reloxaliase (ALLN-177) / Allena Pharma - LARVOL DELTA

Systematic review of pharmacological, complementary, and alternative therapies for the prevention of calcium oxalate stones. (PubMed, Asian J Urol) - "Modalities that were found to reduce known urinary risk factors were tolvaptan, cranberry juice, magnesium citrate, oxalate-degrading enzyme ALLN-177, and malic acid. Therapies that reduced urinary risk factors and stone formation were Phyllanthus niruri, rice bran, and magnesium hydroxide. Several of the identified therapies may provide prophylactic benefits for CaOx stone formation and may be useful for inclusion in guidelines for kidney stone prevention."

Journal • Review • Nephrology • Renal Calculi • Urolithiasis

[VIRTUAL] Kidney stone risk and association with urine oxalate (UOx) levels in enteric hyperoxaluria (EH) (AUA 2020) - "URIROX-1 is the first RCT examining a specific therapy targeting UOx reduction in EH, a clinically challenging and understudied population.  The URIROX-1 study demonstrated a clinically meaningful reduction of 24h UOx in EH subjects on reloxaliase. Although the short duration of this study precludes assessment of its effect on KS risk, the URIROX-1 data underscores the utility of 24h UOx as a surrogate marker of KS risk and the value of the ongoing URIROX-2 adaptive design trial to quantify clinical benefits of reloxaliase with respect to KS disease progression and renal function. Source of Funding: Allena pharmaceuticals"

Late-breaking abstract • Renal Calculi

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3 | N=92 | Terminated | Sponsor: Allena Pharmaceuticals | Active, not recruiting ➔ Terminated; Interim Analysis -

Trial termination • Nephrology

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3 | N=92 | Active, not recruiting | Sponsor: Allena Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=200 ➔ 92 | Trial completion date: Nov 2023 ➔ Apr 2022 | Trial primary completion date: Nov 2023 ➔ Mar 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Nephrology

"Other studies pending: #reloxaliase (Allena), #PUSH (#niddk) and Sweetstone: #flozin (empa) vs placebo in UA and Ca SF; #SYNB8802 and #NOV-001 for enteric hyperoxaluria; #lumasiran for CaOx stones" (@weddellite)

Clinical • Nephrology

Pilot study of reloxaliase in patients with severe enteric hyperoxaluria and hyperoxalemia. (PubMed, Nephrol Dial Transplant) - No abstract available

Clinical • Journal • Nephrology

[VIRTUAL] Pharmacodynamic (PD) Profiling of Reloxaliase in Patients with Severe Hyperoxaluria (KIDNEY WEEK 2020) - "Reloxaliase was well tolerated; the absence of formate accumulation further supports its safety. The lack of REL absorption, in addition to supporting low potential for systemic toxicity, confirms its site of action within the GI tract. This best aligns with the pathophysiology of EH as evidenced by the substantial reduction in both POx and UOx in EH subjects with CKD/ESRD."

Clinical • PK/PD data • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

[VIRTUAL] Establishing Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria (URIROX-2) (KIDNEY WEEK 2020) - "of URIROX-1, the first Phase 3 study, and COVID-19, led to streamlining of the second pivotal Phase 3 study, URIROX-2. Notably, a higher than expected KS event rate in URIROX-1 reduced the sample size required to accrue enough KS events to enable demonstration of a meaningful reduction in KS disease progression. URIROX-2 is double-blind, randomized placebo-controlled trial recruiting 200 subjects ≥18 years with EH and KS, eGFR ≥30 mL/min/1.73m2 and UOx ≥50 mg/d."

