SAN DIEGO, Calif. — Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, today announced positive topline results from PATHFNDR-2, the second of two Phase 3 studies evaluating the efficacy and safety of oral, once-daily investigational paltusotine for the treatment of acromegaly.
PATHFNDR-2 (NCT05192382) was a randomized, double-blind, placebo-controlled 24-week treatment period followed by an optional open-label extension study evaluating paltusotine in 111 participants with acromegaly who were not pharmacologically treated. The study met statistical significance (p<0.0001) on the primary endpoint, based on the proportion of participants taking paltusotine (56%) who achieved an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the upper limit of normal (xULN) compared to those taking placebo (5%). All secondary endpoints also met statistical significance.
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, M.D., Ph.D., 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.”
In PATHFNDR-2, paltusotine was generally well-tolerated and no serious adverse events were reported in participants treated with paltusotine. The frequency of participants with at least one treatment emergent adverse event (TEAE) was comparable in the paltusotine treatment arm and placebo arm. The most commonly reported TEAEs in paltusotine-treated participants included: diarrhea, headache, arthralgia and abdominal pain. The frequency of adverse events considered related to acromegaly was notably lower in paltusotine treated participants compared to placebo treated participants.
“Paltusotine continues to exceed expectations. Today, PATHFNDR-2 delivered statistically significant topline results across the board,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “Building upon the success of PATHFNDR-1, the totality of data underscores the potential of paltusotine to provide an important new treatment option for all people living with acromegaly, if approved. We intend to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration in the second half of 2024, and our team is actively preparing for a potential 2025 launch. We are deeply grateful to all the individuals who participated in this study, the skilled clinical staff who provided exceptional care, and the dedicated Crinetics team from around the globe. This collective endeavor has brought an important new potential acromegaly treatment option closer to becoming a reality.”
About the PATHFNDR Program
The PATHFNDR Program consists of two Phase 3 double-blind, placebo-controlled studies. PATHFNDR-1 (NCT04837040) enrolled a total of 58 adults with acromegaly who entered with an IGF-1 level ≤ 1.0x ULN on octreotide or lanreotide depot monotherapy. The participants were randomized to receive once-daily, oral paltusotine for 36 weeks or placebo. PATHFNDR-2 (NCT05192382) enrolled 111 adults with acromegaly who had elevated IGF-1 levels but were medication naïve or were not being treated with pharmacotherapy (untreated patients).
The primary endpoint for both studies is the proportion of patients achieving IGF-1 ≤1.0 xULN compared to placebo. Crinetics believes these studies could support registration of paltusotine in the United States and Europe for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from standard of care.
About Acromegaly
Acromegaly is a serious rare disease generally caused by a pituitary adenoma, a benign tumor in the pituitary that secretes growth hormone (GH). Excess GH secretion causes excess secretion of IGF-1 from the liver. Prolonged exposure to increased levels of IGF-1 and GH leads to progressive and serious systemic complications, often resulting in bone, joint, cardiovascular, metabolic, cerebrovascular, or respiratory disease. Acromegaly symptoms include headache, joint aches, fatigue, sleep apnea, severe sweating, hyperhidrosis/oily skin, bone and cartilage overgrowth, abnormal growth of hands and feet, enlargement of heart, liver, and other organs and alteration of facial features. Uncontrolled acromegaly results in increased mortality and has a debilitating impact on daily functioning and quality of life.
Surgical removal of pituitary adenomas, if possible, is the preferred initial treatment for most acromegaly patients. Pharmacotherapy is used for patients who are not candidates for surgery, or when surgery is unsuccessful in achieving treatment goals. Approximately 50% of patients with acromegaly prove to be candidates for pharmacotherapy. Injectable depot somatostatin analogues are the most common initial pharmacologic treatment; however, these drugs require monthly depot injections with large gauge needles that are commonly associated with pain, injection site reactions, and an increased burden on the lives of patients.
About Paltusotine
Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist and is currently in investigational Phase 3 studies for acromegaly and a Phase 2 study for carcinoid syndrome. It was designed by the Crinetics’ discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In Phase 2 studies and the recently completed PATHFNDR-1 Phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome further support paltusotine’s potential use beyond acromegaly.
About Crinetics Pharmaceuticals
Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894, an investigational, first-in-class, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of congenital adrenal hyperplasia and Cushing’s disease. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity.
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