Opko Health Inc (OPK)

[tomsylver]

CTAP101 (Rayaldee)
Categories : OPKO Health, Prolor Biotech

Rayaldee™ Capsules (CTAP101 Capsules): ( http://www.cytochroma.com/pipeline/product_candidates.html )

Rayaldee Capsules is a modified-release formulation of 25-hydroxyvitamin D3 (calcifediol) being developed as a new monotherapy to treat secondary hyperparathyroidism (SHPT) associated with vitamin D insufficiency in patients with Stage 3 through 4 chronic kidney disease (CKD). This orally administered product is designed to gradually restore serum total 25-hydroxyvitamin D concentrations to (or above) the currently accepted minimum adequate level of 30 ng/mL. It has potential application as an adjunctive therapy to vitamin D hormone replacement therapy for SHPT in patients with Stage 5 CKD. It also has potential application as adjunctive therapy to bisphosphonate, selective estrogen receptor modulator (SERM) and anti-RANK ligand (RANKL) treatment for metabolic bone diseases, including osteoporosis and metastatic bone cancer.

A randomized, double-blinded, dose-ranging placebo-controlled Phase 2b trial was completed in Q4’11. Data from this trial demonstrated that the product reliably corrected vitamin D insufficiency and effectively reduced elevated plasma intact parathyroid hormone (PTH) in the target patient population without adversely affecting serum calcium and phosphorus. These data were presented to the U.S. Food and Drug Administration (FDA) in Q1’12 during an end-of-Phase 2 meeting. At the FDA’s recommendation, a Special Protocol Assessment (SPA) was completed in Q3’12 for the planned Phase 3 trials, and the actual trials started shortly thereafter. Final data from these trials are anticipated in Q3’14. A 505(b)(2) new drug application (NDA) filing in the U.S. is targeted for H1’15. Rayaldee Capsules are protected until at least 2028 in the U.S. by method of use patents. Additional pending method of use and formulation patent applications are expected to protect the product through 2028 and beyond in all major global markets.

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Renal & Urology News ( http://issuu.com/haymarket/docs/renal-and-urology-news-june-2012 )  ?LINK ( http://issuu.com/haymarket/docs/renal-and-urology-news-june-2012 )
June 2012 Vol 11, Issue No#6
Amit Sharma, MD Chief Medical Officer at Pacific Renal Research Institute in meridian, Idaho.

Amit Sharma, M.D., is an accomplished board certified nephrologist, internist, and hypertension specialist who has a broad-based background in chronic kidney disease and dialysis. Recently, Dr. Sharma was Medical Director, Medical Affairs, at Reata Pharmaceuticals. From 2005-2012, Dr. Sharma served as a Medical Director and Senior Advisor for Liberty Dialysis, LLC, a medium-size dialysis organization with over 300 dialysis clinics. Liberty was sold in 2011 to Fresenius Medical Care AG for $1.7 billion. From 2001 to 2005, Dr. Sharma served as the Director of the Dialysis Unit and of the Chronic Kidney Disease Clinic for the Naval Medical Center, San Diego.

Dr. Sharma received his medical degree from Louisiana State University Medical Center-New Orleans. He completed his fellowship in Nephrology and Hypertension from University of California in San Diego in 2001. Dr. Sharma also has extensive experience conducting primary research and as a principal investigator for numerous clinical trials in the field of nephrology and hypertension. He has published in many respected peer reviewed journals and he is a well known presenter for national and international meetings.

In reference to CTAP101 (Rayaldee), Dr. Sharma said. "A new therapy that has the ability to significantly raise 25D levels and lower iPTH in his patient population would be of significant benefit for our practice." ( http://issuu.com/haymarket/docs/renal-and-urology-news-june-2012 )

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January 14, 2013 
BioTrends Research Group: ( http://bio-trends.com/News-and-Events/Press-Releases/TreatmentTrends-US-Nephrology-011413 )
Physician familiarity with Cytochroma's CTAP101, capsules for the treatment of vitamin D insufficiency, is low at this point in time but respondents estimate that nearly 35 percent of dialysis patients are likely candidates for the product. Also, 23 percent believe CTAP101 will likely be used in combination with active vitamin D.

