Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

Doctors conducting the follow-up study of individuals treated with hGH looked at causes of death among recipients and found some disturbing news. Many more people have died from a treatable condition called adrenal crisis than from CJD (MaryO’Note: Creutzfeldt-Jakob Disease). This risk does not affect every recipient. It can affect those who lack other hormones in addition to growth hormone. Please read on to find out if this risk applies to you. Death from adrenal crisis can be prevented.

Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ACTH is responsible for regulating the adrenal gland. Often, people are unaware that they lack this hormone and therefore do not know about their risk of adrenal crisis.

Most people who were treated with hGH did not make enough of their own growth hormone. Some of them lacked growth hormone because they had birth defects, tumors or other diseases that cause the pituitary gland to malfunction or shut down. People with those problems frequently lack other key hormones made by the pituitary gland, such as ACTH, which directs the adrenal gland to make cortisol, a hormone necessary for life. Having too little cortisol can be fatal if not properly treated.

Treatment with hGH does not cause adrenal crisis, but because a number of people lacking growth hormone also lack ACTH, adrenal crisis has occurred in some people who were treated with hGH. In earlier updates we have talked about how adrenal crisis can be prevented, but people continue to die from adrenal crisis, which is brought on by lack of cortisol. These deaths can be prevented. Please talk to your doctor about whether you are at risk for adrenal crisis.

  • Why should people treated with hGH know about adrenal crisis? Among the people who received hGH, those who had birth defects, tumors, and other diseases affecting the brain lacked hGH and often, other hormones made by the pituitary gland. A shortage of the hormones that regulate the adrenal glands can cause many health problems. It can also lead to death from adrenal crisis. This tragedy can be prevented.
  • What are adrenal hormones? The pituitary gland makes many hormones, including growth hormone and ACTH, a hormone which signals the adrenal glands to make cortisol, a hormone needed for life. If the adrenal gland doesn’t make enough cortisol, replacement medications must be taken. The most common medicines used for cortisol replacement are:
    • Hydrocortisone
    • Prednisone
    • Dexamethasone
  • What is adrenal crisis? Adrenal hormones are needed for life. The system that pumps blood through the body cannot work during times of physical stress, such as illness or injury, if there is a severe lack of cortisol (or its replacement). People who lack cortisol must take their cortisol replacement medication on a regular basis, and when they are sick or injured, they must take extra cortisol replacement to prevent adrenal crisis. When there is not enough cortisol, adrenal crisis can occur and may rapidly lead to death.
  • What are the symptoms of lack of adrenal hormones? If you don’t have enough cortisol or its replacement, you may have some of these problems:
    • feeling weak
    • feeling tired all the time
    • feeling sick to your stomach
    • vomiting
    • no appetite
    • weight loss

    When someone with adrenal gland problems has weakness, nausea, or vomiting, that person needs immediate emergency treatment to prevent adrenal crisis and possible death.

  • Why are adrenal hormones so important? Cortisol (or its replacement) helps the body respond to stress from infection, injury, or surgery. The normal adrenal gland responds to serious illness by making up to 10 times more cortisol than it usually makes. It automatically makes as much as the body needs. If you are taking a cortisol replacement drug because your body cannot make these hormones, you must increase the cortisol replacement drugs during times of illness, injury, or surgery. Some people make enough cortisol for times when they feel well, but not enough to meet greater needs when they are ill or injured. Those people might not need cortisol replacement every day but may need to take cortisol replacement medication when their body is under stress. Adrenal crisis is extremely serious and can cause death if not treated promptly. Discuss this problem with your doctor to help decide whether you need more medication or other treatment to protect your health.
  • How is adrenal crisis treated? People with adrenal crisis need immediate treatment. Any delay can cause death. When people with adrenal crisis are vomiting or unconscious and cannot take medicine, the hormones can be given as an injection. Getting an injection of adrenal hormones can save your life if you are in adrenal crisis. If you lack the ability to make cortisol naturally, you should carry a medical ID card and wear a Medic-Alert bracelet to tell emergency workers that you lack adrenal hormones and need treatment. This precaution can save your life if you are sick or injured.
  • How can I prevent adrenal crisis?
    • If you are always tired, feel weak, and have lost weight, ask your doctor if you might have a shortage of adrenal hormones.
    • If you take hydrocortisone, prednisone, or dexamethasone, learn how to increase the dose when you become ill.
    • If you are very ill, especially if you are vomiting and cannot take pills, seek emergency medical care immediately. Make sure you have a hydrocortisone injection with you at all times, and make sure that you and those around you (in case you’re not conscious) know how and when to administer the injection.
    • Carry a medical ID card and wear a bracelet telling emergency workers that you have adrenal insufficiency and need cortisol. This way, they can treat you right away if you are injured.

