The NAS has a very strong position toward independence of business and politics and tries to maintain a position of science. NAS Conflicts of Interest Policy: “Finally, it is essential that the work of committees that are used by the institution in the development of reports not be compromised by issues of bias and lack of objectivity.”

The Institute of Medicine is a division of the National Academy and one of its responsibilities is to determine the daily required intakes of nutrients through its Food and Nutrition Boards.  I thought that it would be interesting to see if there was opportunity for conflict on the recent FNB for vitamin D and calcium.

Before we can decide if there exists a conflict of interest, we must first establish opportunity.  It is well established that the larger the amount of money involved, the larger the opportunity for conflict.  (Aside, I just love how today we mince words and use words like conflict instead of corruption.)  I asked the question about how large the vitamin D industry could be.  I decided to use Dr. William Grant’s, an epidemiologist with SUNARC, studies.  He has stated that moving the serum level of vitamin D, 25(OH)D, from 20 ng/ml to 40 ng/ml would reduce all cause mortality by fifteen to twenty percent and reduce the medical economic burden by ten percent.  The five studies done to arrive at these numbers were for Canada, US, Netherlands, Nordic countries, and Western Europe.  If we estimate the size of the Canadian and US medical economy at 2.5 trillion dollars per year then a reduction in economic burden ten percent would be 250 billion dollars.  The recent FNB decided to keep the standard target for 25(OH)D at 20 ng/ml as that is high enough for bone health and most of the population is close to that level.

Before we proceed, you should understand the meaning of a pharmaceutical analog.  An analog is something that represents or analogous to another thing.  In chemistry, an analog only needs to have a similar structure, but not necessarily the same chemical and biological properties.  This allows the maker of an analog for a natural substance to develop patents for commercial purposes.

Consultant – Hector F. DeLuca, University of Wisconsin Madison

This from the Wisconsin Alumni Research Foundation http://www.warf.org , an entity designed to develop patents and income from licensing arrangements for the patents.  The holder of the patent gets twenty percent of the royalties from the licensing according to information from WARF’s web site.

Business opportunity on osteoporosis and other bone disease from WARF http://www.warf.org/industry/index.jsp?cid=55&scid=76

Business Opportunity

• Osteoporosis is a growing market and under-diagnosed disease in the United States. In 2009 it is estimated that 11 million people and 18% of the US population over the age of 50 have osteoporosis. This number is expected to exceed 14 million by 2021.
• The U.S. osteoporosis market generated revenues of $4.7 billion in 2008 and is expected to generate $6.5 billion by 2021.
• Almost 90% of the treatments currently marketed for osteoporosis do not provide anabolic bone formation activity as their mechanism of action.
• A clear need exists for new products that can improve current approaches to reducing fracture risks by forming new bone as well as preserve existing bone.
• Extensive intellectual property rights may already be established in major market areas.

At the present time, a significant late stage commercialization opportunity is available through our Licensee, Deltanoid Pharmaceuticals. For further information, please contact our office.

Additional Information
For more information about the inventor, see Hector DeLuca

Prostate Cancer: UW–Madison researchers are designing non-calcemic analogs of calcitriol with anti-cancer effects on prostate cancer cells.

http://www.warf.org/industry/index.jsp?cid=55&scid=77

Business Opportunity

• Prostate cancer is a growing market worldwide.
• A need remains unmet for non-invasive treatments and fewer treatment-related side effects.
• A major gap in the market exists, offering high commercial potential for second line treatment of hormone refractory prostate cancer (HRPC).

Applications

• Treatment for all forms of prostate cancer.
• Suitable as an oral or intravenous formulation.

Key Benefits

• A proven biologically active compound that stops growth of prostate cancer cells.
• Provides a safer, less calcemic compound than the natural hormone calcitriol.
• Offers a fresh therapeutic approach for gaining access to the cancer therapy market.
• Provides a drug development opportunity in a growing market space.
• Innovative licensing and development terms available.

Stage of Development
The analogs offered in this portfolio have been subjected to in vitro/in vivo models for early-stage pre-clinical evaluation.

Please contact our office for updates as study data sets may be evolving with compounds under development.

Additional Information
For more information about the inventor, see Hector DeLuca

Psoriasis: http://www.warf.org/industry/index.jsp?cid=55&scid=78

WARF maintains a robust and growing portfolio of low and non-calcemic analogs of calcitriol. Intellectual property rights and special development incentives for commercialization in the psoriasis space are currently available.

