Anthera Pharmaceuticals has acknowledged that its late-stage candidate Sollpura™ (liprotamase) failed a Phase III clinical trial in cystic fibrosis patients with exocrine pancreatic insufficiency (EPI).
Sollpura narrowly missed a primary endpoint of the Solution clinical trial, change in the coefficient of fat absorption (CFA) noninferiority margin, Anthera said yesterday. However, the candidate met the noninferiority criterion in analyses of CFA in two-patient subgroups: modified intent-to-treat baseline observation carried forward and per protocol.
The company blamed its endpoint miss on time restrictions and amounts allowed per protocol, hindering some patients' ability to increase their doses during the study, as well as on other patients being prevented from increasing their dose due to the daily 10,000 lipase units/kg per day limit for porcine pancreatic enzyme replacement therapies.
In addition, according to Anthera, Sollpura may have been underdosed versus the dose of the drug to which it was being compared, the Janssen-marketed treatment Pancreaze® (pancrelipase), indicated for exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.
Anthera said Sollpura was generally well tolerated compared to Pancreaze, while acknowledging that symptoms related to malabsorption were generally modestly more frequent in the Sollpura arm.
The Solution study also confirmed that the ratio of Sollpura’s three enzymes showed an appropriate response in the coefficient of nitrogen absorption (CNA), Anthera added.
The company said it plans to launch an additional clinical study of Sollpura in patients with EPI due to cystic fibrosis, with the goal of enabling optimized dosing and dose titration by allowing investigators and patients to adjust their Sollpura dose based upon malabsorption symptoms during the study.
The new study will begin in the first quarter of 2017 and will necessitate a delay of a planned BLA filing for Sollpura to “around Q1 2018,” Anthera said.
News of the trial failure sparked an investor sell-off that sent the price of Anthera shares plummeting in premarket trading by 63% as of 9:07 a.m., to $2.01.
The failure is the second reported by Anthera in recent weeks. Last month, the company acknowledged that its systemic lupus erythematosus candidate Blisibimod missed the primary endpoint in the Phase III CHABLIS-SC1 trial by achieving a statistically insignificant difference in achieving the study’s primary endpoint of improvement after 52 weeks of treatment based on the SLE Responder Index-6 (SRI-6), although on December 6, Anthera said the candidate showed positive trends in a week-48 analysis in the Phase II BRIGHT-SC study in 57 patients with immunoglobulin A (IgA) nephropathy.