Remember: Some people who lacked growth hormone may also lack cortisol, a hormone necessary for life. Lack of cortisol can cause adrenal crisis, a preventable condition that can cause death if treated improperly. Deaths from adrenal crisis can be prevented if patients and their families recognize the condition and are careful to treat it right away. Adrenal crisis is a medical emergency. Know the symptoms and how to adjust your medication when you are ill. Taking these precautions can save your life.

From https://www.niddk.nih.gov/health-information/endocrine-diseases/national-hormone-pituitary-program/health-alert-adrenal-crisis-causes-death-people-treated-hgh

Gene test for growth hormone deficiency developed

A new test developed by University of Manchester and NHS scientists could revolutionise the way children with growth hormone deficiency are diagnosed.

Children suspected of having GHD – which cause growth to slow down or stop and other serious physical problems—currently require a test involving fasting for up to 12 hours.

The fasting is followed by an intravenous infusion in hospital and up to 10 blood tests over half a day to measure growth hormone production.

Because the current test is unreliable, it often has to be done twice before growth hormone injections can be prescribed.

Now the discovery—which the team think could be available within 2 to 5 years -could reduce the process to a single blood test, freeing up valuable time and space for the NHS.

Dr. Adam Stevens from The University of Manchester and Dr. Philip Murray from Manchester University NHS Foundation Trust, were part of the team whose results are published in JCI Insight today.

Dr. Stevens said: “We think this is an important development in the way doctors will be able to diagnose growth hormone deficiency – a condition which causes distress to many thousands of children in the UK

“This sort of diagnostic would not be available even a few years ago but thanks to the enormous computing power we have, and advances in genetics, it is now possible for this aspect of care to be made so much easier for patients – and the NHS.

“These volume of data involved is so huge and complicated that traditional data-processing application software is inadequate to deal with it.”

Comparing data from 72 patients with GHD and 26 healthy children, they used high powered computers to examine 30,000 genes—the full gene expression- of each child.

A sophisticated mathematical technique called Random Forest Analysis analysed around three million separate data points to compare different gene patterns between the children with and without GHD.

The research identified 347 genes which when analysed with the computer algorithm can determine whether a child has GHD or not and thus whether they will benefit from treatment.

Growth hormone deficiency (GHD) occurs when the pituitary gland—which is size of a pea- fails to produce enough growth hormone. It more commonly affects children than adults.

Many teenagers with GHD have poor bone strength, fatigue and lack stamina as well as depression, lack of concentration, poor memory and anxiety problems.

GHD occurs in roughly 1 in 5,000 people. Since the mid-1980s, synthetic growth hormones have been successfully used to treat children—and adults—with the deficiency.

Dr. Murray added: “This study provides strong proof of concept, but before it is in a position to be adopted by the NHS, we must carry out a further validation exercise which will involve comparing our new diagnostic with the existing test.

“Once we have crossed that hurdle, we hope to be in a position for this to be adopted within 2 to 5 years – and that can’t come soon enough for these children.”

Child Growth Foundation manager Jenny Child’s daughter has Growth Hormone Deficiency.

She said: Growth Hormone Deficiency isn’t just about growth, as lack of growth hormone impacts the child in many ways, such as lack of strength and they can find it difficult to keep up physically with their peers. It impacts the child’s self-esteem as they are often treated as being much younger, because of their size. Growth hormone treatment allows the child to grow to their genetic potential.

“A growth hormone stimulation test can be very daunting for both child and parents. The test can make the child feel quite unwell and they can experience headaches, nausea and unconsciousness through hypoglycaemia.”

 Explore further: Northern climes make a difference with growth hormone treatment

More information: Philip G. Murray et al. Transcriptomics and machine learning predict diagnosis and severity of growth hormone deficiency, JCI Insight (2018). DOI: 10.1172/jci.insight.93247

Oral Test for Adult Growth Hormone Deficiency Approved in US

The US Food and Drug Administration (FDA) has approved an orally available ghrelin agonistmacimorelin (Macrilen, Aeterna Zentaris), to be used in the diagnosis of patients with adult growth-hormone deficiency (AGHD).

