potassium bicarbonate/potassium citrate (ADV7103) / Advicenne - LARVOL DELTA

TWICE ADMINISTRATED NEW ALKALINIZING AGENT (ADV7103) IN PATIENTS WITH CYSTINURIA (ESPN 2025) - "In pediatric patients with cystinuria, the new prolonged-release formulation of potassium citrate and potassium bicarbonate could be a safe and effective treatment option for achieving stable urinary alkalinization. This formulation was well-tolerated and enhanced daily life and patient adherence."

Clinical • Genetic Disorders • Nephrology • Pediatrics • Renal Calculi

Cystinuria in children: diagnosis and treatment. (PubMed, World J Urol) - "Cystinuria is the primary hereditary factor contributing to the formation of kidney stones throughout childhood. It is a genetic disorder that typically manifests as recurrent stone formations. The aim of the treatment of genetically caused pediatric stone diseases is to prevent stone formation with medical treatments, remove existing stones through surgical treatments, and mitigate the risk of developing chronic kidney disease in the future."

Journal • Review • Chronic Kidney Disease • Genetic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease • Urolithiasis

Long-term clinical outcomes of dRTA patients treated with Sibnayal®, an oral twice-daily fixed and prolonged-release combination of potassium bicarbonate and potassium citrate (IPNA 2025) - "There is a significant improvement of mean lumbar BMD Z-score between baseline and EoF in pre- and post-pubertal patients (respectively, p=0.035 and p=0.0007) whilst it was maintained in patients in pubertal phase (p=NS). Conclusions Long-term data support the good safety and efficacy profile of Sibnayal® in the treatment of dRTA with adequate control of metabolic acidosis, stable kidney function and significant positive long-term outcomes, notably on growth, lumbar spine BMD and bone metabolism in patients with dRTA treated over 6 years in average."

Clinical • Clinical data • Chronic Kidney Disease • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Rare Diseases • Renal Calculi • ATP6V0A4

SUCCESSFUL TREATMENT OF DISTAL RENAL TUBULAR ACIDOSIS WITH EXTENDED-RELEASE ORAL ALKALINE SALTS IN AN ADULT PATIENT (ISN-WCN 2025) - "Due to the gastrointestinal side effects, 50 mg spironolactone daily was added to therapy to maintain serum potassium levels at the lower normal limit. Conclusions In our case of an adult with dRTA, the combination of extended-release potassium citrate and potassium bicarbonate was shown to significantly improve metabolic acidosis and maintain potassium levels in the normal range with only two doses per day and with excellent gastrointestinal tolerability compared to standard treatments. We believe that this innovative formulation may improve compliance with long-term treatment and reduce nephrocalcinosis and nephrolithiasis as well as the consequences of hypokalemia."

Clinical • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Osteoporosis • Pain • Renal Calculi • Rheumatology

Recent Developments in the Treatment of Pediatric Distal Renal Tubular Acidosis. (PubMed, Paediatr Drugs) - "A novel investigational drug, ADV7103, which contains potassium citrate and potassium bicarbonate in an extended-release formulation, has recently been approved by the European Medicine Agency (EMA) for dRTA. Recent studies support its use as a first-line treatment, given its efficacy and safety profile."

Journal • Gastrointestinal Disorder • Immunology • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease • ATP6V0A4 • SLC4A1 • WDR72

Long-term clinical outcomes of dRTA patients treated with Sibnayal, an oral twice-daily fixed and prolonged-release combination of potassium bicarbonate and potassium citrate (ESPN 2024) - "Long-term data support the good safety and efficacy profile of Sibnayal® in the treatment of dRTA with adequate control of metabolic acidosis, stable kidney function and significant positive long-term outcomes, notably on growth, lumbar spine BMD and bone metabolism in patients with dRTA treated over 6 years in average."

Clinical • Clinical data • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Rare Diseases • Renal Calculi

TREATMENT OF PRIMARY AND SECONDARY DISTAL RENAL TUBULAR ACIDOSIS WITH A PROLONGED RELEASE FORMULATION OF POTASSIUM CITRATE AND POTASSIUM BICARBONATE (ERA-EDTA 2024) - "Our data show that treatment with a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in adult dRTA patients can achieve good control of metabolic acidosis and electrolyte disbalance with stable kidney function without the need to escalate the dose of the drug during the follow-up period. The adherence to the treatment remained good with no gastrointestinal side effects."

