Paltusotine Looks Promising for Acromegaly in Phase 3 Trial

Treatment with paltusotine achieved biochemical response in insulin-like growth factor (IGF-1) for patients with acromegaly compared with placebo, according to topline results from the phase 3 PATHFNDR-2 study.

Paltusotine is an orally administered small molecule nonpeptide selective somatostatin receptor type 2 agonist. The investigational treatment is believed to maintain growth hormone (GH) and IGF-1 levels in acromegaly patients.

The randomized, placebo-controlled PATHFNDR-2 study (ClinicalTrials.gov Identifier: NCT05192382) included 111 patients with acromegaly who had elevated IGF-1 levels and were treatment naïve. Study participants were randomly assigned to receive either paltusotine orally once daily or placebo. The primary endpoint was the proportion of patients who achieve biochemical response in IGF-1 (≤1.0 times upper limit of normal [ULN]).

Findings showed 56% of patients who received paltusotine achieved an IGF-1 level equal to or less than 1 times the ULN compared with 5% of those who received placebo (P <.0001). Moreover, treatment with paltusotine achieved statistical significance for all secondary endpoints compared with placebo, respectively:

• Change from baseline in IGF-1 level (times ULN): -0.82 vs 0.09 (P <.0001);
• Proportion of participants who achieved IGF-1 level of less than 1.3 times the ULN at EoR (end of randomized control phase): 67% vs 14% (P <.0001);
• Change from baseline in Acromegaly Symptoms Diary (ASD) total score: -2.67 vs 2.75 (P =.004); and
• Proportion of participants who achieved GH level of less than 1.0ng/mL at EoR: 57% vs 18% (P <.0001).

As for safety, paltusotine was well tolerated with no serious adverse events reported. The most commonly reported treatment emergent adverse events for paltusotine were diarrhea, headache, arthralgia, and abdominal pain.

“These positive topline results of PATHFNDR-2 are incredibly exciting for both patients with acromegaly and the healthcare providers who treat them,” stated Monica R. Gadelha, MD, PhD, professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro and a principal investigator in the PATHFNDR program. “This study demonstrates that paltusotine can provide both symptom control as well as biochemical control in patients who are not currently on pharmacologic treatment. If approved, the prospect that paltusotine can offer an innovative, once-daily oral alternative represents a significant step forward in improving the treatment experience for patients.”