Macimorelin stimulates the secretion of growth hormone from the pituitary gland into the circulatory system. Stimulated growth-hormone levels are measured in four blood samples over 90 minutes after oral administration of the agent for the assessment of growth-hormone deficiency.

Prior to the approval of macimorelin, the historical gold standard for evaluation of adult growth-hormone deficiency was the insulin tolerance test (ITT), an intravenous test requiring many blood draws over several hours.

The ITT procedure is inconvenient for patients and medical practitioners and is contraindicated in some patients, such as those with coronary heart disease or seizure disorder, because it requires the patient to experience hypoglycemia to obtain an accurate result.

Adult growth-hormone deficiency is a rare disorder characterized by the inadequate secretion of growth hormone from the pituitary gland. It can be hereditary; acquired as a result of trauma, infection, radiation therapy, or brain tumor growth; or can even emerge without a diagnosable cause. Currently, it is treated with once-daily injections of subcutaneous growth hormone.

“Clinical studies have demonstrated that growth-hormone stimulation testing for adult growth-hormone deficiency with oral…macimorelin is reliable, well-tolerated, reproducible, and safe and a much simpler test to conduct than currently available options,” said Kevin Yuen, MD, clinical investigator and neuroendocrinologist, Barrow Neurological Institute, and medical director of the Barrow Neuroendocrinology Clinic, Phoenix, Arizona, in a press release issued by Aeterna Zentaris.

“The availability of…macimorelin will greatly relieve the burden of endocrinologists in reliably and accurately diagnosing adult growth-hormone deficiency,” he added.

Aeterna Zentaris estimates that approximately 60,000 tests for suspected adult growth-hormone deficiency are conducted each year across the United States, Canada, and Europe.

“In the absence of an FDA-approved diagnostic test for adult growth-hormone deficiency, Macrilen fills an important gap and addresses a medical need for a convenient test that will better serve patients and health providers,” said Michael V Ward, chief executive officer, Aeterna Zentaris.

Macrilen is expected to be launched in the United States during the first quarter of 2018.

It is also awaiting approval in the European Union.

Follow Lisa Nainggolan on Twitter: @lisanainggolan1. For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

From https://www.medscape.com/viewarticle/890457

Growth Hormone: Drug companies are growing less generous in helping patients pay for meds

For 14 years, Encino resident Ed Wright received an expensive prescription medication for free through a drug-industry program intended to assist people with limited or fixed incomes.

Now he’s rationing his doses after a change to the program that imposed a $1,100 deductible before he can get a refill.

“I can’t afford that,” Wright, 75, told me. “When I run out in a few weeks, that’s going to be it.”

He isn’t alone. Industry watchers say soaring drug prices have prompted many pharmaceutical companies to rethink long-standing programs to help subsidize purchases or even give meds away for free.

“More and more people have become aware of these programs, and demand has gone up,” said David P. Wilson, president of PRAM Insurance Services, a Brea firm that helps employers with prescription-drug benefits.

This means trouble for patients who, like Wright, can’t handle sticker shock at the drugstore.

He suffered a head injury 17 years ago that damaged his pituitary gland. In 2003, he was diagnosed as having an abnormally low level of growth hormone, which caused him to suddenly become overwhelmed with fatigue.

That’s a potentially life-threatening condition if an episode should occur while driving, walking down stairs or performing some other physical activity.

Wright’s doctor prescribed the self-injected human growth hormone Humatrope, manufactured by Eli Lilly & Co.

The cost, however, was out of reach for Wright, even with Medicare Part D. According to the drug-pricing website GoodRX, a 6-milligram cartridge of Humatrope — a one month’s supply — runs about $700.

Luckily, Wright’s fixed income made him eligible for a program called Lilly Cares, which made the drug available free of charge. He and his doctor would renew the paperwork annually, and for 14 years Wright had no difficulty receiving the med.

That’s no longer the case with the new $1,100 deductible, which requires Wright to spend that amount on prescription drugs before he can access his free Humatrope.

Wright requires few other drugs, so the deductible is an almost insurmountable barrier to maintaining normal quality of life.

Most drugmakers offer what are known as patient assistance programs, through which the company may provide meds directly to patients at little or no cost. Or the company may assist with co-payments — the patient’s out-of-pocket expense that’s not covered by an insurer.

