What Do *You* Think? Smartwatch Measures Cortisone

Posted on February 17, 2022 by MaryO

Share your thoughts here.

The human body responds to stress, from the everyday to the extreme, by producing a hormone called cortisol.

To date, it has been impractical to measure cortisol as a way to potentially identify conditions such as depression and post-traumatic stress, in which levels of the hormone are elevated. Cortisol levels traditionally have been evaluated through blood samples by professional labs, and while those measurements can be useful for diagnosing certain diseases, they fail to capture changes in cortisol levels over time.

Now, a UCLA research team has developed a device that could be a major step forward: A smartwatch that assesses cortisol levels found in sweat—accurately, noninvasively and in real time. Described in a study published in Science Advances, the technology could offer wearers the ability to read and react to an essential biochemical indicator of stress.

“I anticipate that the ability to monitor variations in cortisol closely across time will be very instructive for people with psychiatric disorders,” said co-corresponding author Anne Andrews, a UCLA professor of psychiatry and biobehavioral sciences, member of the California NanoSystems Institute at UCLA and member of the Semel Institute for Neuroscience and Human Behavior. “They may be able to see something coming or monitor changes in their own personal patterns.”

Cortisol is well-suited for measurement through sweat, according to co-corresponding author Sam Emaminejad, an associate professor of electrical and computer engineering at the UCLA Samueli School of Engineering, and a member of CNSI.

“We determined that by tracking cortisol in sweat, we would be able to monitor such changes in a wearable format, as we have shown before for other small molecules such as metabolites and pharmaceuticals,” he said. “Because of its small molecular size, cortisol diffuses in sweat with concentration levels that closely reflect its circulating levels.”

The technology capitalizes on previous advances in wearable bioelectronics and biosensing transistors made by Emaminejad, Andrews and their research teams.

In the new smartwatch, a strip of specialized thin adhesive film collects tiny volumes of sweat, measurable in millionths of a liter. An attached sensor detects cortisol using engineered strands of DNA, called aptamers, which are designed so that a cortisol molecule will fit into each aptamer like a key fits a lock. When cortisol attaches, the aptamer changes shape in a way that alters electric fields at the surface of a transistor.

The invention—along with a 2021 study that demonstrated the ability to measure key chemicals in the brain using probes—is the culmination of a long scientific quest for Andrews. Over more than 20 years, she has spearheaded efforts to monitor molecules such as serotonin, a chemical messenger in the brain tied to mood regulation, in living things, despite transistors’ vulnerability to wet, salty biological environments.

Sweating the small stuff: Smartwatch developed at UCLA measures key stress hormone
The technology capitalizes on previous work by Sam Emaminejad, Anne Andrews and their UCLA research teams. Credit: Emaminejad Lab and Andrews Lab/UCLA

In 1999, she proposed using nucleic acids—rather than proteins, the standard mechanism—to recognize specific molecules.

“That strategy led us to crack a fundamental physics problem: how to make transistors work for electronic measurements in biological fluids,” said Andrews, who is also a professor of chemistry and biochemistry.

Meanwhile, Emaminejad has had a vision of ubiquitous personal health monitoring. His lab is pioneering wearable devices with biosensors that track the levels of certain molecules that are related to specific health measures.

“We’re entering the era of point-of-person monitoring, where instead of going to a doctor to get checked out, the doctor is basically always with us,” he said. “The data are collected, analyzed and provided right on the body, giving us real-time feedback to improve our health and well-being.”

Emaminejad’s lab had previously demonstrated that a disposable version of the specialized adhesive film enables smartwatches to analyze chemicals from sweat, as well as a technology that prompts small amounts of sweat even when the wearer is still. Earlier studies showed that sensors developed by Emaminejad’s group could be useful for diagnosing diseases such as cystic fibrosis and for personalizing drug dosages.

One challenge in using cortisol levels to diagnose depression and other disorders is that levels of the hormone can vary widely from person to person—so doctors can’t learn very much from any single measurement. But the authors foresee that tracking individual cortisol levels over time using the smartwatch may alert wearers, and their physicians, to changes that could be clinically significant for diagnosis or monitoring the effects of treatment.

Among the study’s other authors is Janet Tomiyama, a UCLA associate professor of psychology, who has collaborated with Emaminejad’s lab over the years to test his wearable devices in clinical settings.

“This work turned into an important paper by drawing together disparate parts of UCLA,” said Paul Weiss, a UCLA distinguished professor of chemistry and biochemistry and of materials science and engineering, a member of CNSI, and a co-author of the paper. “It comes from us being close in proximity, not having ego problems and being excited about working together. We can solve each other’s problems and take this technology in new directions.”

