Selling Low T Is Big Pharma Taking Big Risks with Patient Safety?

Transcription

1 Selling Low T Is Big Pharma Taking Big Risks with Patient Safety? An Overview of the Testosterone Replacement Therapy Marketplace and Potential Risks to Consumers Prepared by the attorneys of the Charles E. Boyk Law Offices, LLC 405 Madison Ave. Suite 1200 Toledo, Ohio Phone: Fax:

2 INTRODUCTION Thank you for taking the time to order this free report. If you are reading this publication, chances are that you or someone you know has taken a prescription testosterone replacement product and suffered an adverse event while on the drug. The purpose of this report is to educate the public on prescription testosterone treatments and the growing body of scientific studies linking testosterone replacement therapy to an increased risk of serious adverse cardiac events, including heart attacks, blood clots, strokes, and death. The purpose of this report is not to provide legal or medical advice, but solely to provide information to the public about the potential emerging health risk. Our firm is investigating individual cases on behalf of men across the nation who have suffered clots, heart attacks, strokes, or other serious side effects while using a prescription low T product. If you or a loved one has suffered any of these adverse effects, it is imperative that you seek legal assistance immediately. If you would like more information or a free case evaluation, please contact one of our highly experienced product liability attorneys by calling toll-free or by ing us at info@charlesboyk-law.com. You may also Live Chat 24 hours a day, seven days a week by visiting We hope that you find this publication to be straightforward, easy to read, and informative. If you would like one of the attorneys at the Charles E. Boyk Law Offices, LLC provide a free, no-obligation, consultation and analysis 1

3 of your situation, we encourage you to call We are always here to answer any questions that you may have. WHY DID WE WRITE THIS REPORT? As advocates for those facing serious injuries or death due to someone else s negligence, the attorneys in our office became concerned after reviewing several recent studies that suggest a link between the use of testosterone replacement therapy and serious adverse cardiac events. Recently, the market has been flooded with advertising for testosterone products that suggest a reversal of the symptoms of aging can easily and safely be achieved through testosterone replacement. This desire to fight the natural effects of aging have made testosterone replacement therapy a blockbuster market with sales already exceeding $1 billion annually, and the market for these products is expected to grow for years to come. What has not been well advertised or warned of by drug companies, however, are the potential harmful side effects of testosterone replacement therapy. The revelations of increased risk of heart attack, blood clot, stroke, and death, among men using prescription testosterone replacement drugs prompted the U.S. Food and Drug Administration in January 2014 to announce an investigation into the safety of these drugs and their risks to consumers. The failure of pharmaceutical companies to properly warn of the dangers associated with their products and instead, marketing their products as safe and effective, has given rise to federal litigation against the companies on behalf of individuals who have suffered a cardiovascular 2

4 injury after taking prescription testosterone. In light of this ongoing litigation, it is critical for the public to be aware of their rights and to understand the issues surrounding the marketing and risk of testosterone replacement treatment. It is our hope that this report helps serve that purpose. 3

5 WHAT IS TESTOSTERONE? In males, the principal sex hormones produced by the body are androgens. There are several different types of androgens, but the primary one is testosterone. Testosterone (T) is responsible for normal growth and development of the male, including sex organs and for maintenance of secondary sex characteristics. The biologic effects of T include increased body musculature and bone density, growth and maturation of male sex organs, development of male facial and body hair, and vocal cord thickening. T also has effects on behavior, sex drive, and sexual function. WHAT IS HYPOGONADISM AND HOW IS IT DIAGNOSED? Male hypogonadism is a clinical condition in which the testes do not produce androgen (testosterone). In order to diagnose hypogonadsim, a male should be experiencing (1) symptoms associated with a deficiency, as well as (2) have a laboratory finding of serum testosterone below accepted levels. i Symptoms and Signs of Hypogonadism: Suggestive symptoms of low T include, but are not limited to: Low libido; Erectile dysfunction; Decreased muscle mass and/or strength; Increased body fat, Decreased bone density, Loss of energy/fatigue; Sleep problems; Depression ii 4

