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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

From http://www.medscape.com/viewarticle/878088

Filed under: pituitary, Treatments | Tagged: Growth Hormone Deficiency, pituitary, somapacitan, somavaratan |