Potassium bicarbonate + potassium citrate

Unassigned

New Medicines

Distal renal tubular acidosis (dRTA)

Information

New formulation
Advicenne
Advicenne

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Phase III Clinical Trials
Yes

Mar 19: MAA submitted to the European Medicines Agency for ADV7103, as a treatment for distal renal tubular acidosis (dRTA) [4].


Jul 18: Advicenne is planning to file ADV7103 for market authorization for dRTA in Europe in H2 2018 and anticipates its commercial launch in 2020 in Europe. A PII/III clinical trial assessing ADV7103 in dRTA patients in the US is expected to start in H2 18. Commercial launch in the US is anticipated in 2021 [3].


Jul 17: Granted orphan drug status in EU [2].

Category

Fixed dose combination of potassium bicarbonate and potassium citrate, in the form of prolonged-release coated granule (micro-tablets) for a 12-hour absorption.
dRTA is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis. The classic form is often associated with hypokalemia whereas other forms of acquired dRTA may be associated with hypokalemia, hyperkalemia or normokalemia. All forms of dRTA are chronic and may have significant effects on growth and development, but renal failure is uncommon. Prevalence of dRTA is unknown but is often underreported [1].
Distal renal tubular acidosis (dRTA)
Oral

Trial or other data

Sep 18: Advicenne reports that the US FDA cleared its Investigational New Drug application for the pivotal PIII ARENA-2 trial in the US. It will investigate the safety and efficacy of the product in preventing the development of metabolic acidosis defined by serum bicarbonate level in 40 paediatric (aged 6 months to < 18 years) and adult (aged 18 to 65 years) patients with primary dRTA [2].


Jul 18: Advicenne reports 24 month data from B22CS trial. 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 [3].


Nov 17: Positive 6 months follow-up data from the B22CS trial reported. The product´s efficacy, was shown to be maintained at 6 months in this open label extension study, with blood bicarbonate levels above 21 mM - the normal level - in 79% of the patients. Individual ADV7103 doses ranged from 1.3 to 7.2 mEq/kg/day. Overall, patients and/or their parents were extremely satisfied with ADV7103. This was measured using a visual analogue scale (VAS) questionnaire quoting from 0 (no improvement at all) to 100% (extremely important improvement). The change of treatment from standard of care to ADV7103 allowed an average improvement of the patients´ quality of life of 80.5%; depending on the age group considered the improvement ranged from 76 to 98% [3].


Sep 17: Positive results reported for an open-label extension PIII trial evaluating safety, tolerability and long-term efficacy of fixed dose combination of potassium bicarbonate and potassium citrate in 24 patients with distal renal tubular acidosis (B22CS; EudraCT2013-003828-36). Normal blood bicarbonate levels were attained in most patients treated with doses of ADV7103 ranging from 0.75 to 8.45 mEq/kg/day. Mean doses of 1.7, 2.3, 3.8 and 6.1 mEq/kg/day ADV7103 were given, respectively, in adults, adolescents, children, and infants. Non-inferiority of ADV7103 vs. SoC or baseline literature data was consistently demonstrated (per protocol, intention-to-treat, as well as sensitivity analyses). Kalaemia was normalised with ADV7103 with only two doses per day. These analyses were able to show that ADV7103 is superior to the SoC (p<0.0047) [3].


Sep 17: PII/III trial (B21CS; EudraCT2013-002988-25) has met its primary as well as secondary endpoints, by restoring biological parameters associated with the disease [2].


May 16: PII/III trial that evaluated the efficacy, safety, tolerability and acceptability of fixed dose combination of potassium bicarbonate and potassium citrate vs. standard of care, in patients aged 1 month to 64 years with distal renal tubular acidosis completes (B21CS; EudraCT2013-002988-25). The open-label, non-inferiority sequential study enrolled 32 patients in Slovakia [2].