2009 study published in the journal Health Affairs found that most patient assistance programs run by drug companies were reluctant to disclose details of the number of people they serve or the program’s eligibility requirements.

These programs “exist to provide patients with access to a wide variety of medications,” researchers concluded. However, “many details about these programs remain unclear. As a result, the extent to which these programs provide a safety net to patients is poorly understood.”

Aaron Tidball, chief Medicare advisor for the Illinois consulting firm Allsup, which assists individuals and businesses in navigating the public insurance system, said Lilly Cares “has been more generous than some programs we’ve seen.”

He said that, until now, people who qualified for Lilly’s assistance were able to receive whatever specialty meds that were prescribed by their doctor without cost or co-pay.

It should be noted, though, that Lilly has structured its program so the company benefits as well. Rather than provide drugs directly to patients, as many companies do, Lilly donates its medications to a private foundation, the Lilly Cares Foundation, which in turn deals with the public.

This allows Lilly to deduct the value of its donated drugs from its taxes. According to the nonprofit foundation’s 2015 tax return, which by law must be made public, the Lilly Cares Foundation received more than $408 million worth of drugs from the company. That figure represented the “fair market value” of the meds.

“That’s obviously a lot more than the cost to produce the drugs,” observed Jeff Geida, a Los Angeles estate lawyer who specializes in nonprofit foundations and who examined the most recent Lilly Cares tax return at my request.

In other words, Lilly was able to reduce its taxable income for the year by $408 million, although the actual expense of manufacturing the donated drugs almost certainly was just a fraction of the deducted amount.

“It’s a very good deal,” Geida said.

To be sure, the company is still doing enormous good by making millions of dollars worth of drugs available to people in need. But the inflated figures highlight the lack of transparency surrounding the true cost of prescription meds.

Julie Williams, a Lilly spokeswoman, declined to answer my questions about the Lilly Cares Foundation. But she forwarded a statement from Steven Stapleton, the foundation’s president.

He said the foundation imposed the $1,100 deductible for Medicare Part D beneficiaries “after benchmarking our program with other similar programs, helping Lilly Cares to balance all the criteria for the program and to try to help as many people as possible.”

That’s just gibberish to my ear — and doesn’t address the fact that Lilly still helps itself to that whopping tax deduction while making it considerably harder for low-income people to receive assistance.

I called the foundation and spoke with a service rep, but she said she didn’t know why the deductible was put in place. Nor could she explain how it’s in the best interest of patients with limited incomes to have to spend $1,100 on drugs before being eligible to receive a needed medicine.

Stapleton said notifications were sent to program participants in the fall of 2015 and 2016, but Wright told me he couldn’t recall receiving any such notice. The office manager of his doctor’s practice said she too was caught by surprise.

Lilly Cares made the situation even more inexplicable when it sent a notice to Wright last month formally dropping him from the program. The only reason it gave was “inactivity,” which made no sense considering that he’s been using Humatrope steadily for 14 years.

Williams, the Lilly spokeswoman, said she couldn’t discuss an individual patient.

Wright told me that, after I started poking around, he received a call from a Lilly representative. She advised him to contact the Partnership for Prescription Assistance, an industry-sponsored service intended to help people find subsidy programs that can help cover the high cost of their meds.

Wright contacted four subsidy programs through the service. Each one turned him down.

Lilly says it’s balancing all the criteria for Lilly Cares, which undoubtedly will make the company more profitable.

Wright, and the many other patients in similar positions, are a secondary consideration.

From http://www.latimes.com/business/lazarus/la-fi-lazarus-prescription-drug-assistance-20170815-story.html

NDA for Macrilen™ for the Evaluation of Growth Hormone Deficiency in Adults

CHARLESTON, S.C.–(BUSINESS WIRE)–Aeterna Zentaris Inc. (NASDAQ: AEZS)(TSX: AEZS) (the “Company”) today announced that it has been notified by the U.S. Food and Drug Administration (“FDA”), that the Company’s New Drug Application (“NDA”) seeking approval of Macrilen™ (macimorelin) for the evaluation of growth hormone deficiency in adults (“AGHD”) has been accepted as a complete response to the FDA’s November 5, 2014 Complete Response Letter and granted a PDUFA date of December 30, 2017.

David A. Dodd, President and Chief Executive Officer of the Company stated, “We are pleased that the FDA has formally accepted our resubmitted NDA and that it is under active review with an end-of-year PDUFA date. We remain confident that the FDA will approve our NDA and, therefore, we are moving forward with our preparations to launch the product in the first quarter of 2018.”