Clinical • Chronic Kidney Disease • Gastrointestinal Disorder • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Calculi • Renal Disease • Urolithiasis

[VIRTUAL] Safety and Efficacy of Reloxaliase in Enteric Hyperoxaluria (EH): An Aggregate Review of Completed Studies (KIDNEY WEEK 2020) - "Reloxaliase reduces 24-hr UOx excretion and is well tolerated in EH patients independent of eGFR, dosing frequency, or duration of treatment. Further studies are ongoing to assess the long-term benefits of reloxaliase and its potential to decrease kidney stone events and preserve kidney function. Funding: Commercial Support"

Clinical • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=200; Recruiting; Sponsor: Allena Pharmaceuticals; N=400 ➔ 200; Trial completion date: Jan 2023 ➔ Nov 2023; Trial primary completion date: Jan 2023 ➔ Nov 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Renal Calculi

[VIRTUAL] Results of a Phase 2 Study of Reloxaliase in Subjects with Advanced Oxalate Disorders (AUA 2020) - "A substantial reduction in both POx and UOx was demonstrated in EH subjects with CKD. The mechanism of action of reloxaliase, to degrade oxalate in the GI tract, aligns with the pathophysiology of EH which involves excess oxalate absorption. To our knowledge, this is the first demonstration of a pharmacological therapy for POx reduction in subjects with EH and advanced CKD."

Clinical • P2 data • Chronic Kidney Disease • Nephrology • Renal Calculi • Renal Disease

Evaluate the Effect of ALLN-177 in Reducing Urinary Oxalate in Patients With Secondary Hyperoxaluria and Kidney Stones Over 28 Days (clinicaltrials.gov) - P2; N=44; Not yet recruiting; Sponsor: Allena Pharmaceuticals

New P2 trial • Biosimilar

Evaluate the Effect of ALLN-177 in Reducing Urinary Oxalate in Patients With Hyperoxaluria and Kidney Stones (clinicaltrials.gov) - P2b; N=60; Active, not recruiting; Sponsor: Allena Pharmaceuticals; Recruiting ➔ Active, not recruiting; Phase classification: P2 ➔ P2b; Trial primary completion date: Mar 2016 ➔ Nov 2016

Enrollment closed • Phase classification • Trial primary completion date • Biosimilar

Evaluate ALLN-177 in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=115; Completed; Sponsor: Allena Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion

Study of ALLN-177 in Patients Aged 12 Years or Older With Enteric or Primary Hyperoxaluria and Hyperoxalemia (clinicaltrials.gov) - P2; N=15; Completed; Sponsor: Allena Pharmaceuticals; Recruiting ➔ Completed

Clinical • Trial completion

ALLN-177, oral enzyme therapy for hyperoxaluria. (PubMed, Int Urol Nephrol) - P2; "ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria."

Journal

Establishing Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria (URIROX-2) (KIDNEY WEEK 2019) - "Reloxaliase (ALLN-177) is a first-in-class oral enzyme therapy that achieves its therapeutic effect by degrading oxalate in the GI tract, resulting in less oxalate absorption and lower urinary oxalate (UOx) excretion...This international trial is registered on ClinicalTrials.gov (NCT03846090) (funded by Allena Pharmaceuticals) is currently enrolling subjects. Information on becoming a clinical trial site can be obtained by calling (617) 467-4577 x398 or by email: clinical302@allenapharma.com"

Clinical

Pilot Study of Reloxaliase in Subjects with Severe Enteric Hyperoxaluria and Hyperoxalemia: A Pro Tem Analysis of Study ALLN-177-206 (KIDNEY WEEK 2019) - "These preliminary data support further testing of reloxaliase in patients with severe EH. To our knowledge, this is the first therapeutic reduction in plasma oxalate in patients with EH and CKD with oxalosis."

Clinical

Evaluate ALLN-177 in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=124; Active, not recruiting; Sponsor: Allena Pharmaceuticals; Recruiting ➔ Active, not recruiting; Trial primary completion date: Jul 2019 ➔ Oct 2019

Clinical • Enrollment closed • Trial primary completion date

Study of ALLN-177 in Patients Aged 12 Years or Older With Enteric or Primary Hyperoxaluria and Hyperoxalemia (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: Allena Pharmaceuticals; Trial primary completion date: Jun 2019 ➔ Dec 2019

Clinical • Trial primary completion date

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=400; Recruiting; Sponsor: Allena Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Allena Pharmaceuticals; Trial primary completion date: Dec 2020 ➔ Jan 2023

Clinical • Trial primary completion date

URIROX-2: Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Allena Pharmaceuticals

Clinical • New P3 trial