Crinetics Launches CAREFNDR Trial to Evaluate Paltusotine's Potential in Carcinoid Syndrome Management

Crinetics Pharmaceuticals has commenced a landmark Phase 3 clinical investigation assessing Paltusotine as a treatment option for carcinoid syndrome in adult patients. The multicenter trial, designated CAREFNDR, reflects the company’s expansion of PALSONIFY (Paltusotine) beyond its currently approved application in acromegaly, where the drug demonstrated strong efficacy following FDA approval in September 2025.

Understanding the Clinical Need

Carcinoid syndrome emerges in approximately one-fifth of patients diagnosed with neuroendocrine tumors, predominantly occurring when malignancies metastasize to the liver. Patients frequently experience debilitating symptoms including flushing episodes and chronic diarrhea, which substantially compromise daily functioning and quality of life. Existing treatment protocols rely on monthly injectable medications that often fail to deliver adequate symptom control, creating a meaningful gap in therapeutic options for affected populations.

CAREFNDR Trial Design and Objectives

The study will enroll 141 adult participants in a double-blind, randomized, placebo-controlled design. Participants will be assigned to receive either Paltusotine 80 mg administered orally once daily or placebo over a 16-week intervention period. The investigation will primarily assess the reduction in daily flushing episodes from baseline measurement through week 12. Secondary outcomes will evaluate changes in bowel movement frequency alongside other clinically relevant endpoints.

Following the controlled treatment phase, enrolled patients will transition into an extended open-label period spanning 104 weeks to evaluate sustained efficacy, safety profile, and long-term tumor control outcomes.

Mechanism and Prior Evidence

Paltusotine operates through selective targeting of somatostatin receptor type 2 (SST2), a mechanism that has proven effective in previous Phase 2 investigations. Earlier studies demonstrated rapid, durable improvements in both flushing frequency and bowel movement patterns, suggesting meaningful clinical benefit for patients constrained by the practical limitations of injectable therapies. The oral once-daily formulation offers potential advantages in treatment adherence and patient convenience compared to current standard-of-care regimens.

Company Pipeline and Financial Position

Beyond the CAREFNDR investigation, Crinetics is progressing CRN09682, a Phase 1/2 program evaluating an investigational SST2-targeting therapeutic for solid tumors expressing neuroendocrine features. The company also anticipates advancing multiple studies in 2025 and 2026, including enrollment initiation for the CALM-CAH Phase 3 trial examining Atumelnant in congenital adrenal hyperplasia, with additional studies planned for pediatric populations and Cushing’s syndrome indications.

As of September 30, 2025, the company maintained a cash position of $1.1 billion, providing runway to sustain operations through 2029 based on current spending projections.

Market Performance

CRNX shares have fluctuated between $24.10 and $60.34 over the preceding 12 months. Most recent trading activity showed the stock closing at $41.97, representing a 2.17% decline, with after-hours movement to $41.98 reflecting modest gains of 0.02%.