A pill for acromegaly held disease control for up to four years in a small study

Paltusotine, the first once-daily oral drug for acromegaly, kept the disease under control for up to four years in patients who had switched to it from monthly injections, according to an open-label extension study [s1]. Median levels of IGF-I — the hormone used to track the disease — sat near the top of the normal range from the start of the extension through week 207, and growth hormone, symptoms and tumour size stayed stable [s1]. The caveats are structural: the extension had no comparison group, and only 20 of the original 43 patients were still contributing data at that final timepoint [s1].

Acromegaly is caused by a pituitary tumour that oversecretes growth hormone, driving up IGF-I and, over years, enlarging bones and soft tissue and raising cardiovascular and metabolic risk. For three decades the mainstay of drug treatment has been a class of injected somatostatin receptor ligands, given every four weeks. Paltusotine is a non-peptide drug in the same mechanistic family, taken as a daily tablet; the US Food and Drug Administration approved it in September 2025 for adults whose disease did not respond adequately to surgery or who cannot have surgery [s3].

What the extension tested

The question a daily pill has to answer for a lifelong disease is not whether it works for a few months but whether control holds for years. ACROBAT Advance is an ongoing open-label extension that enrolled patients who had completed one of two earlier phase 2 studies, and the paper reports interim results out to year 4 [s1]. Forty-three patients — 88% of those eligible from the parent trials — entered the extension [s1]. The maximum dose was initially 40 mg and rose to 60 mg once a tablet formulation became available in the third year, and patients could add the drugs cabergoline or pegvisomant if clinically needed [s1].

What it showed

Median IGF-I was 1.15 times the upper limit of normal at the parent-study baseline, 1.17 times the limit at week 3 of the extension, and 1.01 times the limit at week 207 [s1]. Those medians describe a group held around the normal ceiling rather than pushed well below it, which is the goal of treatment. Growth hormone levels, acromegaly symptoms and pituitary tumour size all remained stable, and the drug was well tolerated with no unexpected safety findings [s1]. Eight patients (18.6%) had discontinued by the time of the analysis, including two (4.7%) because of adverse events [s1].

The short-term case for the switch was made earlier, in the randomised trial that supported approval. In that study 83.3% of patients (25 of 30) on paltusotine maintained IGF-I at or below the normal limit, versus 3.6% (1 of 28) on placebo, after switching from injected therapy [s2]. Growth hormone was kept below 1.0 ng/mL in 87.0% of the paltusotine group against 27.8% on placebo [s2]. The extension's contribution is the durability question that a placebo-controlled switch trial, by design, could not address.

How to read a four-year single-arm result

The numbers are reassuring on their face, and they should be read with the study's design in mind. An open-label extension has no control group, so there is nothing to compare the maintained IGF-I against; patients and investigators knew everyone was receiving the active drug [s1]. The cohort is small, and attrition matters: the week-207 median rests on 20 patients, fewer than half the 43 who started, and people who do well are generally likelier to stay in an extension than people who do not [s1]. Some patients were also allowed additional acromegaly drugs during follow-up, so the result describes a treatment strategy built around paltusotine rather than the pill in isolation [s1]. The study was conducted and funded by the drug's manufacturer, Crinetics Pharmaceuticals, whose employees are among the authors [s1].

None of that makes the signal unreal. It means the appropriate reading is that daily oral paltusotine maintained biochemical and symptom control over several years in a selected group who had already tolerated and responded to it — a genuine and useful finding for a disease treated for life, and one short of the evidence a randomised long-term comparison against injected therapy would provide.

What to watch

Longer follow-up with more of the cohort retained; whether real-world control matches the trial once the drug is used outside a study; and how oral and injected somatostatin ligands compare head to head on control, tumour size and quality of life over years rather than months.

This article describes trial results and a regulatory approval and is informational only. It is not medical advice and does not recommend any drug. Acromegaly treatment is a matter for a specialist.

Sources

• [s1] Gadelha MR, Gordon MB, Doknic M, Mezősi E, Tóth M, Randeva H, Boguszewski CL, Davidson C, Casagrande A, Jochelson T, Krasner A, Safety and Efficacy of Once-Daily Oral Paltusotine in Acromegaly: ACROBAT Advance Open-Label Extension Up to 4 Years, The Journal of Clinical Endocrinology and Metabolism, published online 2026-06-26.
• [s2] Gadelha MR, et al., Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine, The Journal of Clinical Endocrinology and Metabolism, published online 2024-06-03.
• [s3] US Food and Drug Administration, NDA 219070 approval letter, Palsonify (paltusotine) tablets, Center for Drug Evaluation and Research, 2025-09-25.