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

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

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.


Aeterna Zentaris Inc.
Philip A. Theodore, 843-900-3211
Senior Vice President


Pediatric Endocrine Society Provides Guidance for Growth Hormone Use in Pediatric Patients

HealthDay News—Use of growth hormone in children and adolescents should be considered carefully, with assessment of the risks and benefits necessary for each patient, according to guidelines published in the January issue of Hormone Research in Paediatrics.

Adda Grimberg, MD, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues updated guidelines on the use of growth hormone, focusing on idiopathic short stature (ISS), GH deficiency (GHD), and primary insulin-like growth factor-I (IGF-I) deficiency (PIGFD). The guidelines were written on behalf of the Pediatric Endocrine Society.

The researchers recommend use of growth hormone for children and adolescents with GHD. Prospective recipients of growth hormone treatment should receive guidance regarding potential adverse effects and should be monitored for these effects. Parents and clinicians should take a shared decision-making approach to treating patients with ISS, and assess the physical and physiological burdens for the child, while considering the risks and benefits of treatment.Follow-up assessment of benefit and psychosocial impact should be conducted at 12 months after initiation and dose optimization of GH. IGF-I therapy is recommended for patients with severe PIGFD. Diagnosis of PIGFD/GH insensitivity syndrome should be based on a combination of factors that fall into four stages.

Physicians with expertise in managing endocrine disorders in children should provide consultation for evaluation of GHD-ISS-PIGFD and manage treatment.

“The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient,” the authors write. “In many instances, careful review highlights areas that need further research.”

Several authors disclosed financial ties to the pharmaceutical industry.


Grimberg A, DiVall SA, Polychronakos C, et al; on behalf of the Drug and Therapeutics Committee of the Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi: 10.1159/000452150


Growth Hormone Deficiency Following Complicated Mild Traumatic Brain Injury

Traumatic brain injury (“TBI”) is considered the main cause of hypopituitarism in adults and growth hormone (“GH”)deficiency is the most common pituitary deficit associated with TBI.

According to Cedars-Sinai, even after we stop growing, adults need growth hormone. Growth hormone plays a role in healthy muscle, how our bodies collect fat (especially around the stomach area), the ratio of high density to low density lipoproteins in cholesterol levels, and bone density. In addition, growth hormone is needed for normal brain function.

A recent study aimed to assess pituitary function and GH deficiency in adult patients at different time durations following complicated mild TBI, according to the Glasgow Coma Scale (GCS). The study also aimed to evaluate whether mild TBI patients with GH deficiency had developed alterations in the glycolipid profile.

Forty-eight patients (34 men and 14 women) with complicated mild TBI were included in the study. Twenty-three patients were evaluated at 1 year (Group A), and 25 patients at 5 years or longer after the injury (Group B). All patients underwent basal hormonal evaluation for pituitary function. GH deficiency was investigated by the combined test (GH releasing hormone + arginine). The glycolipid profile was also evaluated.

Researchers report that GH deficiency occurred in 8/23 patients (34.7 percent) of Group A and in 12/25 patients (48 percent) of Group B. In addition, two patients, one in each group, showed evidence of central hypothyroidism. Patients examined one-year or several years after complicated mild TBI had a similarly high occurrence of isolated GH deficiency, which was associated with visceral adiposity and metabolic alterations.

These findings suggest that patients with complicated mild TBI should be evaluated for GH deficiency even if several years have passed since the underlying trauma.


Longer-Acting Growth Hormones Promising for Adult GH Deficiency

Two investigational long-acting growth-hormone (GH) replacement products hold potential for less frequent dosing and improved adherence among adult patients with proven growth-hormone deficiency.

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

The new results, from a 26-week phase 3 trial of Novo Nordisk’s once-weekly growth-hormone derivative somapacitan and a dose-finding phase 2 safety study of Versartis’s long-acting recombinant growth hormone somavaratan, both in adult patients with growth-hormone deficiency, were presented here at ENDO 2017: The Endocrine Society Annual Meeting.

“Compliance is often a problem with daily growth-hormone injections in children and even with adults,” session moderator Luma Ghalib, MD, assistant professor in the division of endocrinology, diabetes, and metabolism at Ohio State University Wexner Medical Center, Columbus, told Medscape Medical News.

“Patients will often stop taking the daily medications, sometimes because of the cost but also because the daily injections are cumbersome. So the two longer-acting agents that have been studied will be an amazing breakthrough if they get [US FDA]-approved.”

