Oral Paltusotine Maintains Acromegaly Disease Control for Up to 4 Years in Patients Previously on Injected SRLs
Background
Acromegaly is a chronic endocrine disorder caused by excess growth hormone (GH) and insulin-like growth factor-I (IGF-I), primarily due to a pituitary adenoma. Current standard-of-care often involves surgery, radiotherapy, and long-acting injectable somatostatin receptor ligands (SRLs) like octreotide or lanreotide. These injections can be burdensome, leading to compliance issues and reduced quality of life. There's a significant need for effective, convenient oral alternatives to improve patient adherence and management of acromegaly. Paltusotine, a non-peptide selective somatostatin 2 receptor agonist, aims to address this gap.
Study Design
The ACROBAT Advance study is an ongoing open-label extension (OLE) evaluating long-term paltusotine treatment. Patients (n=43) who completed prior Phase 2 studies (ACROBAT Edge/Evolve) were enrolled. These patients had either elevated IGF-I on injected SRLs or controlled IGF-I on SRL monotherapy. Patients received once-daily oral paltusotine, initially up to 40 mg, then up to 60 mg from year 3 with a new tablet formulation. Adjunctive cabergoline or pegvisomant was permitted. Primary endpoints included safety, IGF-I levels, growth hormone levels, acromegaly symptoms, and pituitary tumor size stability over 4 years.
Results
Paltusotine demonstrated long-term disease control in acromegaly patients for up to 4 years. Median IGF-I levels were 1.15xULN (0.84, 1.46) at parent study baseline (n=43), 1.17xULN (0.98, 1.54) at Advance week 3 (n=43), and significantly improved to 1.01xULN (0.83, 1.13) at Advance week 207 (n=20). Growth hormone levels, acromegaly symptoms, and pituitary tumor size remained stable throughout the study period. As of this analysis, 8 (18.6%) patients had discontinued from the study. Only 2 (4.7%) discontinuations were due to adverse events, indicating good long-term tolerability.
Paltusotine was well tolerated, with no unexpected safety findings observed over the 4-year period.
Key Findings
- Median
IGF-Ilevels decreased from 1.15xULN at baseline to 1.01xULN at week 207 (4 years). - Growth hormone levels, acromegaly symptoms, and pituitary tumor size remained stable over 4 years.
- Paltusotine was well tolerated with no unexpected safety findings observed.
- Only 4.7% of patients discontinued due to adverse events over the 4-year period.
Why It Matters
This study provides crucial long-term safety and efficacy data for paltusotine, supporting its use as a convenient oral alternative for acromegaly patients. Switching from burdensome injectable somatostatin receptor ligands (SRLs) to a once-daily oral regimen could significantly improve patient adherence and quality of life. For clinicians, this offers a new, well-tolerated option for maintaining disease control. While this is an open-label extension, the sustained control over 4 years suggests a viable long-term protocol, potentially reducing the need for frequent clinic visits associated with injectables.
paltusotine
acromegaly
somatostatin-receptor-agonist
long-term
oral
clinical-trial