7 improvements include an Interval Editor option, with capabilities for ICH E-14 “thorough QT study” criteria. It also includes 21CFR Part 11 compliance aids and extensive XML export capabilities to assist in creating a compliant, readily auditable environment for submitting results to the FDA without a cumbersome certification process.

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Our expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, performance improvement, drug discovery, and biopharmaceutical manufacturing technologies is helping clinicians around the world re-imagine new ways to predict, diagnose, inform, treat and monitor disease, so patients can live their lives to the fullest.

GE Healthcare’s broad range of products and services enable healthcare providers to better diagnose and treat cancer, heart disease, neurological diseases and other conditions earlier. Our vision for the future is to enable a new “early health” model of care focused on earlier diagnosis, pre-symptomatic disease detection and disease prevention. Headquartered in the United Kingdom, GE Healthcare is a $17 billion unit of General Electric Company (NYSE: GE). Worldwide, GE Healthcare employs more than 46,000 people committed to serving healthcare professionals and their patients in more than 100 countries. For more information about GE Healthcare, visit our website at http://www.gehealthcare.com.

Pulmo BioTech Inc. (OTC Bulletin Board: PLMO.OB) has announced details of the methodology and purpose of its Phase I Human Trials with its PulmoBind Molecular Imaging technology for the diagnosis of Pulmonary Embolism and Pulmonary Hypertension.

The work will be carried out by the Pulmo BioTech subsidiary, PulmoScience Inc., and the title of the work is: “Phase I Study of the Use of PulmoBind for Molecular Imaging of the Pulmonary Circulation.”

The study will be a single center, Phase 1 safety and efficacy study of a single intravenous injection of PulmoBind in human subjects with no history of lung disease.

The Outcomes will be:

1. Safety — to determine pharmacokinetics and biodistribution of PulmoBind in humans and to perform dosimetric evaluation

2. Efficacy — to evaluate the ability of PulmoBind to allow lung perfusion imaging in humans

Pulmo BioTech expects this work to be completed by late summer 2008.

About Pulmo BioTech Inc.

Pulmo BioTech Inc. specializes in the development and marketing of medical technology and research. Our proven strengths combine extensive commercial experience and academic credentials. The principal staff members are acknowledged experts in their specialized fields, and work with a broad range of investment institutions. Pulmo BioTech’s mission is to utilize scientific imagination and drive, together with managerial and financial acumen, to bring innovative and profitable products to the marketplace to the benefit of all stock holders.

About PulmoScience Inc.

PulmoScience Inc. was established in 2006, and is currently developing a non-invasive Molecular Imaging technique for the diagnosis of Pulmonary Embolism, Pulmonary Hypertension and Lung Inflammatory diseases under the trade name PulmoBind.

The company was conceived within the Montreal Heart Institute “MHI” (a world renowned hospital and educational facility). Jointly owned by MHI subsidiary Innovacor as the technical and operational partner, Dr. Jocelyn Dupuis (the scientific director and originator of the PulmoBind Molecular Imaging technology), and by Pulmo BioTech Inc. as the funding partner, PulmoScience Inc. aims to develop this unique and exciting technology, to fund necessary trials, and to bring the products to market.

PulmoScience believes that the market for its product candidates is worth in excess of $500 million per annum and that, provided Regulatory Approval is achieved, the safety and efficacy of its products could allow it to dominate that market.

About PulmoBind

PulmoBind uses an intravenously delivered radionuclide tagged molecule which specifically bonds to the inner walls of the circulatory system in the lungs, and by the use of an external Gamma Camera allows an image of the integrity of the blood vessels throughout the lungs to be seen by a diagnostic clinician. PulmoScience is currently undertaking Regulatory Approval for Phase I Human Trials, and while subsequent results from additional tests might not corroborate the current results, PulmoScience believes that PulmoBind has the potential to dominate the market for the diagnosis of Pulmonary Embolism. In particular, this belief is driven by PulmoScience’s expectations of the improved safety and efficacy that PulmoBind will offer when compared to the current incumbent nuclear medicine based technology for the diagnosis of Pulmonary Embolism. In addition, early indications are that PulmoBind could be highly effective in the early stage diagnosis of Pulmonary Hypertension, a condition for which there is no current front line diagnostic test.

