First Wave BioPharma Announces Initiation of Phase 2 Trial Investigating Enhanced Adrulipase Formulation in Exocrine Pancreatic Insufficiency in Patients With Cystic Fibrosis

First Wave BioPharma, Inc. recently announced it will initiate its planned Phase 2 clinical trial of an enhanced enteric microgranule delivery formulation for adrulipase for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF). The US FDA has reviewed the Investigational New Drug (IND) amendment and after requesting and receiving a modified protocol, has not provided any further comments in the 60-day period of review.

The Phase 2 multi-center study is designed to investigate the safety, tolerability, and efficacy of an enteric microgranule delivery formulation for adrulipase in a titrated dose-escalation study involving an estimated 12 patients. The primary efficacy endpoint is the coefficient of fat absorption (CFA), with secondary endpoints of stool weight, signs, and symptoms of malabsorption and coefficient of nitrogen absorption (CNA).

First Wave BioPharma expects to initiate patient screening in early February 2023, with topline data anticipated by mid-2023. Three clinical trial sites in the US will be participating in the trial.

“We are very pleased to announce the initiation of the Phase 2 clinical trial investigating our new formulation of adrulipase as a potential treatment for EPI associated with cystic fibrosis and chronic pancreatitis,” said James Sapirstein, President and CEO of First Wave BioPharma. “Preclinical research has demonstrated the new adrulipase formulation is able to deliver the drug in the intended area of the gastrointestinal tract where it can provide the desired therapeutic effect. This Phase 2 clinical trial is designed to test that capability as a key step in our goal to provide patients with a more effective and convenient therapeutic option for EPI associated with cystic fibrosis and chronic pancreatitis.”

In vitro data suggest the microgranule drug delivery formulation offers improved protection against the acidic pH in the stomach followed by the rapid release of adrulipase in the small intestine where the drug is expected to mix with food and deliver its therapeutic benefit. Additionally, in vitro research indicates the enhanced formulation has the potential to significantly decrease the number of pills a patient would need to take to achieve the desired therapeutic effect. The pill burden for current commercial porcine pancreatic enzyme replacement therapy (PERT) can be as high as 40 capsules per day, creating a substantial challenge for EPI patients.

The Phase 2 SPAN trial is designed to investigate the safety, tolerability and efficacy of a new enteric microgranule formulation of adrulipase. The SPAN trial is an open-label study that will be conducted at three sites in the US. A total of 12 cystic fibrosis patients, 18 years or older are expected to be enrolled. The trial design employs a dose titration strategy. Patients will be screened at baseline to ensure that they have a coefficient of fat absorption (CFA) of at least 80%. Eligible patients will then be switched from their commercial enzyme product to adrulipase. Each patient will be started on a low dose of adrulipase. If the patient is not clinically controlled, the patient will be switched to a medium dose, and if not controlled on this dose, the patient will be advanced to a high dose. The titrations will be carried out over a 3-week period, after which a CFA will be obtained. End of study CFAs will be compared to the baseline CFAs in a descriptive fashion. A post-treatment safety visit will be conducted one week after completing the treatment period.

Adrulipase is a recombinant lipase enzyme administered as an oral, non-systemic biologic capsule for the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) and chronic pancreatitis (CP). Adrulipase is derived from the Yarrowia lipolytica yeast lipase and is designed to break up fat molecules in the digestive tract of EPI patients so that they can be absorbed as nutrients. EPI is a condition characterized by deficiency of the exocrine pancreatic enzymes, resulting in a patient’s inability to digest food properly, or maldigestion. The deficiency in this enzyme can be responsible for greasy diarrhea, fecal urge and weight loss. There are more than 30,000 patients in the US with EPI caused by cystic fibrosis according to the Cystic Fibrosis Foundation and approximately 90,000 patients in the US with EPI caused by chronic pancreatitis according to the National Pancreas Foundation.

First Wave BioPharma is a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases. The company is currently advancing a therapeutic development pipeline with multiple clinical stage programs built around its two proprietary technologies – the biologic adrulipase, a recombinant lipase enzyme designed to enable the digestion of fats and other nutrients, and niclosamide, an oral small molecule with anti-inflammatory properties. First Wave is advancing two Phase 2 clinical programs built around adrulipase for the treatment of exocrine pancreatic insufficiency (FW-EPI) in patients with cystic fibrosis (CF) and chronic pancreatitis (CP). In developing adrulipase, First Wave is seeking to provide CF and CP patients with a safe and effective therapy to control EPI that is non-animal derived and offers the potential to dramatically reduce their daily pill burden. The company is also advancing multiple programs involving niclosamide, including FW-UP for ulcerative proctitis and ulcerative proctosigmoiditis, FW-UC for ulcerative colitis, and FW-CD for Crohn’s disease. First Wave BioPharma is headquartered in Boca Raton, FL. For more information, visit www.firstwavebio.com.