FDA Approves Paltusotine as First Once-Daily, Oral Therapy for Acromegaly in Adults

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The US FDA has approved paltusotine (Palsonify™, Crinetics Pharmaceuticals), the first once-daily oral treatment for acromegaly in adults, according to an announcement from Crinetics Pharmaceuticals. Approval covers patients who have had an inadequate response to surgery or for whom surgery is not an option.¹

Paltusotine is a selectively targeted somatostatin receptor type 2 (SST2) agonist developed as a convenient oral alternative to injectable therapies traditionally used in acromegaly management. The approval was supported by results from the phase 3 PATHFNDR-1 and PATHFNDR-2 trials, which demonstrated consistent biochemical control, symptom reduction, and a favorable safety profile. No serious adverse events were reported in the randomized controlled portions of either trial.¹

The PATHFNDR program included 2 double-blind, placebo-controlled studies. PATHFNDR-1 enrolled 58 adults with acromegaly who maintained insulin-like growth factor 1 (IGF-1) levels ≤1.0 times the upper limit of normal (ULN) on stable injectable therapy with octreotide or lanreotide. Participants were randomized to receive oral paltusotine or placebo for 36 weeks. PATHFNDR-2 enrolled 112 adults with acromegaly who were either treatment-naïve or not receiving pharmacotherapy and had elevated IGF-1 at baseline. The primary endpoint in both studies was the proportion of participants achieving IGF-1 ≤1.0 x ULN compared with placebo.¹

In September 2023, Crinetics reported that PATHFNDR-1 met its primary endpoint with statistical significance (P < .0001). Eighty-three percent of participants treated with paltusotine maintained IGF-1 ≤1.0 x ULN compared with 4% of placebo-treated participants. All secondary endpoints, including measures of symptom improvement, also met statistical significance.^1,2

Across both studies, participants reported reductions in headache, joint pain, sweating, fatigue, swelling, and neuropathic symptoms, as measured by the FDA-aligned Acromegaly Symptom Diary. Long-term findings from the open-label extension phases presented at ENDO 2025 showed durable IGF-1 control, sustained symptom improvements, and a consistent safety profile, with 91% of PATHFNDR-1 participants and 97% of PATHFNDR-2 completers continuing into the extension.¹

“The PATHFNDR clinical development program set a new standard for acromegaly treatment by demonstrating the ability of [paltusotine] to drive both biochemical and symptom control, regardless of the degree of underlying disease severity,” Shlomo Melmed, MD, executive vice president of medicine and health sciences at Cedars-Sinai, said in a September 25, 2025, press release. “The approval of [paltusotine] is a significant advancement for our patients, as there is an unmet need for an easy-to-administer and safe therapeutic option with a rapid action and durable response that can consistently manage acromegaly.”¹

Paltusotine is expected to be available in the US in early October 2025. Crinetics has also introduced CrinetiCARE, a support program offering benefit verification, financial assistance, education, and nurse educator support to assist patients beginning therapy.¹

The company noted that a Marketing Authorization Application for paltusotine is under review in the European Union, with an opinion expected in the first half of 2026. In Japan, Crinetics is partnering with Sanwa Kagaku Kenkyuso for development and commercialization. Paltusotine is also being investigated in the pivotal phase 3 CAREFNDR trial for carcinoid syndrome, with global enrollment underway in 2025.¹

References:

1. Crinetics Pharmaceuticals. Crinetics announces FDA approval of Palsonify (paltusotine) for the treatment of acromegaly in adults. News release. September 25, 2025. Accessed September 26, 2025. https://crinetics.com/crinetics-announces-fda-approval-of-palsonify-paltusotine-for-the-treatment-of-acromegaly-in-adults/
2. Crinetics Pharmaceuticals. Crinetics’ Once-Daily Oral Paltusotine Achieved the Primary and All Secondary Endpoints in the Phase 3 PATHFNDR-1 Study Evaluating Treatment of Patients with Acromegaly. September 10, 2023. Accessed September 26, 2025. https://crinetics.com/crinetics-paltusotine-achieved-primary-and-secondary-endpoints-in-phase-3-pathfndr-1-acromegaly-study/