Guidance for the treatment of adult growth hormone deficiency with somapacitan, a long-acting growth hormone preparation

Adult growth hormone deficiency (AGHD) is a rare endocrine disorder characterized by an abnormal body composition, metabolic abnormalities associated with increased cardiovascular diseases, bone loss, and impaired quality of life. Daily subcutaneous injections with recombinant growth hormone (GH) can alleviate the abnormalities associated with AGHD. Several long-acting GH (LAGH) preparations are currently in development that aim to reduce treatment burden for patients receiving daily GH injections. Somapacitan (Sogroya®; Novo Nordisk, Denmark) is the first LAGH preparation that has been approved for treatment of AGHD in the United States, Europe, and Japan. The recent approval of somapacitan and anticipated approval of other LAGH molecules presents new questions for physicians planning to treat AGHD with LAGH in the future. Differences in the technologies used to prolong the half-life of recombinant GH are expected to result in variations in pharmacokinetic and pharmacodynamic profiles between preparations. Therefore, it is essential that physicians understand and consider such variations when treating patients with these novel GH replacement therapies. Here, we present a set of treatment recommendations that have been created to guide physicians initiating therapy with somapacitan in patients with AGHD who are eligible for GH replacement. Furthermore, we will review the published data that underlie these recommendations to explain the rationale for the treatment and monitoring advice provided

Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary tumors

Background: Excess mortality due to de novo malignant brain tumors was recently found in a national study of patients with hypopituitarism following treatment of pituitary tumors. Here, we examined a larger multi-national cohort to corroborate and extend this observation. Objective: To investigate the incidence of malignant brain tumors and benign meningiomas in a large cohort of patients treated for pituitary tumors. Patients and Methods: Between 1994-2012, 8917 hypopituitary patients with a pituitary tumor treated with growth hormone (GH) replacement were followed in KIMS (non-interventional Pfizer International Metabolic Database). For 4936 patients, pituitary tumor treatment was surgery/medical therapy, and in 3227 radiotherapy (RT) was used alone or with surgery. For 754 patients, tumor treatment data were missing. Reference incidence rates of malignant brain tumors (ICD10: C70-C72) stratified for age, gender and country (Cancer Incidence in 5 regions, Vol IX, IARC 2007) were used to calculate standardized incidence ratios (SIR). Risk indicators for 2nd central nervous system neoplasia (new malignant brain tumors and benign meningiomas) were analyzed by multiple Poisson regression.Relative risks (RRs) were based on internal comparisons. Results: During 53,881 patient-years at risk, 21 malignant brain tumors (SIR 3.92 95% CI: 2.43-6.00), and 27 benign meningiomas were reported. Fourteen malignant tumors occurred in patients treated with RT, SIR 6.50 (95% CI 3.55-10.91) vs 7 in those without RT. The RR of RT vs no RT for malignant brain tumors was 2.43 (95% CI 1.02-6.29), and for meningiomas was 5.43 (95% CI 2.06 -14.35).On average, the risk for malignant brain tumors increased by 5.9% per year of decreasing age at first radiotherapy (95% CI: 1.2% - 10.3%; p=0.01) and for meningiomas by 5.7% (95% CI: 1.6% - 9.6%; p=0.003). Median times from RT exposure to 2nd tumor diagnosis were 20.3, range 3.1-46.1 yrs, and 22.2, range 8.1-39.3 yrs, for malignant tumors and meningiomas, respectively. Meningiomas were more common in females (18 vs 9, RR=2.26, 95% CI: 1.01-5.05), but there was no difference between genders for malignant brain tumors. The underlying pituitary tumor etiology, number of surgeries, and IGF-I SDS on GH treatment did not influence the risk of 2nd tumors. Conclusion: Radiotherapy is associated with increased risk of developing malignant brain tumors and meningiomas, in particular when given at younger ages. In balancing risks and benefits of RT in the treatment of pituitary tumors, our findings emphasize that special consideration should be given to the age of the patient

Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing’s disease: results from a Phase III study

OBJECTIVE: Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. DESIGN: Phase III study with double-blind randomization of two pasireotide doses. METHODS: Patients (n=162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1.5x upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900μg bid). At month 3, patients with UFC≤2xULN and not exceeding the baseline value continued their randomized dose; all others received 300μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enrolled in the study and with evaluable measurements were assessed in relation to degree of UFC control. RESULTS: Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and LDL-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72.8% of patients. CONCLUSIONS: In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. This article is protected by copyright. All rights reserved