The Case of Synthroid B: Marketing a Drug Coming Off Patent Kellogg School of Management

Gross and Pitt rivers found that L-T3 was 5 times as more potent than L-Thyroxine at inhibiting the release of TSH from the pituitary gland. They also found that when both were delivered orally rather than subcutaneously (by injection), L-T3 was approximately twice as effective as thyroxine. I discuss them in chronological order, from the earliest thyroid medication to the most recently invented. The thyroid is a small butterfly-shaped gland located at the base of the neck, just below the Adam’s apple. It’sresponsible for controlling the body’s metabolism, or the rate at which the body converts food into energy, and for making sure the brain, heart, liver, kidneys, and other organs are working properly. Once thyroid hormone was found to work by Dr Murray, many other forms of hormone replacement were subsequently developed, like insulin for diabetes and oestrogen hormone replacement for the menopause.

• In my opinion, it is largely due to the massive marketing campaigns of the pharmaceutical companies that hold patents on these drugs.
• When your thyroid hormone level decreases, it results in your body’s system slowing down, including your metabolism, which may lead to symptoms such as sensitivity to cold, weight gain, and fatigue.
• More researchers and clinicians are recognizing that the current L-T4 monotherapy results in potential loss of Free T3 and a certain percentage of patients are still symptomatic.
• Thyroxine (T4) was isolated from pig thyroids in the early 1900s, but it was not in a form that was very useful in therapy until 1949, when a synthetic Levothyroxine (L-Thyroxine) medication was commercially launched by Glaxo.
• As with any medication, we are responsible to adapt the dose to the patient’s metabolic state and overall health.

Thyroxine

The (B) case describes what Abbott actually did to maintain its share in the United States and outlines its strategy in India, a market synthroid hyperthyroidism without patent protection for pharmaceuticals. Effectiveness is the most important criterion in choosing a thyroid replacement product. Natural thyroid extracts have been in use for over a century and were approved by the FDA in 1939, a year after the passage of the Food, Drug, and Cosmetic Act.

Monotherapy with LT4 has been the mainstay of management of hypothyroidism from about 1970. Thyroid research is far from complete, however, and further research into several outstanding clinical issues will continue to shape LT4-based therapy in the future. Studies of several animal models indicate that maintaining normal serum T3 levels is a biological priority (5). Although the clinical significance of relatively low serum T3 in humans is not well-defined (1), evidence shows that elevating serum T3 through the administration of both l-thyroxine and l-triiodothyronine has benefited some patients (6, 7).

• Within a decade there was a major transition toward l-thyroxine monotherapy as first-line therapy (Appendix Table and Figure) (38).
• The first attempts at iodine supplementation, either using a tincture of iodine, or with iodised salt, followed during the following decade 4.
• Treatment with LT4 + T3 combinations superseded the use of thyroid extracts from the 1960s onwards.
• For instance, in many l-thyroxine-treated patients with a normal serum TSH, the BMR remained at about 10% less than that of normal controls even after 3 months of therapy (53).
• I discuss them in chronological order, from the earliest thyroid medication to the most recently invented.

The advent of thyroxine and modern times

These were not designed as superiority trials, their therapeutic goals were the normalization of serum PBI or BMR, and doses were dramatically higher than used today. For example, desiccated thyroid and intravenous l-thyroxine monotherapy normalized BMR, pulse, and body weight in myxedema (29), l-triiodothyronine monotherapy was likewise effective (30), and the potency of l-triiodothyronine exceeded that of l-thyroxine (31). The introduction of pharmaceutical preparations of synthetic thyroid hormones and establishment of monotherapy with LT4 as the standard of care for hypothyroidism opened up a prospect of delivery of stable, reproducible therapy tailored to the needs of the individual patient. To achieve this, it was necessary to measure circulating levels of thyroid hormones accurately and reproducibly. These assays made it possible to accurately determine the thyroid status of patients with all degrees of severity of thyroid dysfunction and facilitated a leap in our understanding of the physiology of the thyroid gland.

