Latest Review Date: October 2024

Category:  Pharmacy                                                           

POLICY:

Use of a cartridge device (e.g. RELiZORB™ immobilized lipase cartridge) to deliver digestive enzymes to enteral formula is considered  investigational for all indications.

DESCRIPTION OF PROCEDURE OR SERVICE:

A digestive enzyme cartridge (e.g., RELiZORB™) is a medical device designed to mimic the normal function of pancreatic lipase for use in adults on enteral tube feeding who have trouble breaking down and absorbing fats. It is a point-of-care device designed to fit in line with enteral feeding circuits. The device is designed to hydrolyze (break down) fats present in enteral formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. This breakdown of fats is intended to mimic the function of the enzyme lipase in patients who do not excrete sufficient levels of pancreatic lipase.

RELiZORB is comprised of a cylindrical, hollow cartridge with a single inlet port and a single outlet port connection. Inside the cartridge, there are small white beads. The digestive enzyme, lipase, is covalently bound to the small white beads. The lipase-bead complex, iLipase™ (immobilized lipase), is retained within the cartridge during use by filters on both ends of the cartridge. The fat in enteral formulas is hydrolyzed as it comes in contact with iLipase as the formula passes through the cartridge.

KEY POINTS:

This evidence has been updated with a literature review using the PubMed database. The most recent literature review was performed through October 8, 2024.

SUMMARY OF EVIDENCE:

For individuals who have pancreatic insufficiency and who receive RELiZORB as an adjunct to maintenance enteral feeding, the evidence consists of multicenter crossover trials and retrospective case series. The long term efficacy of RELiZORB has not been established at this time. Further corroboration of these results is needed in high-quality RCTs with larger sample size and without concomitant pancreatic enzyme replacement therapy. The evidence is insufficient to determine the effects of the technology on health outcomes.

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS

Not applicable.

KEY WORDS:

Relizorb, digestive enzyme, enteral feeding, tube feeding, enzyme cartridge, RELiZORB™, pancreatic insufficiency, iLipase®, immobilized lipase

APPROVED BY GOVERNING BODIES:

The Food and Drug Administration (FDA) cleared RELiZORB in 2015, through the Premarket Notification process, subsequent clearance (K163057) issued on July 12, 2017. RELiZORB is indicated for use in pediatric patients (ages 2 years and above) and adult patients to hydrolyze fats in enteral formula.

August 2023: The clearance for ages 2 to <5 years is based on a retrospective evaluation of real-world data in patients 2 to <5 years’ old who received enteral formula administered through RELiZORB as part of an enteral feeding regimen.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.   

CURRENT CODING:

HCPCS Codes:

REFERENCES:

