distal Renal Tubular Acidosis (dRTA) – A Renal Orphan Disease

ADV7103 is an investigational drug, designed to address dRTA, both in children and adults. dRTA can have a genetic origin that mainly affects children or an acquired origin for adults who may have acquired the condition as a result of autoimmune disease.

dRTA is characterized by impaired ability of the kidney to excrete protons (acids) into the urine with consequent imbalance of blood pH leading to severe and long-term complications. These include kidney damage (nephrocalcinosis, lithiasis), growth retardation and rickets (a disease affecting bone development) in children, a series of metabolic disorders (hypokalemia, hypercalcemia, hypercalciuria) and impairment of renal function.

There are no approved treatments for dRTA.

  Designed for a twice-a-day treatment

  Designed for a twice-a-day treatment

ADV7103 is an innovative product with a prolonged-release formulation, designed to be specifically appropriate for children and adults and to maintain a sustained-release over a 12-hour period for twice-a-day treatment. ADV7103 was developed as a multi-particulate formulation in 2mm granules that contains two active pharmaceutical ingredients. ADV7103 is tasteless and easy to administer orally in patients of all ages.

In Europe, ADV7103 has shown positive results in a pivotal Phase III Study in children and adults with dRTA (ARENA-1). The objective of ARENA-1 was to evaluate the efficacy, safety and acceptability of ADV7103.

The Phase III study was shown to remove the main biological defects observed with the disease, achieving primary and secondary objectives.

Normal blood bicarbonate levels were attained in most patients treated with doses of ADV7103 ranging from 0.75 to 8.45 mEq/kg/day. Non-inferiority of ADV7103 relative to SoC or baseline literature data was consistently demonstrated (per protocol, intention-to-treat, as well as sensitivity analyses). Kalemia was normalized with ADV7103 with only two doses per day.

Preliminary results of the Phase III Extension Study, an open-label clinical study, confirm the efficacy and safety of ADV7103 after 24 months of treatment. Results from 90% of patients at 6 months, 12 months, 18 months and 24 months demonstrate the ability of ADV7103 to normalize biological disorders caused by dRTA throughout the course of treatment. This efficacy, measured by blood bicarbonate levels and stabilized serum potassium, remains constant in about 80% of patients.

The safety profile of ADV7103 remains very favorable during the treatment, with only 15% of patients having reported digestive side effects considered as product-related, rated as mild for three patients and as medium for one patient.

ADV7103 was granted Orphan Drug Designation by the EU for the treatment of dRTA in June 2017.

In the United States, the U.S. Food and Drug Administration (FDA) has cleared ADV7103’s Investigational New Drug (IND) application, allowing the initiation of the ARENA-2 pivotal Phase III trial for the treatment of distal Renal Tubular Acidosis (dRTA) in the United States.

ARENA-2 is a pivotal Phase III, prospective, multicenter, randomized, double-blinded, placebo-controlled study expected to enroll approximately 40 patients in the United States. The primary objective of the study is to evaluate the safety and efficacy of ADV7103 versus placebo in preventing the development of metabolic acidosis defined by serum bicarbonate level in pediatric (6 months to < 18 years of age) and adult (18 to 65 years of age) subjects with primary dRTA.

ARENA-2 has also received a No Objection Letter from Health Canada’s Office of Clinical Trials to extend the Phase III trial in Canada.

ADV7103 is an investigational drug and has not yet been approved by any regulatory authority.

  Cystinuria

ADV7103 is also being developed for the treatment of a second indication, cystinuria, an inherited renal tubulopathy.

ADV7103 has received authorization from the French National Agency of Medicine and Health Products Safety (ANSM) and from the Belgian Health Authority (FAMHP) to initiate a pivotal Phase II/III clinical trial in cystinuria (CORAL study).

The CORAL trial has been designed to evaluate the efficacy, safety, tolerance and compliance of ADV7103 in patients living with cystinuria.

Since its founding in 2007, Advicenne has been dedicated to developing and commercializing innovative treatments that address unmet medical needs in the area of nephrology. Our lead drug candidate, ADV7103, is in late-stage clinical trials for two indications: distal renal tubular acidosis (dRTA) and cystinuria. Listed on both the Euronext Paris and Euronext Brussels stock exchanges, the company is headquartered in Nîmes, France.

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