A daily oral investigational drug has shown a significant ability to help patients with acromegaly maintain their insulin-like growth factor (IGF-1) levels. Paltusotine, developed by Crinetics Pharmaceuticals, demonstrated statistically significant improvements in primary and secondary efficacy measures during the phase 3 PATHFNDR-1 trial. This 36-week assessment, including an open-label extension, compared paltusotine to a placebo in patients with the rare condition of excessive growth hormone (GH) production.
These findings suggest a promising path for paltusotine to become a groundbreaking treatment for acromegaly, a severe and potentially life-threatening disease that significantly affects daily life and well-being. It offers a less invasive alternative for patients.
According to a statement from Crinetics, the randomized, double-blind, placebo-controlled PATHFNDR-1 trial produced significant positive outcomes with paltusotine. In this study, which is one of two ongoing phase 3 evaluations of the daily oral drug in acromegaly patients transitioning from standard-care injection therapy, the drug was assessed in patients previously controlled with octreotide or lanreotide depot monotherapy. Of the 58 adult patients enrolled, the primary endpoint was the proportion of patients maintaining their IGF-1 levels after switching to paltusotine following 36 weeks of treatment.
Patients were randomized to either treatment (n = 30) or placebo (n = 28) during the treatment period and were given the option to participate in an open-label extension assessment of paltusotine if they were switching from somatostatin analogs.
Crinetics reported that 25 (83%) patients receiving paltusotine achieved the primary endpoint of maintaining IGF-1 levels below 1.0 times the upper limit of normal (ULN) after 36 weeks, compared to only 1 (4%) of patients receiving the placebo (P <.0001).
Additionally, investigators observed significant improvements in three key secondary endpoints:
1. Mean change from baseline IGF-1 level (0.04x ULN vs. 0.83x ULN; P <.0001)
2. Mean change from baseline in Acromegaly Symptoms Diary Score (-0.6 vs. 4.6; P = .02)
3. Proportion of patients who maintained GH levels below 1.0 ng/mL (20 [87%] vs. 5 [18%]; P = .0003).
Data from PATHFNDR-1 also indicated that paltusotine was well-tolerated, with no reports of serious or severe adverse events among participants treated with the drug. The most commonly reported treatment-related side effects included arthralgia, headache, diarrhea, abdominal pain, and nausea, each reported in fewer than 30% of treated patients.
While awaiting a comprehensive, peer-reviewed analysis of PATHFNDR-1, to be presented at upcoming scientific conferences, Crinetics executives and investigators expressed their enthusiasm for these significant outcomes. They believe that paltusotine, if approved, could provide a much-needed, simple, oral, once-daily therapy for acromegaly patients, reducing the burden of injections. The company intends to seek regulatory approval as quickly as possible, pending the completion of the PATHFNDR-2 study early next year.
Sherwood, A. (2023, September 10). Crinetics’ once-daily oral paltusotine achieved the primary and all secondary endpoints in the Phase 3. Crinetics Pharmaceuticals - Developing Therapies for Rare Endocrine Diseases.