Source – First Wave BioPharma
First Wave BioPharma, formerly known as AzurRx BioPharma, has faced ongoing challenges in bringing a new drug to the market to address pancreatic insufficiency in cystic fibrosis patients. Despite reformulating its candidate drug, adrulipase, and conducting the Phase II SPAN trial with an enteric microgranule formulation, the results have been disappointing. The drug showed safety and tolerability but may not meet its primary efficacy goal, casting doubt on the future of the program.
In response to the setback, First Wave intends to meet with the FDA to discuss the data obtained from adrulipase studies and determine the requirements for a potential Phase II study to support regulatory approval. However, this news caused a significant decline in the company’s stock.
Currently, pancreatic insufficiency in cystic fibrosis patients is typically managed with pig-derived pancreatic enzyme replacement therapy (PERT) products like Creon from AbbVie and Zenpep from Nestle Health Science. These products help patients by providing the necessary pancreatic enzymes to break down food and improve nutrient absorption, reducing symptoms such as bloating, cramps, diarrhea, and weight loss.
First Wave’s adrulipase, a recombinant form of pancreatic lipase produced in yeast cells, offers an animal-free alternative to porcine-based PERT. Porcine PERT can be challenging to manufacture and may face shortages due to factors like swine flu. Furthermore, some patients have ethical concerns about using products derived from animals.
One potential advantage of adrulipase is its ability to reduce the number of daily capsules required compared to porcine PERT, which can be quite high due to the lower activity of lipases in humans’ acidic environment. The initial formulation of adrulipase was found to be less effective than porcine PERT in enhancing fat digestion in the gastrointestinal tract, while a subsequent study suggested some benefits in combining the two therapies.
To address these issues, First Wave incorporated acid-resistant granules in capsules, a technology already used in Creon and Zenpep, to protect adrulipase in the stomach and enhance its release in the small intestine.
“Preliminary data from the Phase II SPAN clinical trial indicate our enhanced microgranule delivery formulation of adrulipase was safe and well tolerated. We are in the process of analyzing the dataset and anticipate having a topline review of the primary and secondary endpoints in the September timeframe.” Mr. Sapirstein added: “We would like to thank the patients who volunteered to participate in the study and the investigators and their staff at our three participating clinical trial sites for ensuring that the trial was fully enrolled and completed on time.”
– James Sapirstein, President and CEO of First Wave BioPharma
Aside from adrulipase, First Wave’s only other clinical-stage drug candidate is niclosamide, which they are repurposing for inflammatory bowel disease. Currently, it is in a Phase IIa trial for ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS).
