In patients suboptimally controlled on LAR, PM and P-LAR were equally well tolerated and effective in normalizing IGF-I, and overall clinical improvement was observed with both regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable options for the treatment of LAR-resistant acromegaly.

Objective: Changes observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG-GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects. Design and methods: This was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG-GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A-D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG-GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG-GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG-GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy. Results: A total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG-GH dose or IGF1 levels, either basal or under treatment. Conclusion: The unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.

PurposeThis phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH).Methods61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 μg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 μg (300 μg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability.ResultsRalinepag significantly decreased PVR by 163.9 dyn·s·cm−5 compared to an increase of 0.7 dyn·s·cm−5 with placebo (p=0.02); the least-squares mean change from baseline PVR was −29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients.SummaryRalinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.

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