Fleseriu, Maria

Abstract Context Biochemical test results are central to clinical decision-making for the diagnosis and management of Cushing syndrome (CS). With emerging research and increasing availability of different tests, updated consensus on the utility of these biomarkers is warranted. Objective To establish an updated consensus on the role of biomarkers in the diagnosis and monitoring of adrenocorticotropic hormone-dependent CS, address novel therapeutic approaches, and identify areas for future research. Design A modified 2-round Delphi panel was conducted. Consensus was defined as ≥70% agreement/disagreement for Likert-scale statements or ≥70% selection of the same option for single-choice questions. Setting Participants represented a range of international expertise. Participants Forty-one participants took part in the Delphi panel, with no attrition between rounds (one nonclinician was not required to complete the second round). An 8-member Steering Committee guided statement development. Results Of statements designed to reach consensus, 45% (14/31) and 44% (11/25) statements reached consensus in Rounds 1 and 2, respectively. Notably, most panelists reported the use of late-night salivary cortisol for diagnosis of mild CS and for monitoring following pituitary surgery or medical or radiation therapy. Most panelists responded that block-and-replace therapies can be considered in patients with cyclical or severe CS, and consensus was reached that restoration of circadian rhythm is a treatment goal for patients with CS. Conclusion Areas of alignment among experts on the diagnosis and monitoring of CS are presented. The findings from this study are intended to support clinicians in their clinical decision-making and highlight priority areas for future research.

Abstract Context Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. Objective This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. Methods The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. Results At week 38, lonapegsomatropin significantly reduced trunk percent fat (−1.68% vs +0.37%; least squares [LS] mean difference −2.04%; P < .001), increased total body lean mass (+1.60 kg vs −0.11 kg; LS mean difference 1.70 kg; P < .0001), and reduced trunk fat mass (−0.48 kg vs +0.22 kg; LS mean difference −0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. Conclusion The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.

Abstract Disclosure: M. Fleseriu: None. C.P. Badiu: None. I. Bancos: None. E.B. Geer: None. M. Orbetzova: None. J.M. Silverstein: None. I. Uzunova: None. K.C. Yuen: None. T.K. Marmon: None. D.A. Katz: None. F.S. Czerwiec: None. Introduction: 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) regulates exposures of intracellular receptors to active glucocorticoids. HSD-1 deficiency suppresses a Cushing syndrome (CS) phenotype despite presence of hypercortisolism.1-3 Treatment with clofutriben (C), a potent and specific inhibitor of HSD-1, might improve CS comorbidities by decreasing intracellular cortisol. Methods: Seventeen adults with CS (16 pituitary, 1 ectopic), and type 2 diabetes (T2D), impaired glucose tolerance (IGT), hypertension (HTN), hyperlipidemia, or osteopenia were randomized to a total of 12 weeks of oral C 6mg/d and 12 weeks of matching placebo (P) in 2 blinded sequences (PCCP, CCPP; “P” or “C” representing 6-week periods). Patients were offered open-label C treatment on completion. Primary endpoint was urinary ratio of cortisol and cortisone metabolites at Week 6 (hepatocellular HSD-1 activity biomarker). Key exploratory endpoints (and applicable population) at Week 6 were OGTT-AUCglucose decrease 25% (IGT/T2D), HbA1c decrease ≥ 0.5% (T2D), systolic blood pressure decrease ≥ 5mmHg or decreased treatment (HTN), and normalization of urinary free cortisol (baseline >1.5xULN). Results: Mean baseline HSD-1 ratio was 1.95 +/- 0.171. At Week 6, mean ratio was 0.21 +/- 0.091 with C and 2.01 +/- 0.263 with P. More patients responded at Week 6 to C on OGTT-AUCglucose (4/8 v 0/5), HbA1c (4/5 v 0/4), systolic blood pressure (5/7 v 2/4), and urinary free cortisol (3/8 v 0/6). Concomitant medications for T2D were reduced in 4 C-treated but increased in 2 P-treated patients. For HTN there were also 4 reductions for C-treated and 1 increase for P-treated patients. One patient succumbed to ectopic Cushing’s due to cervical carcinoma after discontinuing the trial. Four patients discontinued for reasons other than an adverse event (AE). One serious AE of vomiting (possible glucocorticoid withdrawal syndrome per investigator) led to temporary drug interruption. Common AEs (≥ 3 patients) included Arthralgia, Fatigue, Headache, and Nausea, but only Headache was more common in C during the P-controlled period. There was no evidence of clinical or biochemical (defined by low morning plasma cortisol) adrenal insufficiency. All 13 patients who completed elected to enter the open-label extension (current treatment duration 3-15 months). Conclusions: Clofutriben decreased hepatic HSD-1 activity adequately to confer clinical benefit while maintaining safety and overall tolerability. These limited data support clofutriben’s potential for clinical improvement without adrenal insufficiency. References: 1Tomlinson JW 2002; 2Arai H 2008; 3Weber RJ 2024 Presentation: Sunday, July 13, 2025