But, she cautioned, longer-term data are needed. “In the long term, we worry about the metabolic effects. We know growth hormone can increase insulin resistance and diabetes, so we have to keep an eye on the peaks.”

And, she added, there could be a small risk for regrowth of the pituitary adenoma that caused the growth-hormone deficiency. “The risk will probably be slim because we haven’t seen regrowth with the daily dosing, but it hasn’t been studied.”

Once-Weekly Somapacitan Found Safe, Well-Tolerated

Gudmundur Johannsson, MD, PhD, professor and chief physician at the University of Gothenburg, Sweden, reported findings from the 26-week multicenter, multinational, randomized open-label parallel-group trial of somapacitan, a reversible albumin-binding human GH derivative intended for once-weekly subcutaneous administration.

A total of 92 adults (aged 18-79 years) who had been previously treated with once-daily growth-hormone replacement for at least 6 months were randomized 2:1 (after a 1-day washout) to either once-weekly somapacitan or once-daily somatropin (Norditropin, Novo Nordisk). Doses of both were titrated for the first 8 weeks to achieve normal insulinlike growth factor (IGF)-1 levels (target 0–2 standard deviation scores) and remained fixed for the subsequent 18 weeks.

Patients were around 50 years of age, 45% female, with body mass index 28 kg/m2. After remaining stable in both arms following titration, mean serum IGF-1 standard-deviation scores at week 25 were 0.22 for somapacitan and 0.35 for somatropin.

The primary outcome, incidence of adverse events including injection-site reactions, was similar between the two groups. Total adverse events occurred in 53 of 61 (86.9%) with somapacitan vs 21 of 31 (67.5%) with somatropin and included nasopharyngitis, headache, fatigue, dizziness, and arthralgia. Serious adverse events occurred in four (6.6%) with somapacitan and two (6.5%) with somatropin.

Of more than 1500 somapacitan injections given, there were two mild, transient, injection-site reactions (hematoma and bruising). No antibodies to somapacitan or GH were detected.

At week 26, patients’ scores on the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) for convenience, effectiveness, and satisfaction all favored somapacitan over somatropin.

Additional phase 3 trials in adults with growth-hormone deficiency are ongoing, as well as a phase 2 trial in children, a Novo Nordisk spokesperson told Medscape Medical News.

Somavaratan Dose-Finding Study Yields 2-Week Response

Kevin CJ Yuen, MD, MBChB, medical director of the Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, Washington, presented findings from an open-label, multicenter phase 2 study of somavaratan, a novel long-acting form of recombinant human growth hormone. The study aimed to evaluate starting dose, dose titration plan, and safety and to determine the IGF-1 response with 30-day dosing.

Patients were allocated into three starting dose cohorts: 0.6 mg/kg/month for those aged 35 and older, 0.8 mg/kg/month for those younger than 35, and 1.0 mg/kg/month for women on oral estrogen, regardless of age. All received five monthly subcutaneous doses of somavaratan with a target IGF-1 standard deviation score of 0–1.5. In all, 32 of 49 patients completed the study.

The most common adverse events were injection-site reactions (19.4%) and headache (11.1%), mostly mild or moderate. No severe adverse events were deemed related to somavaratan.

Mean IGF-I SDS increased from -1.32 at baseline to +2.31 at 7 days after the first dose, with subjects within each cohort who received higher doses tending to have higher IGF-1 responses. Following the last study dose, IGF-1 standard-deviation scores returned to baseline by day 22.

Thus, Dr Yuen said, twice-monthly administration will be studied going forward. Starting somavaratan dose and administration frequency are being investigated further in the extension study and then will be carried forward in a new phase 3 study.

Speaking about both products, Dr Ghalib told Medscape Medical News: “We are waiting. Less frequent dosing will make our lives and definitely the patients’ lives a lot easier.”

Dr Johannsson is a consultant and/or speaker for Viropharma, Shire, AstraZeneca, Novartis, Otsuka, Novo Nordisk, Merck, Serono, Pfizer, and Ipsen. Dr Yuen is an investigator and/or medical advisory board member for Pfizer, Opko, Novo Nordisk, Versartis, and Sandoz. Dr Ghalib has no relevant financial relationships.  

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ENDO 2017. April 1, 2017; Orlando, Florida. Abstract OR22-1, Abstract OR22-2


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