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

Bimonthly Growth Hormone Injections to Replace Daily Injections?

At the Annual ENDO 2017 meeting in Orlando, FL, Moore et al provided an update on somavaratan, the long acting recombinant human growth hormone being investigated for children and adults with growth hormone deficiency.

Current treatment for these patients is somewhat burdensome given the need for daily subcutaneous injections. Somavaratan provides the option for bimonthly injections.

At ENDO 2017, 3 year data was presented in children given somavaratan and the data is impressive.

The 3 year data is part of an ongoing extension study following a 6 month Phase 2 trial in which 64 patients received 5.0 mg/kg/month at various dosing schedules. Of those patients, 60 continued in an open label extension study (dose adjusted to 3.5 mg/kg given twice-monthly by the beginning of Year 2 of treatment).  At ENDO 2017, data from 30 of those patients who had completed 3 years of treatment were presented.

(Insulin-like growth factor standard deviation score (IGF-I SDS) increased from -1.7 ± 0.8 at baseline to 1.1 ± 1.6 at peak (3–5 days post-injection) and -0.2 ± 0.9 at trough (end of dosing cycle) in Year 3. Of the 30 patients, 8 had transient IGF-I SDS excursions > 2.0, of which 3 events were > 3.0 (range, 2.3–3.9).

Height velocity (HV) remained consistent at 8.5 ± 1.8, 8.5 ± 1.7, and 8.1 ± 1.5 cm/year, for years 1, 2, and 3 respectively.

Height-SDS increased from -2.6 ± 0.5 at baseline to -1.9 ± 0.6, -1.4 ± 0.7, and -1.0 ± 0.7 at years 1, 2, and 3, respectively.

Treatment-related adverse events were generally mild and transient.

In an exclusive interview with Rare Disease Report, one of the investigators of the study, Bradley Miller, MD, PhD, of the University of Minnesota Masonic Children’s Hospital, said that compliance is an issue with growth hormone replacement therapy and any options that can remove the daily injection requirements would likely be well received by both patients and clinicians.

A Phase 3 study is currently underway to comparing bimonthly somavaratan treatment with daily growth hormone treatments (NCT02339090).

Somavaratan is being developed by Versartis Inc

About Growth Hormone Deficiency 

Growth hormone deficiency occurs when the pituitary gland does not produce enough growth hormone, resulting in short stature, delayed or absent puberty, and changes in muscle mass, cholesterol levels, and bone strength. The condition can be congenital, structural (malformations in the brain) or acquired (resulting from trauma, infections, tumors, radiation therapy, or other causes).

Currently, the standard of care is subcutaneous injection of a biosynthetic recombinant human growth hormone (rhGH). The frequency of the injections is based on the patient’s level of growth hormone deficiency (ie, whether growth hormone is completely absent or some growth hormone is present), but most patients require daily administration.

The rhGH treatments are typically given until the child’s maximum growth potential is achieved, often requiring many years of treatment (and increasing the risk of poor compliance).

Reference

Moore WV, Fechner PY, Nguyan HJ, et al. Safety and Efficacy of Somavaratan (VRS-317), a Long-Acting Recombinant Human Growth Hormone (rhGH), in Children with Growth Hormone Deficiency (GHD): 3-Year Update of the Vertical & VISTA Trials (NCT01718041, NCT02068521). Presented at: ENDO 2017; Orlando, FL; April 1-4, 2017. Abstract OE31-1.

From http://www.raredr.com/news/bimonthly-growth-hormone

Signs and Symptoms of Adult Growth Hormone Deficiency

Major Symptoms of Adult-Onset Growth Hormone deficiency

You may be wondering if the unusual symptoms you are feeling lately may be due to growth hormone deficiency. Growth hormone is now widely recognized as an important factor in the maintenance of health and well-being. However, research shows that most people won’t experience the debilitating effects of growth hormone deficiency during their lifetime as the condition is not a cause of aging but rather serious illness or injury. If you want to learn about growth hormone deficiency signs and symptoms and what clinics like the Nexel Medical can do about this problem, keep reading.

About growth hormone deficiency in children

Growth hormone deficiency manifests differently in childhood than it does in adulthood. For normal development, there needs to be an adequate amount of circulating growth hormones in the body. The main symptom of growth hormone deficiency in children is stunted growth and developmental problems. This is a result of insufficient amounts of this important hormone in the body that is normally secreted by the pituitary gland. The pituitary gland is a small gland located at the bottom of the hypothalamus, at the base of the brain. Any damage to the pituitary gland will cause a drop in growth hormone levels that could be dangerous for children.

Growth hormone deficiency in adults

Although it would be natural to assume that there is no need for a growth hormone in the body once the growth process is over and we’ve reached adult height and weight, this is simply not the case. The human growth hormone plays a vital role in overall health up until old age. Damage to the pituitary gland from tumors is the most common cause of growth hormone deficiency in adults. People also tend to experience a decline in growth hormone levels that naturally come with age, but researchers agree that this decline is insignificant and shouldn’t cause any problems. However, damage to the pituitary gland will definitely cause major symptoms that require immediate treatment from clinics such as the Nexel Medical. According to an article published in the Indian Journal of Endocrinology and Metabolism, growth hormone deficiency has been associated with abnormalities of:

  • Neuropsychiatric and cognitive functioning

  • Cardiovascular functioning

  • The neuromuscular system

  • The skeletal system

Metabolic functioning

All these problems can be significantly reversed with growth hormone therapy. Growth hormone is now widely recognized as a hormone playing a role in the regulation of body composition, energy levels, and normal mental functioning.

