Date: 2016-12-27
Type of information: Results
phase: 3
Announcement: results
Company: Anthera Pharmaceuticals (USA - CA)
Product: Sollpura® (liprotamase)
Action
mechanism: enzyme replacement therapy. Sollpura® is a novel, non-porcine PERT containing a proprietary, biotechnology-derived formulation of cross-linked crystalline lipase, crystalline protease, and amorphous amylase with broad substrate specificity, that has been designed for purity (no potential for viral contamination), precise dose standardization, resistance against proteolysis without polymeric coating, and stability in acid pH for reliable potency of activity in the proximal small intestine.
Disease: cystic fibrosis patients with exocrine pancreatic insufficiency
Therapeutic area: Rare diseases - Genetic diseases
Country: Canada, Czech Republic, Hungary, Israel, Poland, Spain, USA
Trial
details: The Phase 3 SOLUTION clinical study is a multicenter, randomized, open-label, assessor-blind, non-inferiority, active-comparator study designed to evaluate the efficacy and safety of Sollpura in people with EPI due to cystic fibrosis. This pivotal study is intended to evaluate the non-inferiority of Sollpura compared with a commercially available PERT in a population enriched for PERT responders. The primary efficacy endpoint of this study will be comparative efficacy measured as the change in the coefficient of fat absorption (CFA) at the end of therapy. (NCT02279498)
Latest
news: * On December 27, 2016, Anthera Pharmaceuticals announced the top line results of the SOLUTION clinical study in cystic fibrosis patients with exocrine pancreatic insufficiency (EPI). The study narrowly missed the CFA non-inferiority margin of the primary modified Intent to Treat (mITT) analysis; however, by additional pre-specified analyses of CFA (mITT-Baseline Observation Carried Forward and Per Protocol), Sollpura® (liprotamase) met the non-inferiority criterion. The study also confirmed that the ratio of the three enzymes in Sollpura demonstrated an appropriate response in the coefficient of nitrogen absorption (CNA). CNA is a measure of protein digestion and absorption and is a key requirement of Anthera's planned US FDA regulatory submission. Anthera expects to release data from the extension phase of the study in Q1 2017. * On August 16, 2016, Anthera Pharmaceuticals announced that the Data and Safety Monitoring Board (DSMB) completed its first pre-planned safety review of the Phase 3 SOLUTION clinical study of Sollpura® in cystic fibrosis patients with exocrine pancreatic insufficiency. The DSMB had "no concerns regarding safety of the data to date, and voted that the study continue without modification to the protocol or charter." * On June 28, 2016, Anthera Pharmaceuticals announced that the company has closed patient screening for Phase 3 SOLUTION clinical study evaluating the efficacy and safety of Sollpura® (liprotamase), a conventional biotechnological pancreatic enzyme replacement therapy (PERT), compared to an approved, porcine-derived, enteric-coated product for the treatment of exocrine pancreatic insufficiency (EPI). The Company expects top-line efficacy data to be presented in the fourth quarter of 2016 and is anticipated to support marketing approval for Sollpura® as a treatment for EPI. * On October 2, 2015, Anthera Pharmaceuticals announced the initiation of the SOLUTION (Study of Oral Liprotamase Unit-Matched Therapy Of Non-Porcine Origin in People With Cystic Fibrosis) Phase 3 clinical study evaluating the efficacy and safety of Sollpura® (liprotamase), a microbial derived, biotech pancreatic enzyme replacement therapy (PERT), compared to an approved, porcine-derived, enteric-coated product for the treatment of exocrine pancreatic insufficiency (EPI). Results from the SOLUTION clinical study are anticipated to support marketing approval for Sollpura® as a treatment for exocrine pancreatic insufficiency.
In analyzing the results of the SOLUTION study, patients' ability to increase their doses during the study were hindered by time restrictions and amounts allowed per protocol, while other patients were prevented from increasing their dose due to the daily limit (10,000 lipase units/kg/day) for porcine pancreatic enzyme replacement therapies (PERTs). Sollpura was generally well tolerated compared to Pancreaze, although symptoms related to malabsorption were generally modestly more frequent in the Sollpura arm.
In addition to the challenges to dose escalation inherent in the design of the SOLUTION study, analytical techniques for measuring the activity of lipase enzymes based on duodenal pH of Cystic Fibrosis patients, indicate that Sollpura may have been under dosed versus the Pancreaze labeled dose.
Given the robust activity of Sollpura in this study, in the context of dose titration limitation and apparent reduced dosage activity, Anthera will initiate activities for an additional clinical study of Sollpura in patients with EPI due to cystic fibrosis, which Anthera expects will enable optimized dosing and dose titration. This study will provide investigators and patients the flexibility to adjust their Sollpura dose based upon malabsorption symptoms at any time during the study. Anthera believes that these modifications in the study design will allow patients to achieve the optimal level of fat absorption as measured by CFA. The new study will begin in 1Q'17, and Anthera anticipates only a modest delay in the filing of the BLA around Q1 2018, as the new study will complete concurrently with the completion of required CMC activities.