July 8, 2013
BioTrend Research Group: ( http://bio-trends.com/News-and-Events/Press-Releases/TreatmentTrends-Nephrology-070813 )
Nephrology (U.S.) Q2 2013 report finds that more than 45 percent of surveyed nephrologists are highly interested in OPKO Health's CTAP101

July 10, 2014
BioTrends Research Group: ( http://www.bio-trends.com/News-and-Events/Press-Releases/Nephrologists7-10-14 )
OPKO Health’s Rayaldee: While familiarity is low, over 40 percent of nephrologists report high interest in this oral Vitamin D therapy used to treat SHPT being tested in CKD stage 3 and stage 4 patients, after review of a product profile.

February 21, 2014
Applied Investment Management Marquette University: ( http://business.marquette.edu/Content/Uploads/AIM/equity-writeups/2-21-14.pdf )  There are approximately 8.5 million patients in these stages of kidney disease, of which 7.4 million have vitamin deficiency. Over 90% of Nephrologists surveyed expressed a moderate to high need for a therapy to raise 25D levels in kidney failure patients. Estimates project Rayaldy can obtain a 30-50% market share, which represents $12 billion annually.

*BioTrends Research Group ( http://www.bio-trends.com/ ) , a Decision Resources Group company, is the leader in providing specialized, syndicated market research to clinically complex, small to mid-size pharmaceutical companies.
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OPKO Health Inc. And Rayaldy ( http://seekingalpha.com/article/1739772-opko-health-inc-and-rayaldy )
Oct. 10, 2013
John Cannell, MD ( http://opkodd.wordpress.com/2014/04/03/john-j-cannell-md-biography/ )

Three weeks ago, I invested all my available funds in OPKO Health Inc. (NYSE:OPK). I did that when I learned about its new vitamin D drug, Rayaldy.

I am not a stock analyst, adviser, or investment expert. Instead, I am a physician and an expert on vitamin D. Ten years ago, I established the Vitamin D Council, a non-profit dedicated to educating the public and health professionals about vitamin D. I have written more than 15 peer-reviewed scientific articles on vitamin D. I have been reading, writing, and lecturing about vitamin D for the last 12 years.

Vitamin D (cholecalciferol) is not a vitamin in that it is not contained in any appreciable quantity in the food we eat, including milk. Instead, it is a prohormone made in the skin upon exposure to sunlight -- something that most of us have come to avoid during the last 30 years. Vitamin D is the only known building block for a potent seco-steroid hormone known as calcitriol. Vitamin D is metabolized to calcitriol in two steps via a more active prohormone intermediate known as calcifediol, the circulating form of vitamin D. Like corticosteroids and other steroid hormones, calcitriol directly regulates hundreds if not thousands of human genes. In calcitriol's case, those genes are involved with the repair and maintenance of the human body. It is crucial to realize that steroid hormones have as many mechanisms of action in various diseases as genes they regulate.

Science has discovered much about vitamin D in the last ten years, almost all of it promising. If they know anything about vitamin D, most people think of it as something that may protect against various diseases. Indeed, the evidence is so strong for prevention of disease, four large and very expensive phase 3 trials are currently underway around the world to see if vitamin D prevents common diseases like cancer and heart disease. The largest of these trials is the VITAL study at Harvard where scientists are conducting a randomized controlled trial of vitamin D in 20,000 Americans. Obviously, these large studies would never have been funded unless solid reasons exist indicating these vitamin D trials will be positive. For more on vitamin D, go to Harvard School of Public Health's website on vitamin D.

While everyone seems intent on studying vitamin D's preventative effects, few have noticed that scientists have published dozens of small randomized controlled trials in the last few years, documenting that vitamin D has treatment effects, not just preventative effects. These small "phase 2" trials show over-the-counter (OTC) vitamin D has a treatment effect in several diseases, especially autoimmune diseases like multiple sclerosis. In addition, "phase 2" trials exist, showing vitamin D has efficacy in treating diseases as diverse as major depression, falls in the elderly, atopic dermatitis, congestive heart failure in infants, hypertension in African Americans, and tooth loss in the elderly. Treatment effects are not cures; rather, they are simply clinical or laboratory improvements. Besides the randomized controlled trials, hundreds, if not thousands, of epidemiological studies now exist, suggesting that vitamin D will have treatment effects in an even wider variety of human disease.