The paper’s co-first authors are UCLA postdoctoral scholar Bo Wang and Chuanzhen Zhao, a former UCLA graduate student. Other co-authors are Zhaoqing Wang, Xuanbing Cheng, Wenfei Liu, Wenzhuo Yu, Shuyu Lin, Yichao Zhao, Kevin Cheung and Haisong Lin, all of UCLA; and Milan Stojanović and Kyung-Ae Yang of Columbia University.

From https://techxplore.com/news/2022-02-small-newly-smartwatch-key-stress.html

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Synergistic Cortisol Suppression by Ketoconazole–Osilodrostat Combination Therapy

Posted on January 31, 2022 by MaryO

Abstract

Summary

Here, we describe a case of a patient presenting with adrenocorticotrophic hormone-independent Cushing’s syndrome in a context of primary bilateral macronodular adrenocortical hyperplasia. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. The patient was finally successfully treated with a well-tolerated synergitic combination of ketoconazole and osilodrostat. We believe this case provides timely and original insights to physicians, who should be aware that this strategy could be considered for any patients with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

Learning points

  • Ketoconazole–osilodrostat combination therapy appears to be a safe, efficient and well-tolerated strategy to supress cortisol levels in Cushing syndrome.
  • Ketoconazole and osilodrostat appear to act in a synergistic manner.
  • This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.
  • Considering the current cost of newly-released drugs, such a strategy could lower the financial costs for patients and/or society.

Background

Untreated or inadequately treated Cushing’s syndrome (CS) is a morbid condition leading to numerous complications. The latter ultimately results in an increased mortality that is mainly due to cardiovascular events and infections. The goal of the treatment with steroidogenesis inhibitors is normalization of cortisol production allowing the improvement of comorbidities (1). Most studies dealing with currently available steroidogenesis inhibitors used as monotherapy reported an overall antisecretory efficacy of roughly 50% in CS. Steroidogenesis inhibitors can be combined to better control hypercortisolism. To the best of our knowledge, we report here for the first time a patient treated with a ketoconazole–osilodrostat combination therapy.

Case presentation

Here, we report the case of Mr D.M., 53-years old, diagnosed with adrenocorticotrophic hormone (ACTH)-independent CS 6 months earlier. At diagnosis, he presented with resistant hypertension, hypokalemia, diabetes mellitus, easy bruising, purple abdominal striae and major oedema of the lower limbs.

Investigations

A biological assessment was performed, and the serum cortisol levels are depicted in Table 1. ACTH levels were suppressed (mean levels 1 pg/mL). Mean late-night salivary cortisol showed a four-fold increase (Table 2), and mean 24 h-urinary cortisol showed a two-fold increase. Serum cortisol was 1000 nmol/L at 08:00 h after 1 mg dexamethasone dose at 23:00 h. The rest of the adrenal hormonal workup was within normal ranges (aldosterone: 275 pmol/L and renin: 15 mIU/L). An adrenal CT was performed (Fig. 1) and exhibited a 70-mm left adrenal mass (spontaneous density: 5 HU and relative washout: 65%) and a 45-mm right adrenal mass (spontaneous density: −2 HU and relative washout: 75%). The case was discussed in a multidisciplinary team meeting, which advised to perform 18F-FDG PET-CT and 123I-Iodocholesterol scintigraphy before considering surgery. A genetic screening was performed, testing for ARMC5 and PRKAR1A pathogenic variants.

Figure 1View Full Size
Figure 1
Adrenal CT depicting the bilateral macronodular adrenocortical hyperplasia.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2021, 1; 10.1530/EDM-21-0071

Table 1Serum cortisol levels at diagnosis (A), using ketoconazole monotherapy (B), using osilodrostat monotherapy (C) and using osilodrostat–ketoconazole combination therapy (D).

Serum cortisol (nmol/L) 08:00 h 24:00 h 16:00 h 20:00 h 12:00 h 16:00 h
A. At diagnosis 660 615 716 566 541 561
B. Ketoconazole monotherapy 741 545 502 224 242 508
C. Osilodrostat monotherapy 658 637 588 672 486 692
D. Osilodrostat–ketoconazole combination 436 172 154 103 135 274
Table 2Salivary cortisol levels at diagnosis (A), using ketoconazole monotherapy (B), using osilodrostat monotherapy (C) and using osilodrostat-ketoconazole combination therapy (D).