6 The problem with associating these symptoms with low T is that many of these symptoms occur in other conditions or are physiologically associated with the aging process itself. Accordingly, these symptoms should be corroborated with a laboratory diagnosis of low T. Laboratory Diagnosis: According to the Mayo Clinic, a normal reference range of total T levels in adult men over the age of 19 years is ng/dl. iii Male hypogonadism results from low secretion of T and is generally characterized as concentrations of total T below 240 ng/dl (< 240 ng/dl). However, laboratory testing of T levels can have reliability issues and can vary wildly based upon a subject s pre-test activities. T levels are subject to variation, which can lead to misclassification. Exercise, diet, illness, certain medications, and even the time of day can all have an influence on T levels. In fact, research has shown that T levels can vary considerably between morning and afternoon as much as an average of 50% iv,v So for example, if a man had his T levels checked in the morning, when they are generally the highest, and had levels of 450 ng/dl, which is well within the normal range, it is entirely possible that his T levels could experience a normal drop to below 225 ng/dl later in the afternoon, falsely indicating he has hypogonadmism. As such, T levels are a relatively crude guideline and should not be used alone in diagnosing and treating hypogonadmism. Rather, in addition to low T levels, men should have clinical symptoms mentioned above. 5

7 HOW IS HYPOGONADISM TREATED? If a man has been diagnosed with androgen deficiency, he may be a candidate for testosterone therapy (TT). It should be a therapeutic goal to raise his T levels to the low to mid range of the reference range ( ng/dl) vi. Pharmaceutical companies have developed and commercialized several types of TT for low T. Following is a list of some of the most prevalent types of TT products in the U.S.: Intramuscular Injection: Until recently, injection therapy was one of the most frequently used treatment methods. Injections, usually self-administered, are taken at periodic intervals of typically two weeks or more. Available products include: DEPO-Testosterone, which is manufactured by Pfizer; and Delatestryl, which is manufactured by Endo Pharmaceuticals. Transdermal/Topical: Transdermal testosterone delivery includes daily gel applications and patches. These products are far and away the most prescribed products. They include: Forestra, which is manufactured by Endo Pharmaceuticals. Forestra is a gel that is applied once daily to the thighs in the morning. AndroGel, is currently promoted by AbbVie, formerly part of Abbott Labs, and Actavis AndroGel is applied once daily in the mornings to the shoulders and upper arms. 6

8 Androderm, is manufactured by Actavis, formerly Watson Pharm. Androderm is applied a patch product that is applied daily to the back, abdomen, upper arms, or thighs. Axiron, is manufactured by Lilly. It is a topical solution that is applied once daily, generally in the morning, to the underarms. Testrim, is manufactured by Auxilium Pharmaceuticals. It is a gel that is applied once daily to the shoulders and upper arms. Buccal: Buccal formulations of testosterone involve placing a product with a bioadhesive onto the gums where it delivers an extended dose of testosterone through the gums and cheeks. Available products include: Striant. Striant is currently marketed by Auxilium in the U.S. It is applied to the upper gum twice daily, approximately 12 hours apart. Subdermal Implant: Subdermal testosterone implants are surgically implanted underneath the skin. They deliver prolonged, steady-doses of testosterone. Products include: Testopel. Testopel is manufactured by Auxilium. Is placed underneath the skin where it delivers 3-6 months of testosterone. 7