Abstract Objective Increased frequency of neuroimaging has led to enhanced identification of small nonfunctioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs. Design A systematic review and individual participant data (IPD) meta-analysis. Methods We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share IPD. Cohort studies including patients with conservatively treated micro-NFPAs with at least 1 follow-up magnetic resonance imaging were considered eligible. Fourteen studies met inclusion criteria. Six authors provided IPD (N = 647). Data were reanalyzed for verification. In cases of discrepancies the original authors were contacted for authentication. Results Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the 2-step approach. Overall probability of surgery was 0.2/100 PYs (95% CI: 0.0-0.4; I2 = 28%). Probability of surgery due to visual impairment was 0.1/100 PYs (95% CI: 0.0-0.2; I2 = 0%). Both were independent of baseline tumor size (≥6 or <6 mm), sex, or age (P values >.40). Risk of developing a new endocrinopathy was 1.0/100 PYs (95% CI: 0.4-1.6; I2 = 0%). Data for classical meta-analysis were available for 7 studies (N = 1089) and supported the IPD results. Conclusions These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.

Abstract Although most cases of endogenous Cushing syndrome are caused by a pituitary adenoma (Cushing disease), approximately one-third of patients present with ectopic or adrenal causes. Surgery is the first-line treatment for most patients with Cushing syndrome; however, medical therapy is an important management option for those who are not eligible for, refuse, or do not respond to surgery. Clinical experience demonstrating that osilodrostat, an oral 11β-hydroxylase inhibitor, is effective and well tolerated comes predominantly from phase III trials in patients with Cushing disease. Nonetheless, reports of its use in patients with ectopic or adrenal Cushing syndrome are increasing. These data highlight the importance of selecting the most appropriate starting dose and titration frequency while monitoring for adverse events, including those related to hypocortisolism and prolongation of the QT interval, to optimize treatment outcomes. Here we use illustrative case studies to discuss practical considerations for the management of patients with ectopic or adrenal Cushing syndrome and review published data on the use of osilodrostat in these patients. The case studies show that to achieve the goal of reducing cortisol levels in all etiologies of Cushing syndrome, management should be individualized according to each patient’s disease severity, comorbidities, performance status, and response to treatment. This approach to osilodrostat treatment maximizes the benefits of effective cortisol control, leads to improvements in comorbid conditions, and may ameliorate quality of life for patients across all types and severities of Cushing syndrome.

Abstract Disclosure: M. Fleseriu: Consulting Fee; Self; Novo Nordisk, Amryt Pharma Holdings Ltd, Ascend Therapeutics (A Besins Healthcare company). Speaker; Self; Xeris Pharmaceuticals, Inc., RECORDATI_RARE_DISEASES_INC., 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&D. Grant Recipient; 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 (p>0.05). 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 (p<0.05) and a mean decrease of 0.8 in AIS (p<0.05). 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%) (p<0.02). 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

