Crinetics paltusotine shows durable acromegaly control at two years

Crinetics Pharmaceuticals presented long-term data from its PATHFNDR-1 and PATHFNDR-2 open-label extension (OLE) trials at ENDO 2026 on Sunday, showing that its approved oral therapy PALSONIFY (paltusotine) sustained biochemical and symptomatic control of acromegaly for up to two years.

The pooled OLE population covered 167 patients. In PATHFNDR-1, which enrolled adults already biochemically controlled on monthly injectable somatostatin receptor ligands (SRLs), mean IGF-1 levels were 0.91x the upper limit of normal (ULN) at OLE entry and remained essentially flat at 0.82x ULN at 48 weeks and 0.81x ULN at 96 weeks. In PATHFNDR-2, which enrolled medically untreated patients with a higher baseline IGF-1 of 1.64x ULN, levels fell to 1.06x ULN at 48 weeks and 0.96x ULN at 72 weeks. Acromegaly symptom scores, measured via the Acromegaly Symptom Diary, were stable across both studies at all assessed timepoints, and pituitary tumour volumes were stable or reduced for all evaluable patients.

Safety and combination data

No new safety signals emerged in the pooled analysis. The most frequently reported adverse events were diarrhoea (15.6%), arthralgia (11.4%), headache (11.4%), and urinary tract infection (10.2%). Only four patients (2.4%) discontinued an OLE due to adverse events. Separately, Crinetics presented up-to-four-year data from its ACROBAT Advance phase 2 extension study, showing that adding oral cabergoline to paltusotine improved biochemical control in patients who had not yet achieved IGF-1 normalisation on monotherapy, with the combination reported as well tolerated.

Alan Krasner, Chief Endocrinologist at Crinetics, said the data indicate the therapy "is well tolerated and maintains control of all three aspects of disease control with long-term follow-up," adding that since its launch late last year the drug "is already making a meaningful difference in the lives of many people with acromegaly."

Market context

Paltusotine received US FDA approval and EMA authorisation as the first once-daily oral treatment for acromegaly in adults whose disease was inadequately controlled by surgery. The previous standard of care relied on monthly subcutaneous or intramuscular injections of peptide SRLs such as octreotide and lanreotide, a significant burden for patients managing a chronic condition. The shift toward oral small-molecule alternatives in endocrine diseases mirrors broader trends in other chronic indications where injectable biologics have historically dominated.

Acromegaly is a rare condition, estimated to affect roughly 60 patients per million people, and the commercial opportunity is relatively concentrated. Crinetics is also advancing paltusotine into a phase 3 carcinoid syndrome programme (CAREFNDR), which would materially expand the addressable market if successful. The company's pipeline additionally includes atumelnant for congenital adrenal hyperplasia and Cushing's syndrome, positioning Crinetics as a specialist in GPCR-targeted endocrine medicine. Two-year durability data of the type presented at ENDO 2026 are likely to support formulary discussions and physician confidence in switching patients from established injectables, which remains a key commercial hurdle for any oral entrant in a field where prescribers have decades of experience with existing agents.