FDA approves a once-daily pill for acromegaly, replacing monthly injections

The FDA approved Palsonify (paltusotine) tablets on 25 September, for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option [s1]. It is an oral, once-daily alternative to a class of drugs that has been delivered by injection for three decades.

The application was received on 25 September 2024 and approved exactly a year later [s1]. FDA did not refer it to an advisory committee, stating in the approval letter that outside expertise was not necessary and that there were no controversial issues that would benefit from advisory committee discussion [s1].

What changes for patients

Acromegaly is driven by excess growth hormone, and disease control is judged biochemically against insulin-like growth factor 1 (IGF-I) and growth hormone levels [s2]. The indication FDA granted describes the treatment sequence: Palsonify is for adults who had an inadequate response to surgery and/or for whom surgery is not an option [s1]. When surgery does not achieve control, the established medical therapy has been an injected somatostatin receptor ligand — depot octreotide or lanreotide [s2].

Paltusotine is a non-peptide selective somatostatin receptor 2 agonist developed as a once-daily oral treatment [s2]. The approved expiry dating period for Palsonify tablets is 30 months from the date of manufacture when stored at 20°C to 25°C [s1].

The substitution of a daily pill for a monthly injection is not a trivial one in either direction. It removes the injection-site burden and the clinic visit, and it hands the patient a daily adherence task in exchange.

The evidence for switching

The pivotal switching evidence was published in the Journal of Clinical Endocrinology and Metabolism in December 2024 [s2]. The phase 3, randomised, double-blind, placebo-controlled trial enrolled adults with acromegaly whose IGF-I was at or below 1.0 times the upper limit of normal while on a stable dose of depot octreotide or lanreotide [s2]. Patients were switched off the injections and randomised to oral paltusotine or placebo for 36 weeks [s2].

The primary endpoint — the proportion maintaining IGF-I at or below 1.0 times the upper limit of normal — was met: 83.3% (25 of 30) on paltusotine versus 3.6% (1 of 28) on placebo (odds ratio, 126.53; 95% CI, 13.73 to >999.99; P<0.0001) [s2].

That odds ratio, with a confidence interval whose upper bound exceeds 999.99, is a sign of a design choice rather than a miracle. Withdrawing effective therapy from people whose disease is controlled produces near-universal loss of control in the placebo arm; the comparison establishes that paltusotine does something, not how it ranks against the injection the patients came off.

Secondary endpoints all favoured paltusotine. Mean change in IGF-I was 0.04 ± 0.09 times the upper limit of normal versus 0.83 ± 0.1 on placebo (P<0.0001) [s2]. Mean change in Acromegaly Symptom Diary score was −0.6 ± 1.5 versus 4.6 ± 1.6 (P=0.02) [s2]. Mean five-sample growth hormone was maintained below 1.0 ng/mL in 20 of 23 patients (87.0%) versus 5 of 18 (27.8%) (odds ratio, 16.61; 95% CI, 2.86 to 181.36; P=0.0003) [s2].

The most common adverse events were acromegaly symptoms and the gastrointestinal effects characteristic of somatostatin receptor ligands [s2].

The safety signal FDA is tracking

The approval letter contains a request that is more informative than the approval itself. FDA asked the sponsor to submit, as 15-day alert reports, all serious and non-serious domestic and foreign cases of dry age-related macular degeneration, drusen, chorioretinopathy, central serous chorioretinopathy, retinopathy, photophobia, retinal pigment epithelium changes, and retinal pigmentation — through the fifth year following initial US approval [s1]. The agency also asked for a narrative summary and analysis of those events [s1].

This is enhanced pharmacovigilance, not a contraindication or a boxed warning. But the specificity of the list — an entire cluster of retinal and macular findings — indicates the agency saw something in the development programme it wants counted prospectively rather than left to routine reporting.

Because the drug has orphan drug designation for this indication, the sponsor is exempt from the paediatric assessment that the Pediatric Research Equity Act would otherwise require [s1].

What is not established

The trial that supports the approval enrolled patients who were already biochemically controlled on injections [s2]. It is a maintenance trial. It does not establish that paltusotine achieves control in patients who never had it, and the sample — 58 randomised patients across both arms — is small even for a rare disease.

Thirty-six weeks is also short relative to a lifelong condition, and the placebo comparator means there is no head-to-head estimate of how the pill performs against the injection patients switched from.

What to watch: the retinal event reports FDA has asked for, and whether real-world switching reproduces the trial's 83.3% maintenance rate outside a trial's monitoring.

This article is informational and is not medical advice. Decisions about acromegaly therapy are made with a clinician.

Sources

• [s1] US Food and Drug Administration, NDA 219070 approval letter, Palsonify (paltusotine) tablets, 25 September 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/219070Orig1s000ltr.pdf
• [s2] "Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine," The Journal of Clinical Endocrinology and Metabolism, December 2024. https://doi.org/10.1210/clinem/dgae385