9 HYPOGONADISM VERSUS LOW T The drugs listed above are approved treatments for hypogonadism resulting from the insufficient production and secretion of testosterone. Hypogonadism in younger men can be caused by a testicular disorder or disorder of the endocrine system. It can also develop as a result of disease or alcohol/drug abuse. However, in older males, testosterone levels gradually decline typically about 1 percent a year after age 30. vii As such, it is important to determine in older men if a low testosterone level is simply due to the decline of normal aging or if it is due to a disease or disorder. In an effort to increase the awareness, sales, and revenue of their products, drug manufacturers have sought to broaden the application of testosterone replacement therapy to the general public by portraying it as a fountain of youth that will allow men to combat the side effects of aging. In an effort to increase the visibility of their product, manufacturers have engaged in a campaign to rebrand hypogonadism as Low T. This campaign expands the physical symptoms traditionally associated with hypogonadism to broaden the appeal of the drugs. For example, according to a test developed by the drug manufacturers themselves, if one feels tired after dinner or is unable to play sports as well as he used to, he may be suffering from Low T and should consult his doctor about being placed on testosterone replacement drugs. Drug manufacturers have been extraordinarily successful in this campaign to rebrand hypogonadism as Low T. This success has allowed them to create a multibillion dollar market for prescription testosterone therapy in the United States. The size of the market, and the revenue 8

10 derived from it by the manufacturers, is only expected to increase in years to come. WHAT RISKS OF LOW T THERAPY HAVE DRUG MANUFACTURERS DISCLOSED TO THE PUBLIC? Even where an individual has been diagnosed with androgen deficiency and is a candidate for TT, it is critical that the health condition of the individual and risks of the TT are thoroughly reviewed before a prescribing decision is made. Each product label contains important information regarding: contraindications (health conditions that serve as a reason for not prescribing the TT); warnings (possible serious side effects); precautions (how to use the drug, possible drug interactions with other drugs); and adverse reactions (all side effects observed in studies of the drug). Accordingly to drug makers, common risks/reactions associated with the above TT products include: Increased risk of prostate cancer/prostate enlargement; Increased risk of hepatitis Gynecomastia (enlargement of male breast tissue/breast pain) Sleep apnea. In May 2009, the FDA issued an order to the makers of testosterone gel products to place a black box warning - the FDA s sternest warning - on their products, warning of the risks of secondary exposure after receiving numerous reports of children who were incidentally exposed. The children suffered adverse reactions such as premature 9

11 development, advanced bone growth, and aggressive behavior. SERIOUS CARDIOVASCULAR RISKS ASSOCIATED WITH LOW T THERAPY Although not warned of in most TT products, there are known associations between testosterone and heart disease. Most recently, two recent publications of two separate studies: In a 2013 study published in the Journal of the American Medical Association, researchers observed two groups of men who all had low testosterone levels and some underlying cardiovascular disease. One group of approximately 7500 men, who had an average age of 63, received no testosterone treatment. The other group of approximately 1200 men, who had an average age of 60, received testosterone treatment. The study found there was a 30% increased risk of stroke, heart attack, and death in the group that had the testosterone therapy. viii In a January 2014 study, researchers examined approximately 55,000 men of all ages who took testosterone. The study found that men aged 65 and older who had pre-existing cardiovascular issues, had more than doubled their risk of a heart attack within the first 90 days of taking testosterone. Among men younger than 65, who also had pre-existing history of heart disease, the study found the risk of heart attack in the first 90 days following the first prescription, nearly tripled. ix 10

12 In 2010, researchers conducted a clinical study involving treating men, 65 years of age and older, who had underlying health issues, with T. The study was halted after 23 subjects who were given T have cardiovascular-related adverse events, including death. x The increased risk of a cardiovascular event to men on TT could be attributed to the fact that T can cause a significant increase in the production of red blood cells. These extra red blood cells make blood thicker than normal. This can slow the flow of blood through small blood vessels, which can cause blood clots (thrombosis) to form. xi In a 2011 study, researchers found that the risk of clotting can be further magnified where the individual has a family history of thombophilia. Specifically, the researchers identified a genetic mutation (Factor V Leiden) that exists in about 5% of Caucasians in North America. Carriers of the factor V Leiden mutation have as much as an eightfold risk of thrombosis. xii The study also found that a significant number of men on TT had increased levels of the sex hormone estradiol. Estradiol is present in males as a result of a metabolic breakdown of testosterone. xiii Estradiol not only can cause male breast enlargement, but also can result in increased levels of plasma fibrinogen (a blood coagulating protein). Elevated plasma fibrinogen has been associated with increased risk of deep venous thrombosis (DVT) and/or pulmonary embolism. xiv 11