OPKO Health's new drug, Rayaldy, is the first and only modified-release formulation of calcifediol, protected by newly issued patents (see, for example, US Patent No. 8,361,488). It is currently in phase 3 trials for the treatment of secondary hyperparathyroidism in vitamin D insufficient patients with chronic kidney disease (CKD). Its phase 2 trials for this indication were very positive. Rayaldy is much more potent than OTC vitamin D and it corrects vitamin D insufficiency more effectively and reliably than does OTC vitamin D. Also, Rayaldy is less prone to degradation in the body than is OTC vitamin D because of gradual delivery of calcifediol from its modified-release formulation.

If the FDA will eventually approve Rayaldy; OPKO Health will certainly study more indications for its new drug than just secondary hyperparathyroidism in CKD. According to the current medical literature, phase 3 trials targeting new indications could confirm treatment effects in a wide variety of human diseases.

Of course, risks exist. I may be wrong about vitamin D; similar enthusiasm for other vitamins in the past did not pan out. Larger randomized controlled trials may fail to find treatment effects with vitamin D. Also, Rayaldy's current phase 3 trials may turn out to be negative. Eventually, other companies may enter the market with different modified-release formulations of vitamin D. OPKO Health may not aggressively seek other indications, settling only for the multibillion-dollar CKD market.

Rayaldy is currently the only product of its type in development by any drug company, as far as I am aware. Currently available prescription vitamin D hormone therapies have significant limitations or side effects, something not seen with Rayaldy. Physicians will soon have a choice: tell their patients to go to the corner drug store to buy OTC vitamin D or prescribe the more potent and reliable and less degradable Rayaldy.

Again, it is important to realize that steroid hormones like calcitriol and corticosteroids have as many mechanisms of action as genes they regulate. The number of genes directly regulated by corticosteroids is estimated to be around 100, almost all having to do with inflammation. However, calcitriol regulates 1,000 human genes. Calcitriol's genetic mechanism of action not only includes anti-inflammatory actions, but extends to mechanisms involving DNA repair, anti-autoimmune actions, mechanisms involving brain development and functioning, profound effects on the immune system, cardiovascular functioning, lung function, liver function, and pancreatic function, to name a few.

In my opinion, sales of Rayaldy-like drugs will eventually easily outstrip the sales of corticosteroids.

*About:

John Jacob Cannell was born in Washington, DC on June 21, 1948. Understanding why he founded the Council begins with an understanding on his interest and background in activism.

During his college years he had a penchant for social activism and was deeply involved in working against the Vietnam War. While at the University of Maryland he helped organize the “March on Washington” and also demonstrated against the war at the 1968 Chicago Democratic Convention. He finished up his undergraduate work at the University of Maryland where he graduated in Zoology and was a member of Phi Beta Kappa.

Cannell then went on to medical school at the University of North Carolina. After a year of a surgery internship at the University of Utah and four years of practicing itinerant emergency medicine, he began as a general practitioner in the coalfields of Appalachia.

The Black Lung debate

In 1983 Dr. Cannell started the Cannell Clinic, Inc. in Flat Top, West Virginia. It wasn’t long before he noticed that all of his coal-mining patients smoked cigarettes, prompting him to start an anti-smoking campaign. His efforts included asking businesses not to sell cigarettes, running television ads and refusing to accept patients into his clinic unless they stopped smoking. The New York Times took notice and ran a story on his anti-smoking activities in February of 1988.

Cannell had to give up on his efforts against smoking. In West Virginia, coalminers would often smoke in order to get Black Lung and enroll in the Black Lung disability fund. Coal miners who have never smoked often do not have the severe pulmonary function deterioration found in smoking miners, and thus no Black Lung.

Cannell lobbied the members of the West Virginia Medical Society, asking for a resolution to stop using pulmonary function testing to award Black Lung benefits and instead endorse years of service as the basis for receiving the benefit, to put an end to smoking encouragement. Unfortunately, this was to no avail.

Yet despite all this, nothing changed. The schools continued to give the tests, administrators proudly reported the scores, and newspapers dutifully printed the “above average and improving” stories. It made everyone look great: politicians, school administrators, teachers and parents. It was a perfect con where everyone benefited except the kids being told they are doing okay when they were likely destined to graduate functionally illiterate.