Chronic Kidney Disease • Gastrointestinal Disorder • Immunology • Metabolic Disorders • Nephrology • Pain • Renal Calculi • Sjogren's Syndrome

Long-term benefits in dRTA patients treated with Sibnayal®, a prolonged-release combination of potassium bicarbonate and citrate: 6-year results (ERA-EDTA 2024) - "Sibnayal®, an oral twice-daily fixed and prolonged- release combination of potassium bicarbonate and potassium citrate3, is registered in the indication of dRTA, whatever the genetic or acquired form, in patients aged 1 year and older... These data confirm the long-term good tolerability profile and efficacy of Sibnayal® in the management of metabolic acidosis, in patients with dRTA. Sibnayal® showed a preventive effect on metabolic acidosis long-term complications in this population."

Clinical • Metabolic Disorders • Nephrology • Rare Diseases

Trends in Usage and Cost of Potassium Citrate and Alternative Alkalinizing Agents for Nephrolithiasis (AUA 2024) - " The Medicare Part D Prescribers Database was used to identify prescriptions specifically by urologists for alkalinizing agents including potassium citrate, potassium bicarbonate, sodium citrate, and sodium bicarbonate... Urologists can generate significant cost savings by prescribing alternative alkalinizing agents. Lowering the cost of alkali therapy is essential to reducing financial toxicity for patients and improving equitable access to preventative stone treatment."

Nephrology • Renal Calculi • Urology

Study Evaluating Patients With Cystinuria (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: Advicenne Pharma | N=97 ➔ 0 | Trial completion date: Aug 2022 ➔ Aug 2025 | Unknown status ➔ Withdrawn | Trial primary completion date: Aug 2022 ➔ Jun 2025

Compliance • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal

Extension Study in Primary Distal Renal Tubular Acidosis (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Advicenne Pharma | Phase classification: P3b ➔ P3 | N=40 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Phase classification • Trial withdrawal • Metabolic Disorders • Nephrology

Study Evaluating Subjects With Distal Renal Tubular Acidosis (clinicaltrials.gov) - P3 | N=3 | Terminated | Sponsor: Advicenne Pharma | N=40 ➔ 3 | Trial completion date: Oct 2024 ➔ Dec 2023 | Not yet recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Dec 2023; Study determined to need design review due to challenge of exposing subjects to rebound metabolic acidosis on placebo arm. New design to be determined in discussion with FDA.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Metabolic Disorders • Nephrology • Pediatrics

Study Evaluating Subjects With Distal Renal Tubular Acidosis (clinicaltrials.gov) - P3 | N=40 | Not yet recruiting | Sponsor: Advicenne Pharma | Trial completion date: Aug 2022 ➔ Oct 2024 | Trial primary completion date: Apr 2022 ➔ Aug 2024

Trial completion date • Trial primary completion date • Metabolic Disorders • Nephrology • Pediatrics

Study Evaluating Patients With Cystinuria and Efficacy and Safety Exploratory Study in the Youngest Children (clinicaltrials.gov) - P2/3 | N=72 | Not yet recruiting | Sponsor: Advicenne Pharma | Trial completion date: Aug 2020 ➔ Jun 2025 | Trial primary completion date: Aug 2020 ➔ May 2025

Trial completion date • Trial primary completion date

Extension Study in Primary Distal Renal Tubular Acidosis (clinicaltrials.gov) - P3b | N=40 | Not yet recruiting | Sponsor: Advicenne Pharma | Trial completion date: Mar 2021 ➔ Mar 2025 | Trial primary completion date: Mar 2021 ➔ Jan 2025

Trial completion date • Trial primary completion date • Metabolic Disorders • Nephrology

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103). (PubMed, Nefrologia (Engl Ed)) - "Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters."