13 THE FDA IS REVIEWING CARDIOVASCULAR RISKS ASSOCIATED WITH TESTOSTERONE THERAPY On January 31, 2014, the U.S. Food and Drug Administration has announced that is currently investigating the safety of TT after the two recent studies, discussed above, linked the treatment to increased risks of cardiovascular injury. xv While the FDA investigates, it has cautioned healthcare professionals to consider whether the benefits of testosterone exceed the potential risks of treatment before prescribing. The FDA is also urging physicians and patients to report any side effects involving prescription T to its MedWatch program. xvi DRUG MANUFACTURERS LIABILITY FOR FAILING TO DISCLOSE THE RISKS OF LOW T THERAPY TO CONSUMERS TT is currently a $2 billion dollar a year business and expected to become a $5 billion dollar a year industry by xvii This is due in large part to the aggressive mass marketing campaigns of pharmaceutical companies which have created consumer perception that low T is prevalent and that TT is a simple, safe, and effective means to reverse the effects of aging caused by low T. In fact, in 2012, drug makers spent over $100 million to promote low T awareness and their TT drugs. 12

14 U.S. Annual Sales 2012 Topical Market $233.4M $95M $30.6M $257M $1.2B AndroGel Axiron Testim Androderm* Forestra * Androderm s 2011 sales. However, many of the drug makers downplayed or outright ignored the serious health risks to men, particularly the risks of cardiovascular injuries, such as blood clots, deep vein thrombosis, pulmonary embolisms, heart attacks, or strokes. While the Mayo Clinic s reference range for diagnosing low testosterone is ng/dl, drug makers have utilized a physiologic range of anything less than 300 ng/dl, which results in a higher population of men to be categorized as hypogonadic. Suits are now being filed in federal courts across the country by individuals who have suffered these injuries. They are seeking to hold these drug makers accountable for releasing these T drugs without adequate warnings which were known and which could have prevented serious injuries or death. Specifically, it is alleged that drug makers failed to properly warn and/or misrepresented to the public and to the medical community that TT is safe and free from serious 13

15 side effects. These suits are being filed all over the country, however they are likely to be consolidated and transferred to a single federal court. WHERE TO TURN IF YOU HAVE BEEN INJURED Those on TT should seek immediate medical help if they suffer from heart palpations, chest pain, difficulty breathing, or undue fatigue. Individuals on TT should reassess whether the treatment is appropriate and safe for them. However, individuals should consult with their physician before stopping any treatment, as there may be adverse effects associated with stopping. Our firm is investigating individual cases on behalf of men across the nation who have suffered clots, heart attacks, strokes, or other serious side effects while using a prescription low T product. If you or a loved one has suffered any of these adverse effects, it is imperative that you seek legal assistance immediately. Our firm is handling testosterone therapy cases on a contingency basis, meaning that you will not pay anything unless we recover compensation on your behalf. If you would like more information or a free case evaluation, please contact one of our highly experienced product liability attorneys by calling toll-free or by ing us at info@charlesboyk-law.com. You may also Live Chat 24 hours a day, seven days a week by visiting 14