After realizing that publicity would not end the widespread cheating on standardized tests, Cannell went back to begin a psychiatry residency at the University of New Mexico. He was immediately confronted with the McMartin/Bucky day care case in Manhattan Beach, California. After watching TV interviews of the defendants, Cannell immediately suspected that the defendants were entirely innocent and what was happening in Manhattan Beach was the most fatal of all psychiatric conditions, mass hysteria.

Cannell realized that recovered memory therapy (RMT) was at the heart of the hysteria, a form of psychotherapy in which patients recovered memories of abuse that they had no previous memory of. Such therapy resulted in false memory syndrome (FMS) of events that never occurred as well as an epidemic of multiple personality disorder (MPD), a rare disorder historically conceived of as being a hysterical disorder. Unfortunately, many MPD patients believed the psychiatrist conducting the RMT and went home to falsely accuse their parents and others of horrendous acts that never occurred. Cannell teamed up with two Harvard professors to write a peer reviewed paper on RMT.

Many of the RMT and MPD patients eventually retracted their allegations but not before they had hurt others or destroyed their families. Cannell realized these “retractors” had standing to file suit against their recovered memory therapists. Cannell then sponsored two conferences, one in Missoula, Montana, and one in Seattle, Washington, on RMT and FMS. Cannell invited retractors and tort lawyers to hear memory experts from Harvard, John Hopkins, and University of Washington speak about the science of memory and the reality of FMS.

At the conferences, many believers became retractors and the retractors found attorneys while the attorneys found plaintiffs. The attorneys also heard potential expert witnesses (Professors James Hudson and Harrison Pope from Harvard, Professor Paul McHugh, Chairman of the Department of Psychiatry at John Hopkins, and Professor Elizabeth Loftus, the renowned memory expert) speak. Hundreds of torts (lawsuits) emerged as a consequence of the conferences, exactly Cannell’s goal.

In the late 1990s, Cannell testified in dozens of FMS and MPD cases around the country against fellow psychiatrists who had practiced RMT. The suits were wildly successful resulting in multi-million dollar verdicts for the retractors and against the psychiatrists. Soon, insurance companies stopped covering RMT, which, together with MPD, disappeared, almost overnight. Unlike his anti-smoking and public school reform efforts, Cannell had finally been part of a successful social movement, the end of RMT and MPD.

The formation of the Vitamin D Council

Discouraged over having wasted so much time, effort, and money trying to improve public education and needing a change in his life, Cannell left general practice and went back to school to study psychiatry. He moved to Atascadero, California, in the late 1990s and began working as a psychiatrist at Atascadero State Hospital, the largest hospital in America for the criminally insane. There, he became deeply interested in food and nutrition and their roles in American health.

As Cannell began to study vitamin D, he quickly realized that public recommendation for vitamin D were probably way off the mark. Cannell concluded that if one totally avoids the sun and then strictly follows public recommendations, one will eventually develop vitamin D deficiency.

In 2003, he recruited professional colleagues, friends, and family to form the 501(c)(3) nonprofit the Vitamin D Council and take action to ensure people were getting enough vitamin D.

Lake Woebegone and fraudulent testing

It wasn’t much longer until Cannell found a new cause. In the late ’80s, the Beckley Register/Heraldran a story stating that all 55 West Virginia counties were above the national average on commercial elementary standardized achievement. Cannell read the stories and decided to do some investigating.

Upon researching “normed referenced” commercial elementary achievement tests, Cannell discovered that the commercial publishers are free to choose their own “norm group” (a group of students said to represent the average which are given the test without any test preparation). The publishers sold the test booklets, the norms, and the answer keys to school officials to reuse each year.

Given this, all 50 States were claiming to be above the national average, because compared to fake test norms, they were. And the U.S. Department of Education confirmed that they did not regulate or oversee commercial achievement testing in the United States. They did not consider it their business as it was the for-profit business of commercial test publishers.

This led Cannell to form the nonprofit, Friends for Education, in 1986, in attempt to reform the education system and bring attention to State’s fraudulent claims of being above the norm. Friends for Education filed consumer fraud complaints with the Attorney Generals of all fifty States. Secretary of Education William Bennett held a special meeting about the issue, Congress held hearings on “Lake Woebegone” testing, and 60 Minutes featured a segment on Cannell’s work exposing the fraudulent testing. The story also got high-profile coverage in the New York Times, the Wall Street Journal, plus hundreds of other newspapers. It even received segments on the McNeill/Lehrer Show and Sunday Today.