The Company also announces that Mr. Kenneth Newport is no longer a member of the Board of Directors effective as of July 12, 2017.

About MacrilenTM (macimorelin)

Macimorelin, a ghrelin agonist, is an orally-active small molecule that stimulates the secretion of growth hormone. Macimorelin has been granted orphan drug designation by the FDA for diagnosis of AGHD. The Company owns the worldwide rights to this patented compound and has significant patent protection left. The Company’s U.S. composition of matter patent expires in 2022 and its U.S. utility patent runs through 2027. The Company proposes, subject to FDA approval, to market macimorelin under the tradename Macrilen™.

About AGHD

AGHD affects approximately 75,000 adults across the U.S., Canada and Europe. Growth hormone not only plays an important role in growth from childhood to adulthood, but also helps promote a hormonally-balanced health status. AGHD mostly results from damage to the pituitary gland. It is usually characterized by a reduction in bone mineral density, lean body mass, exercise capacity, and overall quality of life as well as an increase of cardiovascular risks.

About Aeterna Zentaris Inc.

Aeterna Zentaris is a specialty biopharmaceutical company engaged in developing and commercializing novel pharmaceutical therapies. We are engaged in drug development activities and in the promotion of products for others. We recently completed Phase 3 studies of two internally developed compounds. The focus of our business development efforts is the acquisition of licenses to products that are relevant to our therapeutic areas of focus. We also intend to license out certain commercial rights of internally developed products to licensees in non-U.S. territories where such out-licensing would enable us to ensure development, registration and launch of our product candidates. Our goal is to become a growth-oriented specialty biopharmaceutical company by pursuing successful development and commercialization of our product portfolio, achieving successful commercial presence and growth, while consistently delivering value to our shareholders, employees and the medical providers and patients who will benefit from our products. For more information, visit www.aezsinc.com.

Forward-Looking Statements

This press release contains forward-looking statements made pursuant to the safe harbor provision of the U.S. Securities Litigation Reform Act of 1995, which reflect our current expectations regarding future events. Forward-looking statements may include, but are not limited to statements preceded by, followed by, or that include the words “expects,” “believes,” “intends,” “anticipates,” and similar terms that relate to future events, performance, or our results. Forward-looking statements involve known risks and uncertainties, many of which are discussed under the caption “Key Information – Risk Factors” in our most recent Annual Report on Form 20-F filed with the relevant Canadian securities regulatory authorities in lieu of an annual information form and with the U.S. Securities and Exchange Commission (“SEC”). Such statements include, but are not limited to, statements about the progress of our research, development and clinical trials and the timing of, and prospects for, regulatory approval and commercialization of our product candidates, the timing of expected results of our studies, anticipated results of these studies, statements about the status of our efforts to establish a commercial operation and to obtain the right to promote or sell products that we did not develop and estimates regarding our capital requirements and our needs for, and our ability to obtain, additional financing. Known and unknown risks and uncertainties could cause our actual results to differ materially from those in forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue our research and development projects and clinical trials, the successful and timely completion of clinical studies, the risk that safety and efficacy data from any of our Phase 3 trials may not coincide with the data analyses from previously reported Phase 1 and/or Phase 2 clinical trials, the rejection or non-acceptance of any new drug application by one or more regulatory authorities and, more generally, uncertainties related to the regulatory process (including whether or not the regulatory authorities will definitively accept the Company’s conclusions regarding Macrilen™ and approve its registration following the Company’s re-submission of an NDA for the product as described elsewhere in this press release), the ability of the Company to efficiently commercialize one or more of its products or product candidates, the degree of market acceptance once our products are approved for commercialization, our ability to take advantage of business opportunities in the pharmaceutical industry, our ability to protect our intellectual property, and the potential of liability arising from shareholder lawsuits and general changes in economic conditions. Investors should consult the Company’s quarterly and annual filings with the Canadian securities commissions and the SEC for additional information on risks and uncertainties. Given these uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law.

Contacts

Aeterna Zentaris Inc.
Philip A. Theodore, 843-900-3211
Senior Vice President
ir@aezsinc.com

From http://www.businesswire.com/news/home/20170718006321/en/NDA-Macrilen%E2%84%A2-Evaluation-Growth-Hormone-Deficiency-Adults

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