16 WE CAN HELP YOU Charles E. Boyk has been in private practice for over 30 years and heads the Charles E. Boyk Law Offices, LLC. During his career, he is handled thousands of tort cases ranging and he has conducted numerous seminars for other attorneys to help them understand the world of personalinjury law. Many of Chuck s serious injury cases have garnered the attention of the national media, and have been featured by the Associated Press, CBS, NBC, ABC, Fox, The Huffington Post, The San Francisco Chronicle and the Detroit Free Press. This media coverage has helped to spread the word about the injustices suffered by our clients, in hopes of preventing other similar situations from happening. He has also regularly earned for his clients front-page newspaper and breaking news TV coverage. During the past 30 years, Chuck has acted as counsel or co-counsel in numerous cases across the United States, including California, Florida, Indiana, South Carolina, Michigan and New York. Chuck Boyk is a lifelong resident of Ohio. He has received a 10.0 "Superb" rating from the Avvo lawyer ranking system, one of the leading websites that provides information about lawyers to consumers. Chuck s firm also received an AV Rating from Martindale Hubbell, which is the highest ranking a law firm can earn. Michael A. Bruno has also been practicing law for over 30 years. Mike, who was named an Ohio Super Lawyer by Thomson Reuters, has a unique background that benefits our clients. Mike has handled more than 100 jury trials, and is one of the few attorneys in the area that is Board Certified 15

17 by the National Board of Trial Advocacy. His extensive experience in helping those who have been injured due to the negligence of someone else has earned Mike a perfect 10 rating by Avvo and an AV rating by Martindale Hubbell, the highest rating an attorney can receive. Wesley D. Merillat is an experienced attorney who has handled complex litigation cases. Wes is the lead attorney responsible for class actions and Multi-District Litigation in both Federal and state courts, primarily in the areas of pediatric litigation and pharmaceutical and product liability. Although many of his cases have been successfully resolved without the need for a trial, Wes' experience also includes successful bench and jury trials, as well as mediation and arbitration. A true advocate for justice, Wes has been involved in litigation against some of the country's largest companies, including: Ford Motor Company; Johnson & Johnson; Bayer Corporation; AT&T; Sprint; Verizon; T-Mobile; Wal-Mart; Netflix; Merck & Co., Inc.; Baxter Pharmaceuticals and Small Smiles dental centers. Zachary J. Murry has assisted in the representation of individuals, corporate, and institutional clients in numerous litigation and arbitration proceedings. He has worked on behalf of victims of dangerous products and defective pharmaceutical drugs in both state and federal multi-district litigation proceedings including the Yasmin/Yaz products liability litigation, and the Depuy ASR Hip Implant products liability litigation. This Book Does Not Offer Legal Advice We are happy that you have taken the time to read this special report. You should note, however, that ordering 16

18 or reading our report does not constitute an attorney-client relationship. We also are not offering a legal opinion in these pages because every case is different. If you want our legal opinion, please contact us at or We will be happy to set up a free meeting with you. i American Society for Reproductive Medicine, 2008;90:S83 7, Androgen deficiency in the aging male. ii Geriatrics Sep; 62(9):15-8, Review Testosterone replacement in elderly men iv J Clin Endocrinol Metab. Mar 2009; 94(3): , The Effect of Diurnal Variation on Clinical Measurement of Serum Testosterone and Other Sex Hormone Levels in Men iii v vi J Clin Endocrinol Metab. 2007;92: , Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. vii viii JAMA. 2013;310(17): doi: /jama , Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels 17

19 ix PLOS ONE, DOI: /journal.pone , Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men x N Engl J Med Jul 8;363(2): doi: /NEJMoa xi N Engl J Med.,2010 Jul 8;363(2): doi: Adverse events associated with testosterone administration xii Lancet. 1994, 344: , Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation xiii Reproductive Biology and Endocrinology: doi: / , Aromatase expression and role of estrogens in male gonad : a review" xiv Thromb Haemost 1994;71: , Factor VII and fibrinogen levels as risk factors for venous thrombosis. a case-control study of plasma levels and DNA polymorphisms the Leiden Thrombophilia Study xv xvi The MedWatch online reporting form can be found here: xvii 18