Abstract Disclosure: B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Novartis Pharmaceuticals, Sparrow, Strongbridge Biopharma. Grant Recipient; Self; Strongbridge Biopharma. A. Gilis-Januszewska: Speaker; Self; Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Recordati, Teva Pharmaceutical Industries Ltd.. M. Doknic: None. A.M. Pico: None. M. Fleseriu: Consulting Fee; Self; Ascendis, GlaxoSmithKline, Johnson &Johnson, Karyopharm, Novo Nordisk, Pfizer, Inc., Pharmacosmos. Research Investigator; Self; Ascendis. G. Raverot: None. A.M. Isidori: None. Y. Takahashi: None. J.M. Garcia: None. J.M. Silverstein: None. I. Bancos: None. E. Huang: Employee; Self; Ascendis Pharma, Inc. J. Kang: Employee; Self; Ascendis Pharma, Inc. A.S. Komirenko: Employee; Self; Ascendis Pharma, Inc. L. Domrzalski: Employee; Self; Ascendis Pharma, Inc. A. Shu: Employee; Self; Ascendis Pharma, Inc. K. Yuen: Advisory Board Member; Self; Amryt, Ascendis, Corcept, Crinetics, Novo Nordisk, Recordati, Strongbridge, Xeris. Grant Recipient; Self; Amryt, Ascendis, Corcept, Crinetics. Speaker; Self; Corcept, Novo Nordisk, Recordati. Background: Adult GHD (aGHD) is characterized by metabolic abnormalities due to insufficient growth hormone (GH) production. Lonapegsomatropin was designed to provide sustained release of unmodified somatropin, with the identical amino acid sequence as endogenous GH, and once-weekly injection reduces the burden of daily GH replacement therapy. MethodsForesiGHt was a randomized, parallel-3-arm, placebo(PL)-controlled (double-blind) and active-controlled (open-label) trial designed to establish the efficacy and safety of lonapegsomatropin in aGHD. It evaluated 259 adults with GHD across 21 countries who were GH treatment-naïve or not treated with GH in the prior year, randomized 1:1:1 to receive lonapegsomatropin, once-weekly PL, or daily somatropin (dGH). Fixed dosing was based on age and oral estrogen intake, and designed to be comparable across lonapegsomatropin and dGH arms. Following a 12-week (w) titration period to target maintenance dose, fixed doses were administered for 26w. ResultsBaseline (BL) characteristics were similar between arms. Lonapegsomatropin demonstrated superiority on the primary efficacy endpoint of change from BL in trunk percent fat at Week 38 vs PL (lonapegsomatropin -1.7% vs PL 0.4%, LS mean difference -2.0%, p < 0.0001) and on the key secondary efficacy endpoints of change from BL in total body lean mass (lonapegsomatropin 1.6 kg vs PL -0.1 kg, LS mean difference 1.7 kg, p < 0.0001) and change from BL in trunk fat mass (lonapegsomatropin -0.5 kg vs PL 0.2 kg, LS mean difference -0.7 kg, p = 0.0053). Mean total exposure and maintenance doses were similar for lonapegsomatropin and dGH arms, with larger changes from BL in average IGF-I SDS mean at Week 38 in the lonapegsomatropin arm (1.4) vs dGH arm (0.5). To assess outcomes at comparable weekly IGF-I exposure, a post-hoc analysis was performed in a subset of participants with average IGF-I SDS ≤1.75 SDS at Week 38. Mean IGF-I SDS for these subsets were similar (lonapegsomatropin -0.1, dGH -0.5), and comparable effects in fat and lean tissue compartments were demonstrated (change from BL in trunk percent fat mean -2.4% and -2.6% respectively; change from BL in total body lean mass mean 1.7 kg and 1.4 kg respectively). In the safety population, the incidence of severe AEs was low (lonapegsomatropin, 3.4%; placebo, 1.2%; dGH, 2.3%) and the incidence of treatment-related AEs was similar (lonapegsomatropin 24.7%, dGH 22.1%). Injection site reaction incidence was low and similar for lonapegsomatropin (4.5%), dGH (5.8%) and placebo (4.8%), and A1c levels remained stable in all treatment arms. ConclusionsThe results of the foresiGHt trial indicate that lonapegsomatropin is a safe, efficacious, and tolerable replacement for endogenous GH. Once-weekly dosing may be impactful for adults with GHD who typically manage multiple other medical therapies. Presentation: 6/3/2024

