The FDA has accepted Crinetics Pharmaceuticals' New Drug Application (NDA) for paltusotine, an investigational drug for the treatment and long-term maintenance therapy of acromegaly in adult patients. This acceptance marks a significant step toward potentially providing the first once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist for individuals living with acromegaly. The FDA has set a Prescription Drug User Fee target action date of September 25, 2025, for completing its review.
Clinical Data Supporting the NDA
The NDA submission included data from the PATHFNDR-1 (NCT04837040) and PATHFNDR-2 (NCT05192382) Phase 3 clinical trials. These trials evaluated the safety and efficacy of paltusotine in adults with acromegaly, both in previously treated and medically untreated populations.
Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics, stated, "With our patient-centered clinical development of paltusotine, we were guided by an unwavering ambition to deliver a new generation of treatment that provides a once-daily, oral alternative to the currently marketed peptide analog drugs."
Addressing Unmet Needs in Acromegaly Treatment
Acromegaly is a serious rare disease typically caused by a benign pituitary adenoma that secretes excess growth hormone (GH). This leads to excess secretion of insulin-like growth factor-1 (IGF-1) from the liver, resulting in progressive systemic complications affecting bone, joints, cardiovascular, metabolic, cerebrovascular, and respiratory systems. Symptoms include headache, joint aches, fatigue, sleep apnea, severe sweating, and abnormal growth of hands and feet. Current treatments often involve monthly depot injections of peptide somatostatin receptor ligands, which can be burdensome due to administration difficulties, pain, and fluctuating symptom control.
Paltusotine aims to address these limitations by offering a convenient oral administration route and potentially improved symptom management. In Phase 3 studies, once-daily oral paltusotine maintained IGF-1 levels and symptom control in patients switched from injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated patients (PATHFNDR-2).
Orphan Drug Designation and Future Development
Paltusotine was granted Orphan Drug Designation by the FDA in July 2020, a status reserved for drugs intended for the safe and effective treatment of rare diseases affecting fewer than 200,000 people in the United States. This designation provides certain benefits, including market exclusivity upon approval.
Crinetics is also preparing to initiate a Phase 3 trial for the control of symptoms associated with carcinoid syndrome in patients with neuroendocrine tumors, further expanding the potential applications of paltusotine.
