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Abstract Disclosure: M. Fleseriu: Consulting Fee; Self; Novo Nordisk, Amryt Pharma Holdings Ltd, Ascend Therapeutics (A Besins Healthcare company). Speaker; Self; Xeris Pharmaceuticals, Inc. , RECORDATIRAREDISEASESINC. , Ipsen Pharma SAS. S. L. Samson: Advisory Board Member; Self; Amryt. Research Investigator; Self; Amryt. N. Biermasz: Advisory Board Member; Self; Recordati, Pfizer Global R Self; Macro Registry Grant, Amryt. C. J. Strasburger: Advisory Board Member; Self; Sandoz, Ipsen, Recordati. Consulting Fee; Self; Ascendis, Amryt, Novo Nordisk, Merck, Sandoz, Recordati. Speaker; Self; Ipsen, Novo Nordisk, HRA-Pharma. S. Fuchs Orenbach: Employee; Self; Chiesi Global Rare Diseases. J. A. Crompton: Employee; Self; Chiesi Global Rare Diseases. S. Melmed: Advisory Board Member; Self; Ionis, Crinetics. Consulting Fee; Self; Ipsen. Grant Recipient; Self; Pfizer. Background: Treatment with oral octreotide capsules (OOC) was evaluated in three phase 3 trials (CH-ACM-01, OPTIMAL, MPOWERED) in patients with acromegaly who previously tolerated and responded to the injectable somatostatin receptor ligands (iSRLs) octreotide and lanreotide. Results demonstrated efficacy and safety despite differences in trial design. Pooling data from all three trials can provide further insight into the biochemical response, symptom improvement, and safety profile of OOC. Objective: Analyze the biochemical changes, symptom control, and safety of OOC through a pooled analysis of phase 3 clinical trial datasets. Methods: Patients included were aged ≥18 years with acromegaly and responded biochemically to iSRL therapy before the initiation of OOC (defined as IGF-I 1. 3 × ULN and mean integrated GH 2. 5 ng/mL for CH-ACM-01 and MPOWERED, and IGF-I ≤1. 0 × ULN for OPTIMAL). Data analyzed were from the following periods: baseline until the end of the double-blind placebo-controlled phase of OPTIMAL (36 weeks) ; the run-in phase of MPOWERED (26 weeks) ; end of dose escalation (2-5 months; efficacy data) and end of fixed dose phase (up to 7 months, safety data) for CH-ACM-01. Effect of prior iSRL dose was analyzed using a random effects meta-analysis. Symptom severity was scored using the Acromegaly Index of Severity (AIS) tool. Results: Efficacy, symptom, and safety data were available for 318, 194, and 329 patients, respectively. The overall response rate was 65% with no effect of prior iSRL dose (p0. 05). Mean (SD) IGF-I change from baseline was +0. 17 (0. 32; n=214), +0. 19 (0. 39; n=81), and +0. 22 (0. 57; n=23) for patients with baseline IGF-I levels ≤1 × ULN, 1 to 1. 3 × ULN, and ≥1. 3 × ULN. Twenty percent (16/81) and 35% (8/23) of patients with baseline IGF-I of 1 to 1. 3 x ULN and ≥1. 3 x ULN shifted to an improved category of response. There was a median decrease of one symptom per patient (p0. 05) and a mean decrease of 0. 8 in AIS (p0. 05). The proportion of OOC responders reporting ≤1, 2, or 3 moderate/severe acromegaly symptoms at baseline and month 6 decreased from 56% to 39%, 32% to 20%, and 20% to 12%. At month 6, improvement was seen for all individual symptoms (joint pain, swelling, sweating, fatigue, headache) of moderate/severe grade and was significant for joint pain (36% to 22%) and swelling (15% to 10%) (p0. 02). Most adverse events (AEs) were gastrointestinal (GI) in nature (54%, n=179/329) with a median onset and duration of 15 and 12 days for first reported GI events. Conclusion: Pooled analysis confirms overall maintenance of biochemical control in patients previously responding to iSRL therapy, with decreased symptom burden in OOC responders. OOC was generally well tolerated with no new safety signals. GI-related AEs were largely transient. These results support OOC as a therapeutic option for treating acromegaly. Presentation: 6/3/2024
Fleseriu et al. (Tue,) studied this question.