ECE2022 Oral Communications Oral Communications 4: Pituitary and Neuroendocrinology 1 (6 abstracts)
ACROBAT advance: once daily, oral paltusotine treatment maintained long-term igf-1 at levels previously achieved with injectable long-acting somatostatin receptor ligands (LA-SRLs)
Mônica R Gadelha 1 , Harpal Randeva 2 , Murray B Gordon 3 , Emese Mezosi 4 , Mirjana Doknic 5 , Miklós Tóth 6 , Cesar L Boguszewski 7 , Melissa Nichols 8 , Theresa Jochelson 8 , Scott Henley 8 , Meenal Patel 8 , Debbie Koh Mendez 8 , Christine Ferrara-Cook 8 , Alan Krasner 8 , Alessandra Casagrande 8 & R Scott Struthers 8
1Neuroendocrinology Research Center/Endocrinology Division--Medical School and Hospital Universitario Clementino Fraga Filho--Universidade Federal do Rio de Janeiro, Brazil; 2University Hospitals Coventry and Warwickshire NHS Trust, United Kingdom; 3Allegheny Neuroendocrinology Center, Allegheny General Hospital, United States; 4University of Pécs Medical School, 1st Department of Internal Medicine, Hungary; 5Clinical Centre Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Serbia; 6Semmelweis University, Department of Internal Medicine and Oncology, Hungary; 7SEMPR, Endocrine Division, Department of Internal Medicine, Federal University of Parana, Brazil; 8Crinetics Pharmaceuticals, United States
Paltusotine is a once-daily, oral, nonpeptide somatostatin receptor type 2 (SST2) specific agonist, in development for the treatment of acromegaly and neuroendocrine tumors. We report interim results from ACROBAT Advance (NCT04261712), an ongoing, multicenter, open-label, long-term extension study of paltusotine in subjects with acromegaly who previously completed either Phase 2 study ACROBAT Edge (NCT03789656) or Evolve (NCT03792555). ACROBAT Edge enrolled 47 subjects with elevated (n=35) or normal (n=12) IGF-1 taking LA-SRLs either as mono- or combination therapy at baseline. ACROBAT Evolve enrolled 13 subjects with a normal IGF-1 using octreotide LAR or lanreotide depot monotherapy. Both ACROBAT Edge and Evolve involved up to 13-weeks of paltusotine treatment followed by a 1-month drug washout period. In ACROBAT Advance, paltusotine was re-initiated at a dose of 10 mg/day with titration up to 40 mg/day based on IGF-1 and tolerability. For subjects not achieving a normal IGF-1 with 40 mg/day of paltusotine monotherapy, adjunctive treatment was allowed. Of 49 eligible subjects, 41 (84%) [median age 52 (IQR 46-62) years, 56.1% female] were enrolled at the time of the interim analysis, 23 had reached 51 weeks of treatment, and 4 had discontinued from the study. Paltusotine dose was titrated to 40 mg/day in most subjects (73%) by week 51. The frequency of adjunctive cabergoline use during the trial was the same as that prior to the trial (24%). Median IGF-1 was maintained for up to 51 weeks at levels achieved with previous parenteral LA-SRL therapy (Table 1). The most common treatment-emergent adverse events were headache [12 (29.3%)], arthralgia [9 (22%)], and fatigue [6 (14.6%)]. Most adverse events were transient and of mild-to-moderate intensity. There were 3 non-treatment-related SAEs in 2 subjects. There were 4 discontinuations (1 for headache and 3 for study drug unrelated reasons). Median HbA1c levels remained stable [baseline 6.0% (5.7-6.2), 5.9% (5.7-6.1) at week 23, and 5.8% (5.6-6.4) at week 51]. Oral once-daily paltusotine treatment was well tolerated and resulted in maintenance of IGF-1 at levels comparable to prior LA-SRL therapy for up to 51 weeks. This was seen in all subsets of acromegaly patients representing a variety of previous treatment regimens and a range of baseline disease control.
| Previous LA-SRL therapy* | ACROBAT Advance Week 31* | ACROBAT Advance Week 51* | |
| ACROBAT Edge subjects | 1.31&unixF0B4;ULN (1.02,1.48) (n=30) | 1.30&unixF0B4;ULN (0.91,1.54) (n=21) | 1.15&unixF0B4;ULN (1.01,1.49) (n=17) |
| ACROBAT Evolve subjects | 0.83&unixF0B4;ULN (0.64,0.94) (n=11) | 0.84 (0.75,0.96) (n=10) | 0.89 (0.83,1.06) (n=6) |
| *Median IGF-1&unixF0B4;Upper Limit Normal (IQR) | |||
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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