A Randomised, Double-Blind, Non-Inferiority Trial Comparing Microbial and Porcine Pancreatic Enzyme Replacement Therapy in Chronic Pancreatitis

Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas. It is characterized by persistent inflammation that progressively damages the pancreatic tissue, leading to irreversible fibrotic changes. The dominant clinical manifestation of is abdominal pain and ongoing parenchymal injury leads to a gradual decline in both exocrine and endocrine function. However, the onset of pancreatic exocrine insufficiency (PEI) and diabetes is not universal, as a subset of individuals with CP retains sufficient exocrine reserve to avoid clinically significant malabsorption. When functional decline advances, however, patients may ultimately develop PEI and diabetes. In the absence of disease-modifying treatments, the current primary goal of management is early recognition and management of these complications. Treatment includes pain management, digestive support with pancreatic enzyme supplementation and nutrition, and endocrine management with oral antidiabetic medications and/or insulin.

In PEI, insufficient secretion of pancreatic enzymes leads to inadequate digestion and absorption of nutrients, resulting in weight loss, malnutrition, metabolic bone disease, and deficiencies of fat-soluble vitamins and minerals. PEI develops frequently in patients with CP, with a prevalence ranging from 30%-85% within 10-15 years after diagnosis.

Large cohort studies report an overall PEI prevalence of 50%-75%, particularly in patients with alcohol-related CP and longer disease duration. Management of PEI secondary to CP is important to improve nutritional status and quality of life. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for PEI. According to two meta-analyses, supportive treatment with pancreatic enzyme replacement showed significant improvement in the symptoms and consequences of PEI in patients with CP.

Currently available PERT preparations are primarily derived from porcine pancreas. Although clinically effective, porcine-derived PERT has certain limitations, including concerns related to its animal origin. Additionally, some patients may avoid such supplements due to lifestyle or ethical choices, such as vegetarians and vegans, while others, particularly followers of Islam and Judaism, may refrain from porcine-derived products due to religious dietary restrictions. Importantly, there is an increased lack of supplies due to the increasing prevalence of CP and other diseases associated with PEI. Therefore, new formulations of PERT are an unmet need.

Advances in biotechnology have led to the development of non-porcine microbial (fungal) based pancreatic enzymes that have been shown to have a good safety profile and efficacy in several conditions. Animal studies and human pilot studies have also shown benefit in CP. While the use of porcine PERT is well-established in CP, the utilization of non-porcine microbial-based PERT and its efficacy in CP is unclear.