Business Opportunity

• Through 2006, the prevalence of psoriasis was estimated to be 17 million people worldwide.
• Datamonitor reports $1.95 billion in sales of psoriasis treatments in 2005.
• By 2015 the market for psoriasis treatments will exceed $2.3 billion in the U.S., $832 million in the E.U. and $354 million in Japan.
• An increasing demand exists for safer therapeutics that control symptoms with greater efficacy, longer duration and improved quality of life.
• Providers view vitamin D analog treatments as first line options versus steroids due to safety concerns and also over biologic treatments as payers carefully scrutinize risk-benefit and cost-benefit ratios.
• Next generation vitamin D treatments are needed to replace older products with narrow therapeutic indexes.

Applications

• Mild psoriasis
• Severe psoriasis

Key Benefits

• A proven biologically active compound that slows the growth of skin cells with minimal potential for raising calcium levels.
• May enable less frequent dosing and increase in size of treatment areas.
• Early pre-clinical screening studies completed; later stage pre-clinical and clinical GLP evaluations may be available.
• Offers a fresh therapeutic approach for gaining access to the growing psoriasis and skin therapy market.
• Innovative licensing and/or development terms available.

Stage of Development
The analogs offered in this portfolio have been subjected to in vitro/in vivo models for evaluations of receptor binding, cell proliferation, cellular differentiation, calcium mobilization and blood calcium levels. In some cases, Good Laboratory Practice (GLP)-rated pre-clinical and clinical data may be available for evaluation.

Please contact our office for updates as study data sets may be evolving with compounds under development.

Additional Information
For more information about the inventor, see Hector DeLuca

Chronic Kidney Disease: http://www.warf.org/industry/index.jsp?cid=55&scid=79

Business Opportunity

• The market for vitamin D analogs used to treat SHPT and renal osteodystrophy in the U.S. was estimated to be worth more than $800 million at the end of 2008.
• The U.S. Renal Data Service (USRDS) estimated approximately 330,000 people received dialysis treatment for stage 5 CKD in 2006 and that the U.S. CKD population is expected to increase 60% by 2020.
• In 1997, treatment of diabetic patients with stage 5 CKD in the U.S. cost more than $15.6 billion.
• Improving treatment outcomes relating to bone and mineral disorders is a central theme in CKD patient management strategies.

Applications

• Oral and intravenous treatments for management of SHPT and renal osteodystrophy in CKD patients.
• Prevention or treatment of diabetic nephropathy.
• Maintenance of kidney function in patients with early stage CKD.

Key Benefits

• Proven biologically active compounds selected to target and suppress PTH levels.
• Provides safer, less calcemic and less phosphatemic compounds than the natural hormone calcitriol or currently marketed treatments.
• Offers a fresh therapeutic approach for gaining access to the kidney disease market.
• Provides a drug development opportunity in a growing market space.
• Strong intellectual property rights and development incentives are available.

Stage of Development
Many of the analogs offered in this portfolio have been subjected to in vitro/in vivo models for evaluations of receptor binding, cell proliferation, cellular differentiation, bone and intestinal calcium mobilization. In some cases, Good Laboratory Practice (GLP)-rated pre-clinical and clinical data may also be available for evaluation.

Please contact our office for updates as study data sets may be evolving with compounds under development.

Additional Information
For more information about the inventor, see Hector DeLuca

Type 1 Diabetes: http://www.warf.org/industry/index.jsp?cid=55&scid=80

WARF maintains a robust and growing portfolio of low and non-calcemic analogs of calcitriol. Intellectual property rights and special development incentives for commercialization in the type 1 diabetes space are currently available.

Business Opportunity

• Diabetes affects 246 million people worldwide and nearly 8% of the U.S. population. By 2025 experts predict 380 million people will be afflicted with diabetes.
• In 2007, the five countries with the largest numbers of people with diabetes were India (40.9 million), China (39.8 million), United States (19.2 million), Russia (9.6 million) and Germany (7.4 million).
• Global diabetes treatment market was valued at over $21 billion in 2006.
• The Juvenile Diabetes Research Foundation estimates there are over 3 million people in the US with T1D and nearly 15,000 new cases of T1D diagnosed yearly.
• Multiple source funding is available for diabetes translational research.

