Disclosure: M. Gadelha: Consulting Fee; Self; Crinetics, Ipsen, Novo Nordisk, and
Recordati. Grant Recipient; Self; Crinetics and Recordati. Speaker; Self; Ipsen, Novo
Nordisk, and Recordati. H.S. Randeva: None. M.B. Gordon: Consulting Fee; Self; Crinetics
Pharmaceuticals, HRA Pharma, Novo Nordisk, and Recordati Rare Diseases. Grant Recipient;
Self; Ascendis, Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk,
Opko, Pfizer, and Strongbridge. M. Doknic: Research Investigator; Self; Crinetics
Pharmaceuticals. Speaker; Self; Merck, Novartis, Novo Nordisk, Pfizer, and Sandoz.
E. Mezosi: Research Investigator; Self; Crinetics Pharmaceuticals. M. Toth: Consulting
Fee; Self; Pfizer, Ipsen, Novo Nordisk, and Recordati. Research Investigator; Self;
Crinetics Pharmaceuticals. Other; Self; Pfizer, Ipsen, Novo Nordisk, and Recordati.
C.L. Boguszewski: Advisory Board Member; Self; Novo Nordisk and Recordati. Consulting
Fee; Self; Ipsen, Novo Nordisk, and Recordati. Other; Self; Ipsen, Novo Nordisk, and
Recordati. C. Davidson: Employee; Self; Crinetics Pharmaceuticals. C.T. Ferrara-Cook:
Employee; Self; Crinetics Pharmaceuticals. A. Casagrande: Employee; Self; Crinetics
Pharmaceuticals. A. Krasner: Employee; Self; Crinetics Pharmaceuticals.Paltusotine
is a non-peptide, highly selective SST2 receptor agonist in development as a once-daily,
oral treatment for patients with acromegaly or carcinoid syndrome. ACROBAT Advance
is an ongoing, 6-year, single-arm, open-label extension study of paltusotine in the
treatment of patients with acromegaly. Interim results as the first enrolled patients
approach 4 years of treatment are reported here. Enrolled patients had completed either
the ACROBAT Edge or Evolve phase 2 parent studies. In Edge, at enrollment all patients
were candidates for combination drug therapy: either sub-optimally controlled on an
injected SRL (octreotide or lanreotide) alone or in combination with cabergoline,
or required combination therapy or pasireotide to achieve normal IGF-I levels. In
Evolve, enrolled patients had normal IGF-I levels on injected SRL monotherapy. When
the Advance study was initiated, paltusotine was formulated as a capsule (dose range,
10-40 mg); all patients were switched to the tablet formulation (dose range, 20-60
mg) during the third year of the study. As of this analysis, all patients had at least
2 assessments after switching to tablet formulation. Adjunctive treatment with cabergoline
or pegvisomant was allowed in patients who did not attain normal IGF-I levels on the
maximum dose of paltusotine. Forty-three patients were enrolled in Advance (Edge,
n=32; Evolve, n=11; 88% of eligible patients): at baseline, mean (±SD) age 53.0±11.6
years, 56% female, 86% previous pituitary surgery, and none had prior radiotherapy.
IGF-I control in Edge and Evolve subsets remained stable at parent study baseline
values. For all patients pooled, median (IQR) IGF-I levels were 1.15× ULN (0.84, 1.46;
n=43) at parent study baseline; in Advance, 1.14× ULN (0.89, 1.29; n=40), 1.06× ULN
(0.87, 1.24; n=35), and 1.08× ULN (0.87, 1.57; n=10) at months 12, 24, and 42, respectively.
As expected, patients receiving adjunctive medication during Advance largely derived
from the Edge study. Acromegaly symptoms, as measured using the patient-reported Acromegaly
Symptom Diary (score range, 0-70; higher values indicate greater symptom burden),
were stably controlled: median (IQR) score of 8.6 (3.6, 20.1; n=21) at parent study
baseline; in Advance, 10.5 (5.0, 18.5; n=40), 10.0 (5.0, 25.0; n=34), and 13.5 (6.0,
22.0; n=10) at months 12, 24, and 42, respectively. The most common AEs reported through
month 42 were arthralgia (37.2%), headache (30.2%), and fatigue (23.3%). One serious
drug-related AE (cholelithiasis) was reported. Of the 8 patients who discontinued
the study, 2 were due to AEs (mild or moderate). Glycemic control, as measured by
HbA1c, was stable during paltusotine treatment. In conclusion, long-term results show
that once-daily oral paltusotine treatment was well tolerated, with stable biochemical
and symptom control relative to that observed with injected SRLs. Support: Crinetics
Pharmaceuticals.Presentation: 6/3/2024