Forward Looking Statements

Forward-looking statements contained in this and other written and oral reports are made based on known events and circumstances at the time of release, and as such, are subject in the future to unforeseen uncertainties and risks. All statements regarding future performance, earnings projections, regulatory approval, events or developments are forward-looking statements. It is possible that the future performance of the company may differ materially from current expectations, depending on economic conditions and the uncertainty of regulatory approval. A change in economic conditions may have a particularly volatile effect on results. Among the other factors which may affect future performance are: competitive market conditions and resulting effects on sales and pricing; increases in raw-material costs that cannot be recovered in product pricing; and global economic factors, including difficulties entering new markets and general economic conditions such as inflation, interest rates and credit availability. The company makes these statements as of the date of this disclosure, and undertakes no obligation to update them.

Pulmo BioTech Inc.
http://www.pulmobiotech.com

Health Matters: Human Clinical Trials

There is a popular debate over the value and safety of human clinical trials, research studies that analyze medical information gathered from patient volunteers . Joe Ramsdell, M.D., UCSD School of Medicine, explains the role of the clinical trial in modern medicine. Series: “Health Matters” [2/2002] [Health and Medicine] [Show ID: 6096]

Complexities of Clinical Trials (34 minutes)

Courtesy of the Transverse Myelitis Association - http://www.myelitis.org/rnds2004/

2004 Rare Neuroimmunologic Disorders Symposium

Lecture by J. McArthur, MBBS, MPH

Can a blood test improve treatment outcomes for colorectal cancer patients? Recently published studies indicate that personalized chemotherapy dose management — measuring drug levels in patients’ blood and adjusting them for optimal dosing — can substantially reduce severe toxicity and improve efficacy in colorectal cancer.A Phase III randomized study of 208 colorectal cancer patients, by Erick Gamelin, M.D., Ph.D. et. al., was published in the May 1 issue of the Journal of Clinical Oncology (JCO). It found that metastatic colorectal cancer patients whose dose of 5-fluorouracil (5-FU) was personalized based on results of regular blood tests experienced reduced severe toxicities and nearly doubled response rates compared to patients who received standard 5-FU dosing based on body surface area. Additionally, patients who received personalized dosing experienced a 48 percent relative improvement in survival at two years. 5-FU is the cornerstone chemotherapy in most treatment regimens for this type of cancer.

The current standard-of-care in dosing 5-FU is based on body surface area (BSA) and is calculated using patients’ height and weight. In the JCO study, personalized dosing was based on blood tests to measure the actual level of the drug. The study demonstrated that only 25 percent of colorectal cancer patients achieved optimal chemotherapy blood levels when dosed by BSA. Seventeen percent of the BSA-dosed patients received toxic levels of the drug, while 58 percent were under-dosed.

The JCO study, “Individual 5-fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: Results of a multicenter randomized trial of patients with metastatic colorectal cancer,” evaluated patients being treated with 5-FU in combination with leucovorin. Half of the patients were dosed with 5-FU based on BSA. The other half were initially dosed based on BSA, with subsequent cycle doses adjusted based on blood tests that measured the actual concentration of chemotherapy in the patients’ blood plasma. The primary endpoint was tumor response; the secondary endpoint was treatment tolerance.

The JCO study concluded that:

– Response rates were nearly doubled in the dose adjusted group versus the BSA group (33.6 percent versus 18.3 percent) with statistical significance

– Overall survival at two years among patients with personalized 5-FU dose management improved by 48 percent with an improved median survival of 22 months versus 16 months in the BSA arm. The survival data was leaning towards significance

– Grade III/IV 5-FU related toxicities were found to be significantly lower in patients with personalized dose adjustment

– 58 percent of patients were found to be under-dosed (sub-therapeutic and less effective drug levels) and had their doses adjusted upwards

– 17 percent were found to be over-dosed (increasing the risk of severe side effects) and had their doses adjusted downward

Dr. Gamelin, director of the Paul Papin Cancer Center in Angers, France, stated, “Pharmacokinetically-guided or personalized 5-FU dose management is the standard-of-care at our cancer center. We routinely test the level of 5-FU in the blood of our colorectal cancer patients and adjust their doses to achieve optimal drug concentration. Clinical studies conducted over the past 20 years have demonstrated that there is significant variability in 5-FU blood levels when patients are dosed by BSA, the prevailing practice.”

