Camurus announced positive topline results from its POSITANO Phase 2b study, demonstrating that CAM2029, an octreotide subcutaneous depot, significantly reduces liver and cyst volumes in patients with symptomatic polycystic liver disease (PLD). The 12-month, randomized, double-blind, placebo-controlled trial represents a potential breakthrough for a rare genetic disorder that currently has no approved treatment options.
Primary Endpoint Achievement
The POSITANO study enrolled 71 participants with symptomatic PLD, randomized to treatment with one of two dosing regimens of CAM2029 or placebo in a 1:1:1 ratio. The study met its primary endpoint, showing a statistically significant relative reduction of height-adjusted liver volume (htTLV) from baseline to week 53 of 4.3% (p=0.044) for the combined CAM2029 groups compared to placebo. The corresponding relative reduction in total liver cyst volume was even more pronounced at 8.7% (p=0.016).
"The POSITANO study shows that CAM2029 significantly reduces liver and liver cyst volume compared to placebo while showing improvements in symptoms as assessed by relevant patient reported outcomes," said Dr. Joost P.H. Drenth, Professor of Hepatology at Amsterdam University Medical Center and coordinating investigator for the POSITANO study. "There is a high unmet medical need for treatment of patients with polycystic liver disease and the POSITANO study brings hope for our patients."
Addressing Significant Unmet Medical Need
PLD is a rare genetic disorder causing progressive liver cysts, leading to severe symptoms and reduced quality of life. Approximately 37,000 people in the US and EU have PLD, with women representing the majority of symptomatic patients. The condition is characterized by progressive growth of fluid-filled cysts in the liver, causing severe symptoms including abdominal pain and discomfort, shortness of breath, indigestion, gastro-esophageal reflux, and limited mobility.
Most patients with PLD are diagnosed in their 30s after reporting a sudden and accelerated increase of waist width together with PLD-related symptoms. Age and gender contribute to disease severity, with increasing age positively associated with both cyst sizes and numbers, and women highly overrepresented among symptomatic patients.
Safety Profile and Tolerability
CAM2029 demonstrated a favorable safety profile consistent with established somatostatin receptor ligands. The treatment was well tolerated, with the most frequently reported adverse effects being diarrhea, mild to moderate gastrointestinal disturbances, and injection site reactions. No new or unexpected safety findings were noted during the study period.
Development Program and Regulatory Status
CAM2029 is a ready-to-use, long-acting subcutaneous depot of octreotide designed for enhanced octreotide exposure and convenient, once-monthly administration with a prefilled autoinjector pen to facilitate easy self-administration by patients. The drug has been granted Orphan Drug Designation for the treatment of autosomal dominant PLD in both the US by the FDA and in the EU by the European Commission.
"The POSITANO study met the primary endpoint showing that CAM2029 reduces liver and cyst growth and can improve disease symptoms and other outcomes in patients with polycystic liver disease," said Fredrik Tiberg, Camurus' President & CEO, CSO. "Based on the results, Camurus intends to discuss the design of a confirmatory Phase 3 study with regulatory authorities in the US and Europe."
Ongoing Research and Future Plans
Following completion of the randomized portion of POSITANO, patients continue treatment with CAM2029 in a 2.5-year open extension phase where additional long-term efficacy and safety data are being collected. Detailed results from the POSITANO study will be presented at future scientific meetings and in publications.
CAM2029 has been evaluated in a comprehensive clinical program beyond PLD, including development for acromegaly and gastroenteropancreatic neuroendocrine tumors, with multiple Phase 1, 2, and 3 studies completed or ongoing across these indications.
