Paltusotine is a once-daily, oral, non-peptide small-molecule somatostatin receptor
type 2 (SST2) agonist in clinical development for treatment of acromegaly.To evaluate
change in IGF-I levels in patients switched from octreotide LAR or lanreotide depot
monotherapy to paltusotine.Phase 2, open-label, prospective, multicenter, multinational,
non-randomized, single-arm exploratory study in which dosage up-titrations were performed
in a double-blinded manner.26 global sites.Patients with acromegaly switched to paltusotine
from injected SRL-based therapy.Patients received 13-week treatment with once-daily
oral paltusotine (10-40 mg/day).Primary endpoint was change from baseline to week
13 in IGF-I for patients who switched from long-acting octreotide or lanreotide monotherapy
to paltusotine (Group 1). All patients underwent a 4-week paltusotine washout at end
of treatment period (weeks 13-17). IGF-I, GH, patient reported outcome, and safety
data were collected.Forty-seven patients enrolled. In Group 1 (n = 25), IGF-I and
GH showed no significant change between SRL baseline and end of paltusotine treatment
at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN], P = 0.6285;
GH = -0.05 ng/mL, P = 0.6285). IGF-I and GH rose significantly in the 4 weeks after
withdrawing paltusotine (median change in IGF-I = 0.55×ULN, P < 0.0001 [median increase
39%]; GH = 0.72 ng/mL, P < 0.0001 [109.1% increase]). No patients discontinued due
to adverse events; no treatment-related serious adverse events were reported.These
results suggest once daily, oral paltusotine is effective in maintaining IGF-I values
in patients with acromegaly who switched from injected SRLs. Paltusotine was well
tolerated with a safety profile consistent with other SRLs.