“Our Phase III study demonstrates that the majority of patients are either over-dosed or in most cases, under-dosed. Personalized 5-FU dosing allows us to substantially reduce severe toxicity while improving patient quality of life and treatment outcomes,” said Dr. Gamelin.

The value of personalized 5-FU dose management was also reinforced in two studies reported earlier this year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium. Results from these Phase II studies of metastatic colorectal cancer patients treated with 5-FU (in combination regimens commonly used in the U.S., FOLFOX and FOLFIRI) demonstrated improved response rates and reduced toxicities with blood level dose management.(1)

New, Multicenter Study Seeks to Use Faster, Less Expensive Blood Test

To date, analysis of 5-FU patient blood concentrations could only be performed by complex, labor-intensive methods, such as liquid chromatography-mass spectroscopy (LC-MS). Saladax Biomedical, Inc., a Bethlehem, Pa.-based biotech company, is sponsoring a soon-to-enroll study to support the case for blood-based 5-FU dose management with the FOLFOX regimen. The study will employ a new immunoassay based on a patented technology from Saladax. The assay, called Personalized Chemotherapy Management (PCM), provides LC-MS-like performance but is easier to use and less expensive.

The multicenter, randomized Phase III study will enroll more than 200 patients with metastatic colorectal cancer to determine the efficacy of 5-FU dose management utilizing the PCM test. Edward Chu, M.D., chief of Medical Oncology and deputy director of the Yale Cancer Center in New Haven, Conn., will be the lead investigator of the study, which will involve several other cancer centers in the U.S., as well as the Paul Papin Cancer Center in France.

“Therapeutic dose management is common for many important drugs in other areas of medicine. Based upon recent evidence that we can lower toxicity and improve efficacy with personalized 5-FU dose management, it makes sense to use this same approach in cancer treatment,” said Dr. Chu. “We hope that this study will provide oncologists with important evidence and guidance on the role of drug monitoring in their routine practice,” he added.

About Colorectal Cancer

Colorectal cancer is a worldwide public health problem, with more than 940,000 new cases diagnosed each year, resulting in approximately 500,000 deaths.(2) In the U.S., it is the third leading cause of cancer mortality, and in 2008, nearly 50,000 deaths will be attributed to this disease.(3) Its incidence rate is strongly correlated with age. Data from industrialized countries demonstrate that the incidence of colorectal cancer rises three-fold between the ages of 60 and 80 years.(4)

About Saladax

Saladax Biomedical is pioneering the development of novel, fast, and inexpensive immunoassays that will enable routine blood-level monitoring of anti-cancer drugs to become the standard-of-care in treating cancer patients. With Personalized Chemotherapy Management (PCM), oncologists will be able to adjust the administered dose based on each patient’s individual drug level, leading to reduced toxicity, improved outcome and lower cancer care costs. Saladax is headquartered at the business incubator of the Ben Franklin Technology Partners (BFTP) of Northeastern Pennsylvania on the campus of Lehigh University in Bethlehem. The 5-FU PCM test will be available to U.S. clinicians later this year through a major reference laboratory.

References

(1) Proceedings from the American Society of Clinical Oncology - GI, January 2008; Orlando, FL Abstract #429 & Abstract #431

(2) World Health Organization, “World Cancer Report.” April 3, 2003, http://www.who.int/mediacentre/news/releases/2003/pr27/en/(April 22, 2008).

(3) American Cancer Society, “What are the Key Statistics for Colorectal Cancer?,” March 5, 2008, http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statistics_for_colon_and_rectum_cancer.asp (April 22, 2008).

(4) Gamelin, E, Delva, R, Jacob, J, et al: “Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: Results of a multicenter randomized trial of patients with metastatic colorectal cancer.” J. Clin Oncol 13:2099- 2105, 2008.

(5) Saladax Biomedical
http://www.saladax.com