Allena Pharmaceuticals Announces Interim Study Results

Allena Pharmaceuticals, Inc. recently announced interim data from Study 206, its Phase 2 basket clinical trial of reloxaliase, an orally administered, recombinant oxalate-degrading enzyme. Study 206 includes adult and pediatric patients suffering from the progression of primary hyperoxaluria (PH) or enteric hyperoxaluria (EH) with advanced chronic kidney disease (CKD), both of which can lead to systemic oxalosis, a potentially life-threating condition. Consistent with Allena’s prior clinical experience, EH patients treated with reloxaliase in Study 206 demonstrated a substantial treatment effect. This includes EH patients with advanced CKD, a patient population not previously treated with reloxaliase, who showed reductions in urine oxalate (UOx) and plasma oxalate (POx).

“We are pleased to see a robust response to reloxaliase in EH patients suffering from advanced stages of the disease. We believe this reflects reloxaliase’s activity and novel mechanism of action of degrading oxalate within the GI tract, which is well-targeted to treat excess oxalate absorption driven by an underlying GI disorder. The potential to alleviate the high oxalate burden on these patients is very encouraging,” said Louis Brenner, MD, President and Chief Executive Officer of Allena Pharmaceuticals. “To our knowledge, this is a first demonstration of a specific pharmacologic therapy leading to reduction in plasma oxalate and urinary oxalate levels in patients with EH and decreased kidney function, which represents a significant advancement for the field and especially for patients with systemic oxalosis. These results advance our efforts to develop reloxaliase as a potential first-in-class therapy for patients with enteric hyperoxaluria, and we look forward to additional data from Study 206, as well as topline data from our pivotal Phase 3 URIROX-1 trial, anticipated in the second half of the year.”

Study 206 is a multi-center, open-label, single-arm Phase 2 clinical trial designed to enroll between 15 and 20 patients in the US and Europe aged 12 and older. Patients orally administer 7,500 units of reloxaliase with each meal or snack five times a day, for 12 consecutive weeks. The primary endpoints of the trial are change from baseline in 24-hour UOx excretion and POx levels. UOx was collected for patients who are not on dialysis.

The first seven patients have completed treatment, including one EH patient with advanced CKD, one EH patient with a functioning kidney transplant, and two patients with EH who are on dialysis. Three patients had PH and preserved renal function.

-All four patients with EH experienced a reduction in POx, with an average reduction of 40% compared to baseline (range 23% to 49%). The two patients not on dialysis also experienced reductions in UOx of 29% and 42%, respectively. The treatment effect observed in these EH patients supports a continued focus on treating EH patients with CKD, kidney transplantation or dialysis dependence in an effort to reduce further oxalate damage.

-Three patients with PH type 2 or PH type 3 with preserved renal function were treated. These are the first patients with any form of PH treated with reloxaliase. One patient had a >20% mean reduction in UOx excretion, while the other two patients did not show a response to reloxaliase. Allena intends to narrow its further evaluation of reloxaliase in PH to patients with compromised renal function where the GI mechanism of action may play a more important role.

-This trial encompasses the longest reloxaliase treatment duration thus far. All patient populations are being treated for 3 months with more frequent dosing of reloxaliase than the company’s prior Phase 2 studies (7,500 units of reloxaliase, five times per day). Average patient dosing compliance was greater than 90%. Treatment with reloxaliase was well-tolerated in all patient populations, with no reported treatment-related serious adverse events.

“I am extremely encouraged by the interim data from Study 206. People living with EH and significant renal compromise suffer from underlying GI conditions, which perpetuate a vicious and potentially fatal cycle of kidney damage, transplantation and return to dialysis, and there are no approved therapies available with which to treat them,” said Felix Knauf, Professor of Nephrology, Charite’ University Hospital Berlin, Germany and Assistant Professor Adjunct at Yale University. “Though early, these results suggest that reloxaliase may offer a well-tolerated and easily administered new medicine for these patients. By reducing both UOx and POx levels, reloxaliase has the potential to improve renal outcomes by lessening the likelihood that patients will develop calcium oxalate crystal deposition in their kidneys or other organs. I am eager to work with Allena to enroll additional patients in this study, as we continue to evaluate potential near- and long-term clinical benefits of reloxaliase treatment.”

Hyperoxaluria is a metabolic disorder characterized by elevated urinary oxalate levels that may be due to either overproduction of oxalate by the liver from a genetic defect, known as primary hyperoxaluria, or from the excess absorption of oxalate from the diet, known as secondary hyperoxaluria. Secondary hyperoxaluria is further characterized either as enteric, resulting from a chronic and unremediable underlying GI disorder, or idiopathic, meaning the underlying cause is unknown. Systemic oxalosis occurs when excess oxalate is present throughout the body including the blood, kidney, bones, joints, eyes and heart. People living with systemic oxalosis have varying degrees of renal impairment including kidney stones, nephrocalcinosis, chronic kidney disease, and end-stage renal disease.

Reloxaliase is an orally administered, recombinant oxalate-degrading enzyme that is being developed for the treatment of severe hyperoxaluria. Reloxaliase targets oxalate in the GI tract in an effort to reduce the burden of both dietary and endogenously produced oxalate. Reloxaliase has the potential to decrease the oxalate available systemically for deposition as calcium oxalate crystals or stones in the kidneys, as well as reduce long-term kidney complications. Reloxaliase is being evaluated in the ongoing pivotal Phase 3 URIROX-1 and URIROX-2 trials for patients with enteric hyperoxaluria and the ongoing Phase 2 basket trial for adult and pediatric patients suffering from primary hyperoxaluria or enteric hyperoxaluria with advanced chronic kidney disease. In addition, reloxaliase has been granted separate orphan drug designations by the US FDA for the treatment of primary hyperoxaluria and for the treatment of pediatric hyperoxaluria. The European Commission has granted orphan drug designation for reloxaliase for the treatment of primary hyperoxaluria.

Allena Pharmaceuticals, Inc. is a late-stage biopharmaceutical company dedicated to developing and commercializing first-in-class, oral enzyme therapeutics to treat patients with rare and severe metabolic and kidney disorders. Allena’s lead product candidate, reloxaliase, is a first-in-class, oral enzyme therapeutic for the treatment of hyperoxaluria, a metabolic disorder characterized by markedly elevated urinary oxalate levels and commonly associated with kidney stones, chronic kidney disease, and other serious kidney disorders.