• Levels of T4 and T3 are low in the setting of hypothyroidism, and the pituitary responds by increasing the secretion of TSH in an attempt to correct this, leading to an abnormally high TSH level 25.
• Holistic, functional medicine doctors in Houston, Texas specializing in bioidentical hormones, hypothyroidism, adrenal fatigue, menopause, perimenopause, low testosterone, allergies and LDI treatment, candida, detoxification, nutritional deficiencies, longevity and aesthetics.
• These clinical experiments arose from early studies of people we would today describe as having severe congenital hypothyroidism.
• The (B) case describes what Abbott actually did to maintain its share in the United States and outlines its strategy in India, a market without patent protection for pharmaceuticals.
• The discovery in 1895 of a substance containing high concentrations of iodine within the thyroid gland (“thyroiodine”) was therefore of considerable interest in unifying concepts relating to hypothyroidism and iodine, and the role of the thyroid as an endocrine organ 17.
• The relationship between levels of T4 and TSH is not linear, however, as decreasing the level of T4 by half results in an increase in the TSH level of as much as 100-fold 32.

Delegates travelled from as far afield as Australia and the USA to participate in the two-day event at Newcastle’s Centre for Life, which took place May 12-13. Synthetic Liothyronine has been used either alone or in combination with Levothyroxine since Liothyronine was first discovered.

A conference hosted by Newcastle University and the British Thyroid Association focused on recent treatment advances in thyroid disease and hormone replacement strategies. Triiodothyronine (T3) was first discovered in 1952, and was synthesized as Liothyronine in the same year. It was found to be far more potent than Levothyroxine in reducing pituitary inflammation, thyroid inflammation, and blood levels of cholesterol, and in raising the depressed basal metabolic rate that characterized hypothyroidism. In a 2017 survey of over 12,000 patients by the American Thyroid Association, patients gave DTE the highest rating compared with L-T4 monotherapy and T3/T4 combination therapy. Research continues into the management of hypothyroidism, and Table 1 highlights several important issues that remain unresolved 28, 32, 41–47.

Because naturally occurring substances, including thyroid hormone, cannot be patented, these products have a lower profit margin, and the companies that make them do not have millions of dollars at their disposal for marketing. In future, we may hope to see improved methods of delivery for both synthetic and natural T3-based therapies. The short half-life of T3 is cited as an inconvenience to patients, yet the “trouble” of taking several doses per day is a ridiculous obstacle to place in the way of improved health.

In the 1960s, the use of oral combinations of LT4 and T3 became widely used in the management of hypothyroidism, due to an assumption that delivery of both thyroid hormones would mimic the natural function of the thyroid gland 25. In addition, as thyroid extracts were essentially the reference product for clinical trials at this time, studies comparing thyroid extracts and LT4+ combinations gave broadly similar clinical results. In addition, it was discovered in the 1970s that about 80% of T3 in peripheral tissues is derived from local conversion from T4 by local deiodinases, rather than from the thyroid 27.

Oct 18, 2023How Natural Health Care Energized Peggy’s Life

As well as being used to treat thyroid under-activity in adults, thyroxine also works for babies who are born without a thyroid gland, and can be a critical factor for successful pregnancy and fertility in younger women. Currently the use of L-T3 therapy is seeing a revival as part of synthetic “combination therapy” alongside L-T4. At a current cost of only six pence per day, thyroxine medication for thyroid under-activity revolutionised the treatment of this common condition and this treatment is still in the top 10 of all medications prescribed in the world. “Considering that the idea of a ‘hormone’ hadn’t even been invented at this time, Dr Murray made a remarkable medical advance; one that millions of people continue to benefit from. Mackenzie went into detail of his patient’s condition during a sequence of pre-treatment hospitalizations ‘In order that it may not be imagined that the effect of treatment could be attributed simply to residence in the hospital’.

Figure. Events influencing the evolution of treatment trends in hypothyroidism.

In 2004, however, the FDA declared several competitive products to be bioequivalent to Synthroid, which posed a significant challenge to its owner, Abbott Laboratories. Students are challenged to consider options to maintain the drug’s unit volume, revenue, and/or profit in these difficult circumstances. The (A) case provides background on the history of the drug, the pharmaceutical industry and its marketing practices, and hypothyroidism and its treatment, and it concludes in 2004 as Abbott’s marketers face the impending challenge of defending the Synthroid business against generic competition.