Abstract Disclosure: I. Bancos: Advisory Board Member; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Consulting Fee; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Grant Recipient; Self; Recordati, HRA Pharmaceuticals. Other; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. E.B. Geer: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Xeris Pharmaceuticals (Strongbridge), Corcept, Recordati Rare Diseases, Sparrow. F. Castinetti: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; HRA Pharmaceuticals, Recordati. R. Feelders: Advisory Board Member; Self; Recordati. Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Fleseriu: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). R. Pivonello: Consulting Fee; Self; Corcept Therapeutics, Recordati, Crinetics Pharmaceuticals, H Lundbeck. Grant Recipient; Self; Recordati, Corcept Therapeutics, Xeris Pharmaceuticals (Strongbridge), Neurocrine Biosciences. M. Reincke: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Grant Recipient; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Speaker; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. A. Tabarin: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases. J. Le Mouhaër: Employee; Self; Recordati. J. Stermenska: Employee; Self; Recordati. M. Maldonado: Employee; Self; Recordati. B.M. Biller: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provides control of cortisol production and improves outcomes in patients (pts), as shown by the clinical development program of Cushing’s disease (CD; Fleseriu M et al. Lancet Diabetes Endocrinol 2021;9:847-75) leading to EMA approval for Cushing’s syndrome (CS) and FDA approval for CD. The prospective LINC 6 study (NCT05382156) evaluates long-term safety and efficacy of osilodrostat in routine clinical practice over a 3-­year follow-up of CS pts. Here, we report 1-year interim data. Methods: Pts aged ≥18 years with endogenous CS are being enrolled in countries where osilodrostat is approved and available (including USA and Europe), irrespective of prior osilodrostat use. Treatment decisions and follow-up are at investigator discretion. The primary endpoint is incidence of osilodrostat-related adverse events (AEs) and serious AEs, focusing on AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement. Secondary endpoints include change in mean urinary free cortisol (mUFC), serum cortisol and late-night salivary cortisol (LNSC). Evaluation of biochemical parameters is recommended at baseline, months 1 and 3, and every 3 months thereafter, as available. AEs are recorded at baseline and each visit. Analyses are descriptive. We report change for pts with assessments at baseline and every 3 months. Results: Of 106 pts enrolled at the 1-year interim analysis, 94 were included in the safety population: CD, n=78; non-CD CS, n=16 (adrenal adenoma, n=3; adrenal hyperplasia, n=3; ectopic, n=9; other, n=1). Mean (SD) age was 53.2 years (12.7); 70.2% (n=66) were female. Median (min-max) osilodrostat exposure and dose were 5.5 months (0.1-13.9) and 5.0 mg/day (1.0-60.0). 29 pts reported 109 AEs; 12 pts reported 44 AEs that were considered treatment related. Overall, the most common (≥5%) AEs were asthenia and vomiting (both n=6/109; 5.5%); treatment-related AEs with highest frequency were vomiting and dizziness (both n=4/44; 9.1%). 7 AEs led to discontinuation in 4 pts; 5 AEs were considered osilodrostat related (nausea and vomiting in 1 pt; worsening hypertension, uncontrolled blood pressure and dizziness in another) and 2 were not (pituitary tumor surgery and right adrenalectomy). AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement occurred in 7 (7.4%), 4 (4.3%), 2 (2.1%) and 0 pts, respectively. At month 3, mUFC, serum cortisol and LNSC were normalized in 71.4% (n=10/14), 69.2% (n=18/26) and 50.0% (n=7/14) of pts. Conclusions: Results from this real-world clinical setting show that osilodrostat is generally well tolerated and provides early improvements in mUFC and LNSC in pts with endogenous CS, building on evidence from the previous randomized, controlled trials LINC 3 and LINC 4. Presentation: 6/3/2024

Abstract Objective The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response. Design The study design is an OLE of a double-blind placebo-controlled (DPC) trial. Methods Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/day. The OLE is ongoing; week 48 results are reported. Results Forty patients were enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e. insulin-like growth factor I (IGF1) ≤ 1.0 × upper limit of normal (ULN)) was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF1 levels were maintained between the end of the DPC period (0.91 × ULN; 95% CI: 0.784, 1.045) and week 48 of the OLE (0.90 × ULN; 95% CI: 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure.