No abstract

Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly.

ObjectiveSomapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed.Design26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939).MethodsMale or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9).ResultsMean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171).ConclusionsIn this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.

Cushing's syndrome (CS) is associated with low fat-free mass, but it is unclear whether hypercortisolism causes a loss of whole body protein. Body composition was studied prospectively in 15 patients with untreated CS (n = 14 pituitary adenoma; n = 1 adrenal adenoma), in 15 nonobese healthy controls, and in 15 weight-matched obese controls by 3 different methods: total body potassium counting (TBP), bioelectrical impedance analysis (BIA), and anthropometry. In 6 patients, body composition was studied before and within 6 months after pituitary surgery. In CS patients and weight-matched controls, body weight and total body fat were significantly higher than in nonobese controls. In CS patients, TBP was 18.4% lower than predicted, whereas in weight-matched controls TBP was 7.1% higher than predicted. As compared with nonobese and weight-matched controls, in CS patients TBP indicated a significant loss of body cell mass (BCM) of -20.2 and -21.1%, respectively. A significantly reduced arm muscle area of -21.3% compared with weight-matched controls also indicated a loss of whole body protein. In CS, however, BIA overestimated BCM when compared with TBP by +18% and agreement between BIA and TBP in the individual patient was poor (limits of agreement plus minus 27.6%), indicating the invalidity of standard BIA equations in this population. Measurements performed before and 6 months after successful pituitary surgery demonstrated a significant loss of body weight (-11%) and body fat (-33%), but BCM and muscle mass remained on a constant low level. In conclusion, this study shows that, in patients with CS, a significantly reduced BCM indicates a true protein loss. The second interesting finding is that in the early recovery after successful treatment of hypercortisolism patients lose body fat without gaining BCM or muscle mass.