LAS VEGAS — The once-daily oral paltusotine (Palsonify, Crinetics Pharmaceuticals) showed efficacy and safety for the treatment of acromegaly in the first few patients to receive it post approval.

And in a post hoc analysis of phase 3 clinical trial data, there was no evidence of interaction between paltusotine and levothyroxine in patients taking both drugs.

“As an oral once-daily, it’s very convenient for patients. Plus, it’s very effective from what we can tell from the trials. The patients I’ve treated have had great results, within 2-4 weeks. Also, it has a great effect on symptom control regardless of baseline [insulin-like growth factor [IGF]-1] level,” study investigator Leena Shahla, MD, of Duke University, Durham, North Carolina, told Medscape Medical News.

Treatment options for acromegaly, a condition of excess growth hormone usually due to a pituitary tumor, include surgery to remove pituitary tumors, radiation therapy, and medications such as somatostatin receptor ligands (SRLs) that require monthly injections (octreotide, lanreotide, and pasireotide), a growth hormone receptor antagonist (pegvisomant), and a dopamine receptor agonist (cabergoline).

Paltusotine, a selective somatostatin 2 receptor agonist, was approved by the FDA in September 2025 for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. It is the first oral nonpeptide drug available for treating the condition.

At the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026, Shahla, who is both an endocrinologist and neuroendocrinologist at Duke, presented data for six patients who received paltusotine at three US-based pituitary centers between October 2025 and January 2026. Three were patients she treated.

The six patients included three men and three women, ranging in age from 25 to 58 years. All had undergone prior resection of the pituitary adenoma, two with repeat surgeries. Three patients had not previously received an acromegaly medication, whereas the other three had received treatments including carbergoline, lanreotide, and/or ocreotide but had discontinued them. One who had discontinued lanreotide continued to use pegvisomant while on paltusotine. The paltusotine dose was 20-40 mg/d.

Baseline IGF-1 levels ranged from 304 ng/mL to 674 ng/mL. At 3-4 weeks after initiation of paltusotine, IGF-1 levels normalized in all but one patient, dropping to 164-281 ng/mL. Across centers, the upper limit of normal for IGF-1 ranged from 328 ng/mL to 347 ng/mL. The one patient whose IGF-1 level didn’t change was suspected of noncompliance, Shahla said.

In three of the patients for whom paltusotine was used as first-line medical therapy, IGF-1 levels dropped from 621 ng/mL to 275 ng/mL, 304 ng/mL to 211 ng/mL, and 674 ng/mL to 164 ng/mL.

Patients had a spectrum of presenting signs and symptoms, with varying patterns of improvements with paltusotine. Among three patients who had headaches at baseline, one had resolution of symptoms and two had improvement. Of three with sleep apnea at baseline, two had improved sleep with the drug. Joint pain resolved in two patients who had it at baseline. Other improvements were seen in blood pressure, menstrual regularity, energy, and sweating.

Gastrointestinal adverse events, including nausea, diarrhea, and abdominal pain, were reported in five of the six patients but improved or resolved with continued paltusotine exposure over time. No patient discontinued paltusotine due to adverse events. One patient required a dose reduction due to diarrhea, which subsequently improved.

“These preliminary data suggest that paltusotine may be efficacious in a broad spectrum of patients with varied treatment histories, including patients who are prescribed paltusotine as first-line medical therapy after surgery, after failed treatment with cabergoline and/or injected depot SRLs, and as add-on therapy to pegvisomant,” said Shahla.

She acknowledged, however, that “additional real-world studies with larger sample sizes are needed.”

Asked to comment, session moderator Catherine Anastasopoulou, MD, PhD, associate professor of medicine at Sidney Kimmel Medical College of Jefferson University, Philadelphia, told Medscape Medical News that she hasn’t yet had a chance to prescribe paltusotine, but she agrees the data look good so far.

“Acromegaly is a very rare disease, so we don’t have that many patients in our practices. And most of the time, we are going to start with the long-term standard of care…But this particular medicine sounds very promising and much easier to take. I was impressed with the results. So hopefully we will use it more clinically and then learn if it can be a good choice to even bypass some of the previous medications for acromegaly treatment,” Anastasopoulou said.

Interactions With Levothyroxine?

In a separate presentation at the meeting, Raffaella M. Colzani, MD, of Crinetics Pharmaceuticals, reported an ad hoc analysis of phase 3 clinical trial data from the PATHFNDR-1 and PATHFNDR-2 trials, which were conducted to determine the effect of concomitant use of levothyroxine on IGF-1 levels in patients who were also taking paltusotine.

The concern is that somatostatin analogs can suppress thyroid-stimulating hormone (TSH), which could lead to hypothyroidism, therefore periodic assessment of thyroid hormones is recommended for patients treated with SRLs.

The analysis included 43 patients who were taking levothyroxine with either paltusotine (n = 25) or placebo (n = 18) during the trials.

Both paltusotine and levothyroxine should be taken on an empty stomach about 1 hour before eating, Colzani said. 

This recommendation was followed in the phase 3 trials, but no guidance was given regarding the timing of levothyroxine relative to paltusotine, she noted.

Both TSH and free thyroxine remained stable in both the paltusotine and placebo groups at baseline and end of treatment (36 weeks in PATHFNDR-1 and 24 weeks in PATHFNDR- 2). In PATHFINDR-1, IGF-1 levels remained stable in patients who switched from an injected depot SRL to paltusotine, regardless of whether they were also taking levothyroxine (n = 9 were taking both; n = 19 were taking paltusotine alone).

Based on these results, “there is no evidence that paltusotine directly interacts with levothyroxine,” Colzani concluded.

Shahla reported serving as a consultant to Camurus, Chiesi Farmaceutici, Crinetics Pharmaceuticals, Inc., and Recordati Rare Diseases. Colzani reported being a Crinetics employee. Anastasopoulou reported having no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.