Applications

• Prevention of type 1 diabetes in humans and other animals.

Key Benefits

• A proven biologically active compound with beneficial effects on beta cell and immune function.
• Provides a safer, less calcemic compound than the natural hormone calcitriol.
• Offers a fresh therapeutic approach for gaining access to the diabetes market.
• Provides a drug development opportunity in a growing market space.
• Innovative licensing and/or development terms available.

Stage of Development
The analogs offered in this portfolio have been subjected to in vitro/in vivo models for early-stage pre-clinical evaluation.

Please contact our office for updates as study data sets may be evolving with compounds under development.

Additional Information
For more information about the inventor, see Hector DeLuca

Multiple Sclerosis: http://www.warf.org/industry/index.jsp?cid=55&scid=81

At UW–Madison, promising research is underway with several noncalcemic vitamin D analogs that show efficacy in the EAE mouse model. These analogs may provide the solution to the dose limitations of calcitriol by offering a wider dose range and lower potential for causing hypercalcemia and its complications.

Business Opportunity

• Cure for MS is a large and unmet medical need.
• More than 350,000 individuals in the U.S. are affected.
• 200 new cases are diagnosed each week.
• Annual cost of MS in the U.S. is in the billions of dollars.

Applications

• Prevention and treatment for MS

Key Benefits

• A proven biologically active compound that may reduce the risk of developing MS or slow the progression of the disease.
• Provides a safer, less calcemic compound than the natural hormone calcitriol.
• Offers a fresh therapeutic approach for gaining access to the MS therapy market.
• Provides a drug development opportunity in a growing market space.
• Innovative licensing and development terms available.

Committee Member: Glenville Jones, Head, Department of Biochemistry and Professor of Biochemistry and Medicine, Queens University, Ontario

April 23, 2007 from the Queen’s Gazette Forum – by Glenville Jones “Steenbock’s Legacy: More than Vitamin D Fortified Milk” http://www.parteqinnovations.com/pdf-doc/fandr-Gaz0407.pdf about what Mr. Jones learned from the University of Wisconsin Madison and how analogs have helped millions.

From Cytochroma, Inc. web site: “Promoting Health through Vitamin D Therapies”

Mr. Jones is co-founder Cytochroma, Inc. and is on their advisory board: http://www.cytochroma.com/about_us/scientific_ad_board/jones.html

Dr. Jones is Craine Professor and Head, Department of Biochemistry at Queen’s University. Dr. Jones is an internationally respected researcher in the field of nutrition, metabolism and vitamin D. He was a founding member of the advisory board of the Canadian Institute of Nutrition, Metabolism & Diabetes, and has served six terms on the scientific program committee of the International Workshop on vitamin D. In 2004 Dr. Jones received a Career Achievement Award for his scientific contributions to the vitamin D field at the Thirteenth International Workshop on vitamin D.  Dr. Jones is a graduate of Liverpool University (BSc, PhD) and completed postdoctoral work at University of Calgary and University of Wisconsin, Madison. Prior to his appointment to Queen’s in 1984 he was a faculty member at the Hospital for Sick Children and University of Toronto. Dr. Jones is credited with the discovery of 1,25(OH)₂D₂ and is a named inventor on numerous patents and is author of more than 200 papers and presentations.  Dr. Jones is a co-founder of Cytochroma.

Statement by Glennville Jones after Cytochroma reached a licensing agreement with John Hopkins University for a vitamin D enzyme inhibitor from The Free Library http://www.thefreelibrary.com/Cytochroma+Inc.+licenses+novel+chemical+compounds+from+Johns+Hopkins…-a067579561 :  “Vitamin D plays a vital role in maintaining calcium levels in the body and in the regulation of cell proliferation and cell differentiation,” stated Dr. Glenville Jones, Co-Chief Scientific Officer responsible for the vitamin D program at Cytochroma. “We have every confidence this approach will lead to new drug candidates to treat malignancies which overexpress CYP24, such as prostate, breast and lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell.”

Have you decided yet about conflict of interest?  I guess the over site committee at the NAS was comfortable with the choices.  Does keeping the target 25(OH)D at 20 ng/ml allow for more business opportunity?

For information on possible conflicts see: http://www.vitamindwiki.com/tiki-index.php?page_id=1198