ALLN-177, oral enzyme therapy for hyperoxaluria

James E. Lingeman, Gyan Pareek, Linda Easter, Rita Pease, Danica Grujic, Lee Brettman, Craig B. Langman*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: 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. Trial registration: Clinicaltrials.gov NCT02289755.

Original languageEnglish (US)
Pages (from-to)601-608
Number of pages8
JournalInternational urology and nephrology
Volume51
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Hyperoxaluria
Enzyme Therapy
Oxalates
Urine
Diet Therapy
Dietary Calcium
Calcium Oxalate
Kidney Calculi
Meals
Diet
Safety
Therapeutics

Keywords

  • Bariatric surgery
  • Enteric hyperoxaluria
  • Nephrolithiasis
  • Oxalate

ASJC Scopus subject areas

  • Nephrology
  • Urology

Cite this

Lingeman, J. E., Pareek, G., Easter, L., Pease, R., Grujic, D., Brettman, L., & Langman, C. B. (2019). ALLN-177, oral enzyme therapy for hyperoxaluria. International urology and nephrology, 51(4), 601-608. https://doi.org/10.1007/s11255-019-02098-1
Lingeman, James E. ; Pareek, Gyan ; Easter, Linda ; Pease, Rita ; Grujic, Danica ; Brettman, Lee ; Langman, Craig B. / ALLN-177, oral enzyme therapy for hyperoxaluria. In: International urology and nephrology. 2019 ; Vol. 51, No. 4. pp. 601-608.
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Lingeman, JE, Pareek, G, Easter, L, Pease, R, Grujic, D, Brettman, L & Langman, CB 2019, 'ALLN-177, oral enzyme therapy for hyperoxaluria', International urology and nephrology, vol. 51, no. 4, pp. 601-608. https://doi.org/10.1007/s11255-019-02098-1

ALLN-177, oral enzyme therapy for hyperoxaluria. / Lingeman, James E.; Pareek, Gyan; Easter, Linda; Pease, Rita; Grujic, Danica; Brettman, Lee; Langman, Craig B.

In: International urology and nephrology, Vol. 51, No. 4, 01.04.2019, p. 601-608.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ALLN-177, oral enzyme therapy for hyperoxaluria

AU - Lingeman, James E.

AU - Pareek, Gyan

AU - Easter, Linda

AU - Pease, Rita

AU - Grujic, Danica

AU - Brettman, Lee

AU - Langman, Craig B.

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N2 - Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: 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. Trial registration: Clinicaltrials.gov NCT02289755.

AB - Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: 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. Trial registration: Clinicaltrials.gov NCT02289755.

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Lingeman JE, Pareek G, Easter L, Pease R, Grujic D, Brettman L et al. ALLN-177, oral enzyme therapy for hyperoxaluria. International urology and nephrology. 2019 Apr 1;51(4):601-608. https://doi.org/10.1007/s11255-019-02098-1