Salivary cortisol (nmol/L) 23:00 h 12:00 h 13:00 h Mean
A. At diagnosis 47 62 38 49
B. Ketoconazole monotherapy 20 15 21 18
C. Osilodrostat monotherapy 85 90 56 77
D. Osilodrostat–ketoconazole combination 10 14 9 11

Treatment

As this condition occurred during the COVID-19 pandemic, it was decided to first initiate steroidogenesis inhibitors to lower the patient’s cortisol levels. Initially, ketoconazole was initiated and uptitrated up to 1000 mg per day based on close serum cortisol monitoring, with a three-fold increase of liver enzymes and poor control of cortisol levels (Table 1). In the absence of biological efficacy, ketoconazole was replaced by osilodrostat, which was gradually increased up to 30 mg per day (10 mg at 08:00 h and 20 mg at 20:00 h) without reaching normal cortisol levels (Table 1) and with slightly increased blood pressure levels. Considering the lack of efficacy of anticortisolic drugs used as monotherapy, we combined osilodrostat (30 mg per day) to ketoconazole (600 mg per day), that is, at the last maximal tolerated dose as monotherapy of each drug.

Outcome

This combination of steroidogenesis inhibitors achieved a good control in cortisol levels, mimicking a physiological circadian rhythm (Table 1D). The patient did not exhibit any side effect and the control of cortisol levels resulted in a rapid improvement of hypertension, kalemia, diabetes control and disappearance of lower limbs oedema. The patient underwent a 18F-FDG PET-CT that did not exhibit any increased uptake in both adrenal masses and a 123I-Iodocholesterol scintigraphy exhibiting a highly increased uptake in both adrenal masses, predominating in the left adrenal mass (70 mm). Unilateral adrenalectomy of the larger mass was then performed, and as the immediate post-operative serum cortisol level was 50 nmol/L, hydrocortisone was administered at a dose of 30 mg per day, with a stepwise decrease to 10 mg per day over 3 months. Pathological examination exhibited macronodular adrenal hyperplasia with a 70-mm adreno cortical adenoma (WEISS score: 1 and Ki67: 1%). The genetic screening exhibited a c.1908del p.(Phe637Leufs*6) variant of ARMC5 (pathogenic), located in exon 5. The patient has no offspring and is no longer in contact with the rest of his family.

Discussion

The goal of the treatment with steroidogenesis inhibitors is normalization of cortisol production allowing the improvement of comorbidities (1). Most studies dealing with currently available steroidogenesis inhibitors used as monotherapy reported an overall antisecretory efficacy of roughly 50% in CS. This rate of efficacy was probably underestimated in retrospective studies due to the lack of adequate uptitration of the dose; For example, the median dose reported in the French retrospective study on ketoconazole was only 800 mg/day, while 50% of the patients were uncontrolled at the last follow-up (2).

Steroidogenesis inhibitors can be combined to better control hypercortisolism. Up to now, such combinations, mainly ketoconazole and metyrapone, were mainly reported in patients with severe CS (median urinary-free Cortisol (UFC) 30- to 40-fold upper-limit norm (ULN)) and life-threatening comorbidities (3, 4). Normal UFC was reported in up to 86% of these patients treated with high doses of ketoconazole and metyrapone. Expected side effects (such as increased liver enzymes for ketoconazole or worsened hypertension and hypokalemia for metyrapone) were reported in the majority of the patients. The fear of these side effects probably explains the lack of uptitration in previous reports. Combination of steroidogenesis inhibitors has previously been described by Daniel et al. in the largest study reported on the use of metyrapone in CS; 29 patients were treated with metyrapone and ketoconazole or mitotane, including 22 in whom the second drug was added to metyrapone monotherapy because of partial efficacy or adverse effects. The final median metyrapone dose in patients controlled with combination therapy was 1500 mg per day (5).

Combination of adrenal steroidogenesis inhibitors should not be reserved to patients with severe hypercortisolism. In the case shown here, the association was highly effective in terms of secretion, using lower doses than those applied as a single treatment, but without the side effects previously observed with higher doses of each treatment used as a monotherapy. To our knowledge, the association of ketoconazole and osilodrostat had never been reported. Ketoconazole blocks several enzymes of the adrenal steroidogenesis such as CYP11A1, CYP17, CYP11B2 (aldosterone synthase) and CYP11B1 (11-hydroxylase), leading to decreased cortisol and occasionally testosterone concentrations. Though liver enzymes increase is not dose-dependent, it usually happens at doses exceeding 400–600 mg per day (2). Osilodrostat blocks CYP11B1 and CYP11B2; a combination should thus allow for a complete blockade of these enzymes that are necessary for cortisol secretion. Short-term side effects such as hypokalemia and hypertension are similar to those observed with metyrapone, due to increased levels of the precursor deoxycorticosterone, correlated with the dose of osilodrostat (6). As for our patient, the occurrence of side effects should not lead to immediately switch to another drug, but rather to decrease the dose and add another cortisol-lowering drug. Moreover, considering the current cost of newly-released drugs such a strategy could lower financial costs for patients and/or society.