Causes and symptoms of growth hormone deficiency

According to current research, 65% of all cases of growth hormone deficiency are caused by pituitary tumors. Other common causes are infections of the pituitary gland, pituitary hemorrhage, and idiopathic growth hormone deficiency. Traumatic brain injury may also lead to growth hormone deficiency in some cases. The clinical features or signs and symptoms of growth hormone deficiency are many and may seem unspecific at first. Those suspecting problems with the pituitary gland and growth hormone deficiency should look out for the following:

  • Cognitive changes (memory, processing, speed, attention)

  • Mood changes (depression, anxiety)

  • Social withdrawal

  • Fatigue and lack of strength

  • Neuromuscular dysfunction

  • Decreased bone mineral density

  • Decreased sweating

  • Weight gain and muscle loss

  • Metabolic changes (insulin resistance, dyslipidemia)

  • Treatment of growth hormone deficiency

Growth hormone deficiency in adults is usually treated with growth hormone replacement therapy. The hormone is in such cases administered intravenously or through dermal implants. A study published in the Journal of Clinical Endocrinology and Metabolism found that administering growth hormone to patients with growth hormone deficiency resulted in a reduction of visceral body fat by 30%. The researchers also noticed an improvement in bone metabolism and a decline in psychiatric complaints in these patients.

Why growth hormone pills don’t work?

Taking oral supplements claiming to contain the human growth hormone won’t work simply because the majority of it will be digested by your gastrointestinal tract before it gets the chance to reach your bloodstream. This is mainly because the human growth hormone is a protein and all proteins are broken down by the digestive tract. This was confirmed by studies as stated in an FDA-published article explaining how growth hormone administered to dairy cows cannot affect humans.

Conclusion

The human growth hormone is an important hormone for the maintenance of health, metabolism, and mental functioning. Studies on growth hormone deficiency show that most people have adequate levels of this hormone in their bodies. Although a decline in growth hormone levels comes with age, this decline is not enough to cause major changes in a person’s health and well-being. On the other hand, structural damage to the pituitary gland will cause some of the major conditions and symptoms of growth hormone deficiency. In such cases, growth hormone replacement therapy is highly advised. Clinics such as Nexel Medical are among many that offer different hormone replacement therapies including for growth hormone deficiencies.

References

Hormone Replacement Therapy Clinic

http://www.ncbi.nlm.nih.gov/pubmed/23435439

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183535/

http://www.ncbi.nlm.nih.gov/pubmed/19001512

http://www.ncbi.nlm.nih.gov/pubmed/8432773

http://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm130321.htm

From http://theinscribermag.com/health-fitness/signs-and-symptoms-of-adult-growth-hormone-deficiency.html

GH therapy increases fracture risk in patients previously treated for acromegaly

van Varsseveld NC, et al. Pituitary. 2016;doi:10.1007/s11102-016-0716-3.

Adult patients with severe growth hormone deficiency previously treated for acromegaly saw an increased fracture risk after 6 years of growth hormone replacement therapy, whereas those previously treated for Cushing’s disease did not experience the same risk, according to a recent observational study.

Nadege C. van Varsseveld, MD, of the department of internal medicine at VU University Medical Center in Amsterdam, and colleagues analyzed data from 1,028 patients with previous nonfunctioning pituitary adenoma (NFPA; n = 783), acromegaly (n = 65) and Cushing’s disease (n = 180), identified through the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide, long-term surveillance study in patients with severe GH deficiency. Data were collected biannually from medical records through 2009. Baseline DXA measurements were available for 414 patients; 71 (17.1%) had osteoporosis at one or more of the measured sites; 147 (35.5%) had osteopenia.

During a mean follow-up of 5.2 years, researchers found that 166 of patients with previous NFPA were prescribed osteoporosis medications (21.3%), as were 69 patients with previous Cushing’s disease (38.5%) and 22 patients with previous acromegaly (33.4%). During follow-up, 39 patients experienced fractures (3.8%; 32 experiencing one fracture), including 26 patients in the previous NFPA group, eight patients in the previous Cushing’s disease group and five patients in the previous acromegaly group. The median time between baseline and first fracture was 2.4 years (mean age, 59 years).

Researchers found that fracture risk did not differ between groups before 6 years’ follow-up. Fracture risk increased in patients with previous acromegaly after 6 years’ follow-up, but not for those with previous Cushing’s disease vs. patients with NFPA. Results persisted after adjustment for multiple factors, including sex, age, fracture history and the extent of pituitary insufficiency.

The researchers noted that patients with previous Cushing’s disease were younger and more often women and had a greater history of osteopenia or osteoporosis, whereas patients with acromegaly had a longer duration between tumor treatment and the start of GH therapy and were treated more often with radiotherapy.

“During active acromegaly, increased bone turnover has been observed, but reported effects on [bone mineral density] are heterogeneous,” the researchers wrote. “It is postulated that cortical BMD increases, whereas trabecular BMD decreases or remains unaffected.

“The increased fracture risk in the present study may be a long-term effect of impaired skeletal health due to previous GH excess, even though this was not reflected by an increased occurrence of osteopenia or osteoporosis in the medical history,” the researchers wrote. – by Regina Schaffer

Disclosure: One researcher reports receiving consultancy fees from Novartis and Pfizer.

From http://www.healio.com/endocrinology/hormone-therapy/news/online/%7B92a67ad7-3bd5-46f0-b999-0a8e3486edab%7D/gh-therapy-increases-fracture-risk-in-patients-previously-treated-for-acromegaly

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