The first patients have been treated in a phase 2 trial evaluating Allena Pharmaceuticals, Inc.’s ALLN-177 in adults and adolescents with primary hyperoxaluria or enteric hyperoxaluria with advanced chronic kidney disease (CKD) and elevated plasma oxalate.
A first-in-class, non-absorbed, orally-administered enzyme, ALLN-177 is optimized to degrade oxalate within the gastrointestinal (GI) tract to treat severe hyperoxaluria, a metabolic disorder characterized by elevated urinary oxalate levels.
In an exclusive interview with Rare Disease Report®
, Felix Knauf, MD, a nephrologist from Charité at University Medicine Berlin who advised Allena on the study design for the trial, (Study 206), and who will be 1 of the European investigators, described the significance of the drug’s potential for patients with primary hyperoxaluria or enteric hyperoxaluria with advanced CKD.
“Usually, the affected patients have chronic disease that lasts over many years and gets worse over time with regards to the complications and the severity of the disease. Therefore, the new drug has the hopes of particularly helping these chronically affected patients to find a treatment that will prevent the complications [of the disease],” he said.
Dr. Knauf went on to explain that once patients end up on dialysis and the need for a kidney transplantation arises, patients’ quality of life decreases and mortality increases. In addition, if kidney transplantation becomes the only treatment option, it is dependent on organ donor availability, which can be unpredictable in supply. With ALLN-177 though, patients may potentially avoid losing more, significant amounts of their kidney function or delay dialysis or kidney transplantation.
As a multi-center, open-label, single arm trial, Study 206
will enroll between 15 and 20 patients aged 12 and older in both the United States and Europe. Clinical trials in the United States have already started enrollment while investigators in Europe are preparing to enroll patients at European sites in the third quarter of 2018. Enrolled participants will self-administer 7500 units of ALLN-177 with each meal or snack 5 times per day. The change from baseline in 24-hour urinary oxalate excretion and plasma oxalate levels will serve as the primary endpoints. Patients with kidney failure or who are on dialysis may comprise up to 25% of total enrollment.
“The first trial would not address whether these patients reach dialysis earlier or whether kidney transplantation is not needed,” added Dr. Knauf. “This first trial will solely show whether we are able to reduce plasma oxalate as a marker for reducing oxalate concentration. We believe this most likely will translate into other outcomes, and this, of course, will need to be shown in subsequent trials, but this very first trial is a proof of concept regarding whether the drug is capable of reducing oxalate as the agent that does the harm.”
ALLN-177 previously received an orphan drug designation
in July 2017 for the treatment of primary hyperoxaluria and pediatric hyperoxaluria. The European Commission has also granted an orphan drug designation to ALLN-177 for the treatment of primary hyperoxaluria.
In addition, ALLN-177 is being evaluated in URIROX-1, an ongoing phase 3 clinical trial in patients with enteric hyperoxaluria who have normal kidney function or mild to moderate CKD.