Advancing treatment for polycystic liver disease: Insights from the POSITANO trial

touchIMMUNOLOGY coverage of EASL 2026

What is the burden of polycystic liver disease (PLD) for patients and what unmet needs exist in its treatment?

Polycystic liver disease (PLD) is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD), but it can also occur as a separate inherited disorder, autosomal dominant polycystic liver disease (ADPLD). The prevalence of clinically significant PLD is difficult to define precisely because many patients remain asymptomatic for years. Some liver cysts are detectable in up to 80–90% of adults with ADPKD by the age of 40–50 years using modern imaging techniques, but PLD is much more infrequent.

Isolated ADPLD is considered a rare disease and has an estimated prevalence of approximately 1 in 10,000. PLD preferentially affects females, and symptomatic disease resulting from hepatomegaly develops in mid-adulthood. It should be mentioned that only a minority of patients will develop severe symptomatic hepatomegaly requiring medical or interventional treatment. PLD can cause symptoms such as abdominal distension, early satiety, dyspnea, pain, reduced mobility, and lower quality of life.

The key unmet need is that there is no approved pharmacological treatment for PLD; current options are mainly conservative care or invasive procedures, while liver transplantation is only reserved for the most severe cases.

Could you describe the mechanism of action of CAM2029?

CAM2029 is a newly developed octreotide subcutaneous depot, a somatostatin receptor ligand. Somatostatin analogues (such as octreotide and lanreotide) are thought to combat PLD by interfering with the abnormal biology of cyst-lining cholangiocytes.

In PLD, cholangiocytes exhibit increased proliferation and enhanced secretion of chloride-rich fluid into cysts, both of which contribute to progressive cyst enlargement. A central driver of this process is elevated intracellular cyclic AMP (cAMP) signaling.

Somatostatin analogues bind mainly to somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) on cholangiocytes. Activation of these receptors inhibits adenylate cyclase activity, leading to reduced intracellular cAMP levels. Lower cAMP signaling has several downstream effects such as reduced cyst fluid secretion and reduced cholangiocyte proliferation as well as impaired growth signaling through pathways such as MAPK/ERK. The combined result is slowing of cyst expansion and stabilization or reduction of liver volume.

What were the aims and design of the phase 2b POSITANO study?

POSITANO was a phase 2b, randomized, placebo-controlled, double-blind, multicenter study in patients with symptomatic PLD (height adjusted total liver volume [htTLV] > 1800 mL/m). Seventy-one patients were randomized 1:1:1 to CAM2029 10 mg once weekly, CAM2029 10 mg every 2 weeks, or placebo for 52 weeks, followed by an ongoing open-label extension. MRI was used to determine htTLV. The primary endpoint was difference in htTLV from baseline to Week 53 between CAM2029 (combined doses) and placebo.

Could you tell us about the efficacy and safety findings?

The study met its primary endpoint: the combined CAM2029 arms showed a significant relative treatment difference in htTLV versus placebo of −4.3% at Week 53. Total liver cyst volume also favored CAM2029. PLD symptom scores improved within CAM2029 groups, though the key secondary symptom comparison versus placebo was not statistically significant. Safety was consistent with injectable somatostatin analogues; common adverse events were diarrhea, injection-site pain, and injection-site pruritus, with no new or unexpected safety findings.

What are the current status and next steps in the development of CAM2029?

The double-blind period is complete, and the open-label extension is ongoing. The next steps are to complete the open label extension phase, further define durability of effect and safety, and use these data to guide the next phase of clinical development.

Somatostatin analogues are likely to remain an important tool in the management of patients with symptomatic, severe PLD.  Clinically, the effect is usually disease stabilization rather than dramatic shrinkage. The current therapeutic goal is therefore often to slow progression, reduce liver enlargement, and improve symptom burden over time rather than cure the disease.

One important limitation is that the effect tends to persist only while treatment continues; discontinuation may allow cyst growth to resume. This is why long-acting formulations and better-tolerated delivery systems are an important area of development in PLD therapy.