Another point to take into account is the current COVID-19 pandemic, for which, as recently detailed in experts’ opinion (7), the main aim is to reach eucortisolism, whatever the way. Indeed patients presenting with CS usually also present with comorbidities such as obesity, hypertension, diabetes mellitus and immunodeficiency (8). Surgery, which represents the gold standard strategy in the management of CS (1, 9), might be delayed to reduce the hospital-associated risk of COVID-19, with post-surgical immunodepression and thromboembolic risks (7). Because immunosuppression and thromboembolic diathesis are common CS features (9, 10), during the COVID-19 pandemic, the use of steroidogenesis inhibitors appears of great interest. In these patients, combing steroidogenesis inhibitors at intermediate doses might allow for a rapid control of hypercortisolism without risks of major side effects if a single uptitrated treatment is not sufficient. Obviously, the management of associated comorbidities would also be crucial in this situation (11).

To conclude, we report for the first time a case of CS, in the context of primary bilateral macronodular adrenocortical hyperplasia successfully treated with a well-tolerated combination of ketoconazole and osilodrostat. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

Declaration of interest

F C and T B received research grants from Recordati Rare Disease and HRA Pharma Rare Diseases. Frederic Castinetti is on the editorial board of Endocrinology, Diabetes and Metabolism case reports. Frederic Castinetti was not involved in the review or editorial process for this paper, on which he is listed as an author.

Funding

This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Patient consent

Informed written consent has been obtained from the patient for publication of the case report.

Author contribution statement

V A was the patient’s physician involved in the clinical care and collected the data. T B and F C supervised the management of the patient. F C proposed the original idea of this case report. V A drafted the manuscript. F C critically reviewed the manuscript. T B revised the manuscript into its final version.

References

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7 Things Your Hair Reveals About Your Health

Posted on January 20, 2022 by MaryO

Your hair can tell you and your doctor if you are stressed, have a nutritional deficiency, thyroid problem, or other health issues. Here are seven key things to look for in your hair.

You probably think about your hair every day: worrying about a bad day, enjoying a good blow-dry, or wondering if you have to try the new style you noticed in your favorite celebrity. But you may be missing the clues your hair reveals about your health. Research shows that changes in the look, texture, or thickness of your hair can be signs of underlying health issues. Here’s how to tell if your hair changes are due to a health condition, genetics, stress, or a nutritional deficiency.

1 Stress (and genes) can cause you to turn gray

Anyone who has observed the hairstyle changes of a President of the Republic from one campaign to another has noticed that stress seems to cause hair to turn white. A mouse study published in the journal Nature suggests that chronic stress may actually contribute to white hair by causing DNA damage and reducing the number of pigment-producing cells in hair follicles. Stress can also lead to hair loss.

Another type of stress, known as oxidative stress, can also play a role in white hair. Oxidative stress can affect pigment-producing cells. Turning gray is actually a completely natural part of aging because hair follicles produce less color as you age. Your genes also play a role in when your hair turns gray. Ask your parents how old they were when they first saw the signs of silvering, and you might do the same. In fact, a study published in March 2016 in the journal Nature Communications was the first to identify the gene responsible for white hair.

2 brittle hair could be a sign of Cushing’s syndrome

Brittle hair is one of the symptoms of Cushing’s syndrome, which is a rare condition caused by excess cortisol, the main hormone body stress. But, there are many other, more obvious symptoms of Cushing’s syndrome, including high blood pressure, fatigue, and back pain. Treatment for Cushing’s syndrome may involve changing the dose of medication that may be causing the condition, such as glucocorticoids, which are steroids used to treat inflammation caused by various diseases.

