A daily pill could soon challenge monthly depot injections as standard therapy for acromegaly in Europe.

At its February meeting, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use has recommended marketing authorization for Palsonify (paltusotine, Crinetics Pharmaceuticals) for the treatment of adults with acromegaly. 

If endorsed by the European Commission, the once-daily oral somatostatin receptor 2 (SST2) agonist would offer a clinically tested alternative to long-acting injectable therapy for this rare endocrine disorder.

The First Nonpeptide SST2 Agonist

Acromegaly is a rare chronic disorder typically caused by pituitary adenomas that secrete excess growth hormone, resulting in elevated insulin-like growth factor 1 (IGF-1) production.

Current first-line medical treatments rely on monthly depot injections of somatostatin receptor ligands such as octreotide or lanreotide, which can be associated with injection-site reactions, variable symptom control, and administration burdens.

Paltusotine acts as a highly selective SST2 agonist that mimics natural somatostatin to suppress growth hormone (GH) secretion and reduce IGF-1 levels, leading to lower — and in many cases normalized — GH and IGF-1 concentrations, potentially easing injection burden and improving convenience for patients. 

Superior Biochemical Control and Symptom Improvement

The regulatory recommendation stems from two phase 3 trials: PATHFNDR‑1 and PATHFNDR‑2.

PATHFNDR‑2 included patients who were either not receiving medical therapy or whose disease was previously controlled on long-acting injectable octreotide or lanreotide after washout. The study found that 55.7% of patients treated with paltusotine achieved biochemical control at 24 weeks vs 5.3% of patients who received placebo (P < .0001). 

In PATHFNDR‑1, which enrolled patients whose disease was biochemically controlled on injectable long-acting octreotide or lanreotide, 83.3% of those treated with paltusotine maintained biochemical control at week 36 compared with 3.6% of placebo recipients (P < .0001).

Across studies, patients who received active treatment also experienced significant symptom improvement, as measured by the Acromegaly Symptom Diary, compared with placebo recipients. Pituitary tumor volume remained stable or decreased in paltusotine-treated patients, with no clinically significant increase observed during the studies.

Safety Profile and Access

The most frequently reported adverse effects included diarrhea, abdominal pain, nausea, and abdominal discomfort. These gastrointestinal events were generally mild to moderate and resolved without treatment discontinuation, consistent with the known effects of somatostatin receptor ligands. 

Palsonify will be available as 20 mg and 30 mg film-coated tablets for once-daily oral administration. 

The drug received orphan designation during development in the European Union, and EMA will now review available data to determine whether orphan status can be maintained following authorization.

Detailed recommendations for product use will be described in the Summary of Product Characteristics, which will be published on the EMA website after the European Commission grants marketing authorization.