Journal • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Pediatrics

Advicenne SA (BIO 2022) - "Our lead product ADV7103 is currently approved for the treatment of distal renal tubular acidosis (dRTA) in Europe and entering the PIII development phase in the United States. This product is also under development for Cystinuria in both Europe and the United States."

Metabolic Disorders • Nephrology • Renal Disease

Improved growth of a child with primary distal renal tubular acidosis after switching from a conventional alkalizing treatment to a new prolonged-release formulation containing potassium citrate and potassium bicarbonate: lessons for the clinical nephrologist. (PubMed, J Nephrol) - No abstract available

Journal • Metabolic Disorders • Nephrology

Lived experiences of patients with distal renal tubular acidosis treated with ADV7103 and of their caregivers: a qualitative study. (PubMed, Orphanet J Rare Dis) - P3 | "Qualitative interviews show that dRTA and its treatment have a significant impact on QoL of patients and parents and that ADV7103 helps improve daily-life and reduces treatment burden, resulting in greater overall satisfaction of the patients and their families. Trial registration EU Clinical Trials Register, EudraCT 2013-003828-36 on the 3rd of September 2013."

Journal • Metabolic Disorders • Nephrology • Otorhinolaryngology • Pediatrics • Rare Diseases

[VIRTUAL] ARENA2: Decentralized Clinical Trial for Patients With Primary Distal Renal Tubular Acidosis (dRTA) (KIDNEY WEEK 2021) - P3 | "Description ARENA2 ( A lkalization for REN al A cidosis) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in patients with primary dRTA (NCT03644706), designed to compare the efficacy of oral ADV7103 vs. placebo in preventing metabolic acidosis and hypokalemia, followed by an optional open-label extension...Enrollment will open July 2021. Contact Larry Greenbaum at lgreen6@emory.edu."

Clinical • Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease

[VIRTUAL] Improvement in Metabolic Control in Patients with Distal Renal Tubular Acidosis (dRTA) After Switching from Standard of Care to ADV7103 (KIDNEY WEEK 2021) - P3 | "All three patients demonstrated better adherence with ADV7103 as compared to SoC. This small cohort of patients reported improved palatability and satisfaction with ADV7103 treatment as reasons for improved medication adherence and this increased adherence is believed to have had a direct impact on the overall metabolic control achieved throughout the study."

Clinical • Dyspepsia • Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease

Study Evaluating Subjects With Distal Renal Tubular Acidosis (clinicaltrials.gov) - P3; N=40; Not yet recruiting; Sponsor: Advicenne Pharma; Trial completion date: Feb 2021 ➔ Aug 2022; Trial primary completion date: Feb 2021 ➔ Apr 2022

Clinical • Trial completion date • Trial primary completion date • Metabolic Disorders • Nephrology • Pediatrics

Gitelman Syndrome in Pregnancy: A Clinical Challenge. (PubMed, Z Geburtshilfe Neonatol) - " Increased need for potassium and magnesium supplementation should be the critical considerations when managing pregnant patients with GS."

Clinical • Journal • Anesthesia • Nephrology

[VIRTUAL] Distal (Type I) Renal Tubular Acidosis Associated With Primary Sclerosing Cholangitis (ACG 2020) - "Encephalopathy responded to lactulose/rifaximin administration. Correction of acidosis should be accomplished using potassium citrate – potassium bicarbonate tablets as they contain more mEq of bicarbonate per tablet than commonly used sodium bicarbonate. This abstract helps raise awareness amongst fellows and practicing gastroenterologists in recognizing PSC as a cause of dRTA."

CNS Disorders • Complement-mediated Rare Disorders • Endocrine Disorders • Fibrosis • Genetic Disorders • Hepatic Encephalopathy • Hepatology • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Movement Disorders • Nephrology • Primary Biliary Cholangitis • Renal Disease • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Transplantation

[VIRTUAL] ADV7103 Treatment Adherence in Patients with Distal Renal Tubular Acidosis (DRTA) (ISPOR 2021) - "Adherence levels ≥75% were maintained in the majority of patients (79.3%) over 24 months supporting the good acceptance and tolerability of ADV7103 in maintaining long-term metabolic control in patients with dRTA."

Clinical • Metabolic Disorders • Nephrology • Pediatrics