Paltusotine Meets All Goals in Phase 3 Acromegaly Trial

Crinetics Pharmaceuticals, a clinical-stage pharmaceutical company, has announced the successful results of a Phase 3 study for paltusotine, a new oral treatment for acromegaly. The drug showed significant efficacy and safety in reducing IGF-1 levels, a key biomarker for the disease, with 56% of patients on paltusotine achieving the target level compared to just 5% on a placebo. The study also reported that paltusotine was well-tolerated with no serious adverse events, marking a significant step forward in the treatment of acromegaly.

The study, known as PATHFNDR-2, was a randomized, double-blind, placebo-controlled trial that included 111 participants. It followed a 24-week treatment period with an optional open-label extension. The primary endpoint was the proportion of patients achieving an IGF-1 level of less than or equal to 1.0 times the upper limit of normal (xULN). The results were statistically significant, with a p-value of less than 0.0001.

Secondary endpoints also showed significant improvements, including changes in IGF-1 levels, the proportion of participants achieving an IGF-1 level of less than 1.3 xULN, changes in Acromegaly Symptoms Diary scores, and the proportion of participants achieving a growth hormone level of less than 1.0ng/mL.

Dr. Monica R. Gadelha, a principal investigator in the PATHFNDR program, highlighted the importance of these results for patients and healthcare providers. She emphasized that paltusotine could offer symptom and biochemical control for patients not currently on pharmacological treatment, and its potential approval could provide an innovative, once-daily oral alternative.

In the PATHFNDR-2 study, paltusotine demonstrated a favorable safety profile, with the frequency of treatment emergent adverse events comparable between the paltusotine and placebo groups. The most common adverse events included diarrhea, headache, joint pain, and abdominal pain.

Scott Struthers, CEO of Crinetics, expressed enthusiasm for the study's outcomes and the potential of paltusotine to become a new treatment option for acromegaly patients. The company plans to submit a New Drug Application (NDA) to the FDA in the second half of 2024, with a potential launch in 2025.

Acromegaly is a serious rare disease caused by a pituitary adenoma that leads to excess secretion of growth hormone and IGF-1, causing various systemic complications. Current treatments include surgery and pharmacotherapy with injectable somatostatin analogues, which can be burdensome for patients.

Paltusotine is an oral, once-daily somatostatin receptor type 2 (SST2) agonist, designed to provide an effective and convenient treatment option for acromegaly and carcinoid syndrome. The drug is also in Phase 2 studies for carcinoid syndrome.

Crinetics Pharmaceuticals is dedicated to developing novel therapeutics for endocrine diseases and tumors. In addition to paltusotine, the company is developing CRN04894, an oral ACTH antagonist for congenital adrenal hyperplasia and Cushing’s disease, as well as other programs targeting various endocrine conditions.

The company will host a conference call on March 19 to discuss the PATHFNDR-2 results and future plans for paltusotine.