Crinetics Unveils New ENDO 2024 Data Supporting Paltusotine as Leading Acromegaly Treatment

Crinetics Pharmaceuticals has presented new data at the Endocrine Society's Annual Meeting (ENDO2024) from its clinical development program for paltusotine, an investigational treatment for acromegaly. Paltusotine is a once-daily oral medication aimed at addressing both biochemical markers and symptoms associated with this condition.

The Phase 3 PATHFNDR-2 trial was highlighted, showing significant efficacy of paltusotine. This randomized, double-blind, placebo-controlled study involved 111 participants with active acromegaly who had not been treated pharmacologically. The trial met its primary endpoint, with 56% of participants on paltusotine achieving normalized insulin-like growth factor 1 (IGF-1) levels, compared to only 5% in the placebo group. The majority of the IGF-1 reduction occurred within the first few weeks of treatment and was sustained throughout the 24-week period. Paltusotine was generally well-tolerated, with adverse events like diarrhea, headache, and abdominal pain being most common, though no serious adverse events were reported.

In addition to PATHFNDR-2, Crinetics presented a new patient-reported outcome analysis from the Phase 3 PATHFNDR-1 trial. This study involved participants switching from injected somatostatin receptor ligands (SRL) to paltusotine. The Acromegaly Symptom Diary (ASD) was used to assess symptom burden. Patients reported fewer breakthrough symptoms on paltusotine, including improvements in fatigue, headache, joint pain, and sleep difficulties, compared to their previous treatment with injected medications. This suggests that paltusotine may offer a more stable day-to-day symptom control for acromegaly patients.

The long-term safety and efficacy of paltusotine were also supported by data from the ACROBAT Advance extension study. This ongoing six-year trial includes patients who had completed earlier Phase 2 studies. Interim results indicate that paltusotine continues to be well-tolerated over long-term use, with stable control of IGF-1 levels and acromegaly symptoms. Adverse events reported were consistent with those observed in prior studies, with the most common being arthralgia, headache, and fatigue.

Given these promising results, Crinetics plans to submit a New Drug Application (NDA) to the FDA in the second half of 2024, aiming to offer paltusotine as a new treatment option for acromegaly. The drug has shown potential not only in controlling biochemical markers but also in reducing the burden of symptoms and treatment-related discomfort compared to current standard-of-care injections.

Paltusotine is a novel somatostatin receptor type 2 (SST2) agonist, designed to be a more convenient once-daily oral alternative to injectable therapies. In previous studies, including Phase 2 trials for carcinoid syndrome, paltusotine effectively maintained IGF-1 levels in patients switching from monthly injections.

Acromegaly, typically caused by a benign pituitary tumor, leads to excessive secretion of growth hormone (GH) and IGF-1. This results in severe complications affecting various body systems and significantly impairs quality of life. Surgical removal of the pituitary tumor is the first-line treatment, but many patients require pharmacotherapy when surgery is not viable or successful. Current injectable treatments are effective but associated with significant drawbacks, including pain and injection site reactions.

Crinetics Pharmaceuticals focuses on developing novel therapeutics for endocrine diseases and tumors. Their pipeline includes paltusotine for acromegaly and carcinoid syndrome and atumelnant for congenital adrenal hyperplasia and Cushing’s syndrome. All drug candidates are orally administered, small molecule entities developed through in-house research.

This comprehensive data underscores the potential of paltusotine to transform acromegaly treatment, offering both efficacy and patient convenience, and marks a significant step forward in Crinetics' drug development efforts.