3 Thinning hair may be a sign of thyroid disease

People with hypothyroidism, a condition that occurs when the thyroid gland does not produce enough thyroid hormones, may notice increased hair loss and change in hair appearance. About 4.6% of the population aged 12 years and older have hypothyroidism, although most cases are mild. Hypothyroidism can lead to thinning hair and other symptoms, such as fatigue, intolerance to cold, joint pain, muscle aches, puffy face and weight gain. A thyroid stimulating hormone (TSH) test can diagnose the condition, and treatment involves taking thyroid medication.

In addition to thinning hair, some thyroid disorders put you at risk for risk of autoimmune hair loss called alopecia areata. This type of hair loss causes round patches of sudden hair loss and is caused by the immune system attacking the hair follicles.

4 Hair loss can be a sign of anemia

If you suddenly notice a lot more hair in your hairbrush or on the floor of your shower, it may be a sign that your body has low iron stores, or anemia , and may warrant testing. This is another blood test we do when you complain of hair changes. Vegetarians or women with heavy periods increase their risk that hair changes are due to iron deficiency.

It is unclear why iron deficiency can lead to hair loss. hair, but iron is essential for many biological and chemical reactions, perhaps including hair growth. Hair loss can also occur (temporarily) with sudden changes in estrogen levels and is often noticed after pregnancy or stopping birth control pills.

5 The loss of hair could indicate protein deficiency

Protein is essential for hair health and growth (a lack of protein has been linked to hair thinning and hair loss ). Protein deficiency is not a problem for most people. Most adults need 0.8 grams of protein per kilogram of body weight. Good sources of protein include low-fat Greek yogurt, chickpeas, and chicken breast. People who have gastrointestinal difficulties or who have just had gastric bypass surgery may have problems digesting protein. These special situations will need to be managed with the help of your doctor. But most cases of thinning hair, even in women, are probably due to genetics.

6 White or yellow flakes can mean you have dandruff

Yellow or white flakes in your hair, on your shoulders and even in your eyebrows are a sign of dandruff, a chronic scalp condition. Dandruff is usually not a sign of a health problem and can be treated with specialized over-the-counter or prescription shampoos.

One of the most common causes of dandruff is a medical condition called seborrheic dermatitis. People with seborrheic dermatitis have red, oily skin covered in white or yellow scales. A yeast-like fungus called malassezia can also irritate the scalp. Insufficient shampoo, sensitivity to hair care products, and dry skin can also cause dandruff. (Dandruff is usually more severe in the winter, when indoor heating can make skin drier).

7 Damaged hair can mask other health issues

Although hair can reveal your condition, women more often complain about the damage caused by hair coloring and heat treatment. Excessive heat, from daily use of a flat iron or blow-drying, can certainly damage your hair, making it dry, brittle and difficult to maintain. Best not to use more than one hot tool per day (occasional double heat treatment is okay, but not daily). When applying heat to your hair, always use products with protective ingredients. Serums and shine drops tend to have hair-preserving qualities when using direct and indirect heat.

From https://www.mvdemocrat.com/appearance-texture-thickness-7-things-your-hair-reveals-about-your-health/

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‘Benign’ Adrenal Gland Tumors Might Cause Harm to Millions

Posted on January 8, 2022 by MaryO

Millions of people are at increased risk of type 2 diabetes and high blood pressure and don’t even know it, due to a hidden hormone problem in their bodies.

As many as 1 in 10 people have a non-cancerous tumor on one or both of their adrenal glands that could cause the gland to produce excess amounts of the stress hormone cortisol.

Up to now, doctors have thought that these tumors had little impact on your health.

But a new study out of Britain has found that up to half of people with these adrenal tumors are secreting enough excess cortisol to raise their risk of diabetes and high blood pressure.

Nearly 1.3 million adults in the United Kingdom alone could suffer from this disorder, which is called Mild Autonomous Cortisol Secretion (MACS), the researchers said.

Anyone found with one of these adrenal tumors should be screened to see if their health is at risk, said senior researcher Dr. Wiebke Arlt, director of the University of Birmingham Institute of Metabolism and Systems Research in England.

“People who are found to have an adrenal tumor should undergo assessment for cortisol excess and if they are found to suffer from cortisol overproduction they should be regularly screened for type 2 diabetes and hypertension and receive treatment if appropriate,” Arlt said.

These tumors are usually discovered during imaging scans of the abdomen to treat other illnesses, said Dr. André Lacroix, an endocrinologist at the University of Montreal Hospital Center, who wrote an editorial accompanying the study. Both were published Jan. 4 in the Annals of Internal Medicine.

Adrenal glands primarily produce the hormone adrenaline, but they are also responsible for the production of a number of other hormones, including cortisol, Lacroix said.

