Real-World Data Reinforces Paltusotine’s IGF-1 Reductions in Acromegaly, With Leena Shahla, MD

Paltusotine reduces insulin-like growth factor 1 (IGF-1) levels in adult patients with acromegaly while lessening treatment burden and without new safety signals, based on a recent study.1

Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, by Leena Shahla, MD, medical director at the Duke Pituitary Center and associate professor of medicine and neurosurgery at Duke University, these data highlight the safety and efficacy of paltusotine, as well as its capacity for reducing injection burden in adult patients.

“These injections are not easy – they’re painful, they may cause bruises, tenderness, patients worry about where and how to take them,” Shahla told HCPLive in an exclusive interview. “They may need an office visit every month to take the injection, or they may need home visits by a nurse to help with the injection, which will affect their schedule. Having another option like paltusotine, an oral medication, is excellent for patients.”

Paltusotine first received US Food and Drug Administration (FDA) approval in September of 2025, under the name PALSONIFY. The decision was based on a pair of pivotal phase 3 trials, PATHFNDR-1 and PATHFNDR-2, which displayed paltusotine’s safety and efficacy in medically untreated adults with acromegaly. Paltusotine exhibited rapid onset, sustained efficacy, and reliable biochemical control throughout both trials.2

The present study included adult patients with a confirmed diagnosis of acromegaly who had been prescribed paltusotine at 1 of 3 US-based pituitary centers and who had ≥1 IGF-1 level available after drug initiation. Medical records were scanned for demographic and clinical characteristics, treatment history, IGF-1 levels, acromegaly symptoms, and paltusotine dosing.1

A total of 6 patients were enrolled in the study. Patient ages ranged from 25 to 58 years, and all patients had undergone a prior pituitary adenoma resection. 3 of these patients had no history of acromegaly medications, while the others had received and eventually discontinued lanreotide, ocreotide, carbergoline, or any combination of these drugs. Each patient received a dose of paltusotine between 20 and 40 mg per day.1

At baseline, IGF-1 levels ranged from 304 to 674 ng/mL. After 3-4 weeks, IGF-1 levels dropped to around 164-281 ng/mL in all but 1 patient. The upper limit of normalized IGF-1 ranged from 328 to 347 ng/mL across all 3 study centers.1

Additionally, Shahla and colleagues analyzed individual patient outcomes before and after treatment. After 3-4 weeks of treatment, patient 1 saw more regular menses, resolved joint pain, and increased energy, among other outcomes. Patient 2 saw improved sleep and sleep apnea, improved blood pressure, smoother facial features, and increased energy. Patient 3 saw a reduction in speech slurring and resolution of headaches, while patient 4 saw improved sleep and decreased joint pain and sweating. Patient 5 saw their hand joint pains resolved and their headaches improved, while Patient 6 saw improved blood glucose levels after treatment.1

Shalha and colleagues determined that this study proved paltusotine’s efficacy and reinforced its safety profile. However, the team also encourages additional real-world studies, including larger sample sizes.1

“Rather than worrying or going through the struggles with the injections and the pain and the hassle, taking oral medication is easier,” Shahla said. “It’s more convenient, and it will maintain their biochemical and symptom control. If a patient would rather avoid an injection, they now have the option to.”

Editors’ Note: Shahla reports disclosures with Camurus, Chiesi Farmaceutici, Crinetics Pharmaceuticals, and Recordati Rare Diseases.

References

1. Shahla L, Galbiati F, Blevins L, Yuen K. Once-Daily Oral Paltusotine in the Treatment of Adults With Acromegaly: Initial Real-World Experience. Presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.

2. Crinetics Pharmaceuticals. Crinetics Announces FDA Approval of PALSONIFY (paltusotine) for the Treatment of Acromegaly in Adults. September 25, 2025. Accessed April 30, 2026. https://crinetics.com/press-releases/crinetics-announces-fda-approval-of-palsonify-paltusotine-for-the-treatment-of-acromegaly-in-adults/