Allena Pharmaceuticals Inc.'s phase III URIROX-1 trial of reloxaliase hit its primary endpoint, with a statistically significant reduction in urinary oxalate (Uox) in patients with enteric hyperoxaluria (EH), while its phase II Study 206 trial showed reduced plasma oxalate reduction in patients with EH and advanced chronic kidney disease (CKD). Yet the market saw Allena's shares (NASDAQ:ALNA) drop dramatically Thursday, closing down 61.7% at $2.24 per share.

Louis Brenner, president and CEO, Allena

"We don't comment on trading volumes," said Louis Brenner, Allena's president and CEO, told BioWorld. "Our job is to focus on development of the program."

Brenner, a nephrologist, said kidney disease has an underserved population, and R&D in general is underinvested.

"Much has failed. We have positive data," he added.

The company is pursuing an accelerated approval regulatory strategy and, for Study 206, it is considering a registrational path for reloxaliase to treat patients with EH and advanced CKD.

"The data gives us a heightened sense of conviction," Brenner said. "We as company take it seriously. We do have an agreed-upon path toward accelerated approval and are progressing along that path. We will await more complete data from studies to determine if we need to make modifications for the path we're on."

People with enteric hyperoxaluria, a subset of secondary hyperoxaluria sufferers that Allena has estimated totals about 200,000 to 250,000 in the U.S., have an increased risk of kidney stones and kidney damage attributable to excess absorption of oxalate from the gastrointestinal (GI) tract. It's associated with bariatric surgery, Crohn's disease, ulcerative colitis, short bowel syndrome, chronic pancreatic insufficiency and cholestatic liver disease – all underlying enteric conditions that can dispose individuals to having high oxalate levels. In both Allena's studies, treatment led to reductions in measures of oxalate burden.

"The condition is not well-appreciated," Brenner said. "We have to convince people of the merits. We're getting solid feedback from the subscriber community."

A near miss in a URIROX-1 secondary endpoint could be the culprit that tripped up the market. The lead secondary endpoint evaluated the proportion of patients on reloxaliase with a ≥20% reduction from baseline in 24-hour (UOx) excretion during weeks one through four. Across all subjects, the proportion of patients treated with reloxaliase who achieved a ≥20% reduction from baseline in 24-hour UOx excretion was 48.3%, compared to 31.6% for patients on placebo (p=0.06).

However, the multicenter, global, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of reloxaliase in 115 patients in a four-week treatment period hit its primary endpoint. A mean reduction of 22.6% in average 24-hour UOx excretion was measured during weeks one through four among patients treated with reloxaliase, compared to a 9.7% reduction in the placebo group (least square [LS] mean treatment difference of -14.3%, p=0.004). Also, in a secondary endpoint, the stratified analysis of the primary endpoint in bariatric surgery patients (68% of the subjects), those treated with reloxaliase achieved a mean reduction of 21.2% in average 24-hour UOx excretion, compared to 6% for patients treated with placebo (LS mean difference of -16.2%, p=0.01).

The phase II, a multicenter, open-label, single-arm study designed to enroll between 15 and 20 patients in the U.S. and Europe ages 12 and older, is to evaluate reloxaliase in high-risk patients with EH and advanced CKD. The primary endpoints were change from baseline in 24-hour UOx excretion and POx levels. Two patients with CKD stage 3 had substantial reduction in 24-hour UOx excretion over weeks four to 12 (29% and 42%). They also showed a substantial reduction in POx (42% and 16%). Six patients with CKD stage 5, including five patients on dialysis, demonstrated substantial reductions in POx levels over weeks four to 12 (ranging from 19% to 68%).

Other companies working on hyperoxaluria therapies include Dicerna Pharmaceuticals Inc. and Alnylam Pharmaceuticals Inc., both of which are advancing RNAi-based candidates for the treatment of primary hyperoxaluria, and Oxthera AB (formerly Ixion Biotechnology), with an oral lyophilized capsule containing live intestinal bacteria, Oxalobacter formigenes (strain HC-1), also for primary hyperoxaluria.

Allena, launched in 2011, was created by former executives and investors of Alnara Pharmaceuticals Inc. (See BioWorld, Nov. 16, 2011.)

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