Weekly GH therapy may reduce treatment burden for adults with GH deficiency
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A once-weekly injection of the long-acting human growth hormone derivative somapacitan was associated with improvements in truncal and visceral fat and lean body mass that were similar to daily GH treatment among a cohort of adults with GH deficiency, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“The improvements were maintained at 86 weeks and treatment was well tolerated, with no unexpected safety concerns,” Gudmundur Johannsson, MD, PhD, professor in the department of internal medicine and clinical nutrition at the Sahlgrenska Academy, University of Gothenburg, Sweden, told Healio. “Somapacitan may provide an alternative to daily GH treatment for adults with GH deficiency, with the need for less-frequent injections expected to reduce burden of treatment and cause less interference with daily life.”
In a randomized, parallel-group trial conducted across 17 countries, Johannsson and colleagues analyzed data from 301 adults with GH deficiency (adult or childhood-onset) who were treatment-naive at baseline, randomly assigned once-weekly somapacitan (n = 121), daily GH (n = 119) or once-weekly placebo (n = 61) for 34 weeks (mean age, 45 years). During an open-label 52-week extension period, 272 participants continued treatment with somapacitan or daily GH; those receiving placebo were switched to somapacitan, and those receiving daily GH were randomly assigned to continue daily therapy or receive somapacitan. Body composition was measured by DXA at baseline and at the end of each treatment period. Primary endpoint was change in truncal fat percentage from baseline to 34 weeks. Dose titration was based on insulin-like growth factor I standard deviation score values.
At 34 weeks, researchers found that participants who received somapacitan experienced a mean –1.06% reduction in truncal fat percentage compared with a 0.47% increase among those assigned placebo, for an estimated difference of –1.53% (95% CI, –2.68 to –0.38). Those assigned somapacitan also experienced improvements in visceral fat, lean body mass and IGF-I standard deviation scores.
Improvements in body composition persisted at the end of the extension phase for participants who received somapacitan and daily GH. Adverse events did not differ between GH treatment groups.
“Despite the well-documented benefits of GH for this chronic condition, such as improved body composition, the need for daily GH injections — often on top of other hormonal replacement therapies — poses a barrier for many adults with GH deficiency,” Johannsson said. “A once-weekly GH treatment alternative could reduce the burden of treatment, leading to improved adherence and may lower the barrier to initiating and continuing replacement therapy.”
Johannsson said a phase 2 study with somapacitan has shown similar efficacy and safety compared with daily GH, and a confirmatory phase 3 trial among children with GH deficiency is ongoing, as well as a phase 2 trial among children born small for gestational age. – by Regina Schaffer
For more information:
Gudmundur Johannsson, MD, PhD, can be reached at gudmundur.johannsson@medic.gu.se.
Disclosures: Novo Nordisk funded this study. Johannsson reports he has received speaking fees from Eli Lilly, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Serono and Shire, and has been a consultant for AstraZeneca, Merck, Novo Nordisk, Pfizer, Serono and Shire. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Maria Fleseriu, MD, FACE
Growth hormone deficiency is recognized as an important component of hypopituitarism in adults; in addition to other hormones, many patients require GH replacement for variate periods of times. Patients frequently perceive the need for daily injection as a burden and sometimes even a limitation of starting the treatment. In this large international study, a once-weekly injection of GH has been compared with placebo for 34 weeks; the study had another group of patients who were randomized to the standard of care GH with a daily subcutaneous injection. During the extension phase, all participants received GH treatment for 52 weeks, either daily or the weekly somapacitan injection.
At the end of the main study at 34 weeks, somapacitan significantly reduced truncal fat vs. placebo and improved other body composition parameters, including visceral fat and lean body mass, and IGF-I. Somapacitan also increased appendicular skeletal muscle mass. Importantly, these effects were maintained at 86 weeks, which is essential to see for a long-term medication.
Somapacitan was well tolerated, and there were no new cases of diabetes. Adverse events, including injection-site reactions, were similar when compared with daily GH. Importantly for any new medication, no anti-somapacitan antibodies were detected. Bone parameters did not change during the study nor did lipid profile and some inflammatory markers. Unfortunately, the study did not have power to compare the daily vs. weekly injections.
Interestingly, the authors suggest, based on a post hoc analysis of women prescribed oral estrogen compared with all other participants, that women taking oral estrogen had less pronounced effects for some of the adipose tissue parameters. It is known that women with GH deficiency treated with oral estrogen require higher doses of GH — up to 30% — to achieve same IGF-I level, and it seems this holds true for the weekly preparation also.
The inclusion criteria in this study match well what we usually see in our pituitary clinics, thus results should apply also to patients with severe GH deficiency outside a clinical trial, too. The titration schedule for the weekly GH in the study was complex and needs to be fine-tuned for use by clinicians in a busy clinic.
In conclusion, a weekly rather than daily GH injection with similar efficacy and adverse events, although not directly compared in this study, should improve adherence to long- term, sometimes decades of, GH treatment. Further research and surveillance are needed to assess metabolism changes, potential effects of GH receptor polymorphisms on individual treatment responsiveness, risk of pituitary tumor growth with prolonged treatment as well as the optimal titration scheme and when is best to check the IGF-I after the injection.
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