Cortisol is called the “fight-or-flight” hormone, and can cause blood sugar levels to rise and blood pressure to surge — usually in response to some perceived bodily threat.

Previous studies had indicated that about 1 in 3 adrenal tumors secrete excess cortisol, and an even lower number caused cortisol levels to rise so high that they affected health, researchers said in background notes.

But this new study of more than 1,300 people with adrenal tumors found that previous estimates were wrong.

About half of these patients had excess cortisol due to their adrenal tumors. Further, more than 15% had levels high enough to impact their health, compared to those with truly benign tumors.

MACS patients were more likely to be diagnosed with high blood pressure, and were as much as twice as likely to be on three or more blood pressure medications.

They also were more likely to have type 2 diabetes, and were twice as likely to require insulin to manage their blood sugar, the study found.

“This study clearly shows that mild cortisol production is more frequent than we thought before, and that the more cortisol you produce, the more likely to you are to have consequences such as diabetes and hypertension,” Lacroix said.

About 70% of people with MACS were women, and most were of postmenopausal age, the researchers said.

“Adrenal tumor-related cortisol excess is an important previously overlooked health issue that particularly affects women after the menopause,” Arlt said.

Lacroix agreed that guidelines should be changed so that people with adrenal tumors are regularly screened.

“Everybody who is found to have an adrenal nodule larger than 1 centimeter needs to be screened to see if they’re producing excess hormone or not,” he said. “That’s very clear.”

A number of medications can reduce cortisol overproduction or block cortisol action, if an adrenal tumor is found to be causing an excess of hormone.

People with severe cortisol excess can even have one of their two adrenal glands removed if necessary, Lacroix said.

“It is quite possible to live completely normally with one adrenal gland,” he said.

More information

The Cleveland Clinic has more about adrenal tumors.

SOURCES: Wiebke Arlt, MD, DSc, director, Institute of Metabolism and Systems Research, University of Birmingham, U.K.; André Lacroix, MD, endocrinologist, University of Montreal Hospital Center; Annals of Internal Medicine, Jan. 4, 2022

From https://consumer.healthday.com/1-4-benign-adrenal-gland-tumors-might-cause-harm-to-millions-2656172346.html

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No Synthetic Steroid Version of Korlym at This Time

Posted on December 11, 2021 by MaryO

Teva Pharmaceuticals suffered a fresh legal setback on Tuesday in its effort to market a generic version of the synthetic steroid Korlym to treat Cushing’s syndrome.

The Israeli drugmaker failed to convince the U.S. Court of Appeals for the Federal Circuit that the Patent Trial and Appeal Board improperly denied its bid to cancel a patent held by Corcept Therapeutics covering a method for using Korlym to treat the hormone disorder.

Menlo Park, California-based Corcept last year made over $353 million from sales of Korlym, the company’s only drug, according to a filing with the U.S. Securities and Exchange Commission.

Corcept’s patent relates to using a specific dose of Korlym’s active ingredient mifepristone and another drug to treat Cushing’s syndrome, which creates an excess of the hormone cortisol and causes high blood sugar, among other things.

Corcept sued Teva in New Jersey in 2018, alleging its proposed generic version of Korlym infringed the patent and others, in a case that is still ongoing. Teva asked the Patent Trial and Appeal Board to cancel the patent because earlier publications made it obvious that Corcept’s method would work to treat the disorder.

The board ruled for Corcept last year, and Teva appealed. Teva told the Federal Circuit that the PTAB held it to an improperly high standard for proving that the patent was invalid based on prior art.

Chief U.S. Circuit Judge Kimberly Moore, joined by Circuit Judges Pauline Newman and Jimmie Reyna, rejected Teva’s argument on Tuesday. Moore said the board found that a person of ordinary skill wouldn’t have reasonably expected Corcept’s treatment to be safe and effective before Corcept created it.

Moore also rejected Teva’s argument that the prior art disclosed a range of potential dosages that covered Corcept’s treatment.

Teva, Corcept and lawyers for the two companies didn’t immediately respond to requests for comment.

The case is Teva Pharmaceuticals USA Inc v. Corcept Therapeutics Inc, U.S. Court of Appeals for the Federal Circuit, No. 21-1360.

For Teva: John Rozendaal of Sterne Kessler Goldstein & Fox

For Corcept: Eric Stops of Quinn Emanuel Urquhart & Sullivan

From https://www.reuters.com/legal/transactional/teva-loses-bid-cancel-corcept-drug-patent-federal-circuit-2021-12-07/

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