Gut punch: First Wave's challenger to AbbVie fails phase 2 again

First Wave BioPharma’s bid to challenge AbbVie for a gastrointestinal market has suffered a setback, with the biotech telling investors “it is likely the primary efficacy endpoint was not achieved.” 

Florida-based First Wave is developing a formulation of adrulipase, a yeast-based alternative to AbbVie’s Creon and other pig-derived pancreatic enzyme replacement therapies. The therapies are used to treat nutritional deficiencies related to conditions including cystic fibrosis. First Wave bet its enzyme is a safer option with a lower pill burden and simplified sourcing that eliminates the risk of pathogen transmission. 

The biotech kicked off a small clinical trial to test its candidate earlier this year. Subjects stopped taking pig-derived enzyme replacement therapies and switched to adrulipase. After three weeks, First Wave tracked the change in coefficient of fat absorption (CFA) from baseline.

CFA is the percentage of absorbed fat in the diet. Normally, CFA is around 90%, but the figure can sink to below 40% in untreated cystic fibrosis patients. Existing therapies move CFA up toward normal—people taking Creon for five to six days have a CFA of 89%—and set the bar for adrulipase.  

The phase 2 trial data suggest the candidate may fall short of that bar. First Wave is yet to share numbers from the study but said the “preliminary data … indicate that it is likely the primary efficacy endpoint was not achieved.” The primary efficacy endpoint compared the CFA for adrulipase to baseline figures for commercial pancreatic enzyme replacement therapies “using descriptive methods.” 

First Wave’s share price fell 19% to $1.05 in the wake of the update, but the biotech, which has a market cap of around $5 million, is undeterred. Management plans to meet with the FDA in the fourth quarter to “discuss the parameters for a registrational phase 3 clinical trial.”

The latest setback comes two years after a phase 2 clinical trial of an earlier formulation of adrulipase missed its primary efficacy endpoint. First Wave pinned the blame for that failure on the enteric capsule formulation, leading the biotech to create a microgranule version and advance it into the phase 2 study that read out Thursday.