1. Abu-El-Haija, M., Uc, A., et al. “Nutritional Considerations in Pediatric Pancreatitis: A Position Paper from the NASPHAN Pancreas Committee and ESPHAN Cystic Fibrosis/Pancreas Working Group. JPGN 2018;67:131-143.
2. Alcresta Therapeutics. Relizorb: (Immobilized Lipase) Cartridge, 2017. Available at: relizorb.com/.
3. Alcresta Therapeutics. Absorption and Safety With Sustained Use of Relizorb Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding. www.cff.org/Trials/Finder/details/470/ASSURE-Study-of-Relizorb-in-people-with-CF-who-receive-enteral-tube-feeding.
4. BioSpace, October 28, 2016. PRNewswire: Alcresta’ Relizorb increases fat absorption in adult and pediatric patients with cystic fibrosis receiving enteral nutrition. Newton, Massachusetts. Available at: www.biospace.com/news_story.aspx?StoryID=437369.
5. ClinicalTrials.gov. Safety, Tolerability and Fat Absorption Using Enteral Feeding In-line Enzyme Cartridge (Relizorb), ClinicalTrials.gov Identifier: NCT02598128. Last updated: June 2016. Available at: clinicaltrials.gov/ct2/show/NCT02598128.
6. Cystic Fibrosis Foundation. Pancreatic Enzymes Clinical Care Guidelines. 2019. https://www.cff.org/Care/Clinical-Care-Guidelines/Nutrition-and-GI-Clinical-CareGuidelines/Pancreatic-Enzymes-Clinical-Care-Guidelines/.
7. Freedman S, Orenstein D, Black P, et al. Increased fat absorption from enteral formula through an in-line digestive cartridge in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 2017;65(1):97–101.
8. Freedman SD, Wyatt C, Stevens J, et al. Absorption and safety with sustained use of Relizorb evaluation (ASSURE) study in patients with cystic fibrosis receiving enteral feeding. J Pediatr Gastroenterol Nutr. 2018;67(4):527-532.
9. Freeman AJ, Maqbool A, Bellin M, et al. Medical management of chronic pancreatitis in children: a position paper by the North American society of pediatric gastroenterology, hepatology and nutrition pancreas committee. J Pediotr Gostroenterol Nutr. 2021;72: 324- 340.
10. Giguere-Rich C, et al. Use of an in-line digestive cartridge with enteral nutrition improves the weight trajectory of 2 children with cystic fibrosis complicated by another medical diagnosis. Nutr Clinical Pract. 2018;33(2): 286-294.
11. Hayes, Inc. Search and summary, Relizorb (Alcresta Pharmaceuticals). February 4, 2016.www.hayesinc.com/hayes/publications/search-summary/hss-relizorb3607/ No longer accessible.
12. Hendrix SJ, Flume PA, First ER, et al. Improvements in anthropometric measures and gastrointestinal tolerance in patients with cystic fibrosis by using a digestive enzyme cartridge with overnight enteral nutrition.  Nurt Clin Pract. 2022 Apr;37(2):344-350.
13. Maki, J., Neelagiri, M., Olshaw, B., Devarakonda, S., Loring, G. ePS05.2 Novel point of care immobilized lipase device (EFIC™) is compatible with a range of nutritional formulas and can simplify delivery of hydrolyzed fat during tube feeding, 1993. Journal of Cystic Fibrosis. Available at: www.cysticfibrosisjournal.com/article/S1569-1993 (15)30161-2/pdf.
14. Maki, J. et al. ePS05.2 Novel point of care immobilized lipase device (EFIC™) is compatible with a range of nutritional formulas and can simplify delivery of hydrolyzed fat during tube feeding. Journal of Cystic Fibrosis, June 2015. Volume 14, S50
15. Medscape, LLC. FDA clears Relizorb for use with enteral tube feedings. Medscape, LLC. New York, NY. December 03, 2015.Available at: www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm?ID=DEN150001.
16. Sathe et al. Evaluation of the effectiveness of in-line immobilized lipase cartridge in enterally fed patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2021; 72 :18-23.
17. Schwarzenberg SJ, Hempstead SE, McDonald CM, et al. Enteral tube feeding for Individuals with cystic fibrosis: Cystic Fibrosis Foundation evidence-Informed guidelines. 2016;15(6):724-735.
18. Stevens T., Conwell D.L. Exocrine pancreatic insufficiency www.uptodate.com/contents/cystic-fibrosis-nutritional-issues?source=search_result&search=digestive%20enzymes%20cystic&selectedTitle=1~150
19. Somaraju URR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2020;8(8):CD008227. Published 2020 Aug 5. doi:10.1002/14651858.CD008227.pub4
20. Stevens J, Wyatt C, Brown P, Patel D, Grujic D, Freedman SD. Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding. J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):527-532.
21. U.S. Food and Drug Administration. Relizorb enzyme packed cartridge. 510(k) No. K163057 (traditional). Silver Spring, MD: FDA; July 12, 2017.
22. U.S. Food and Drug Administration. 510(k) Summary. K161247. Relizorb™. 2016 June 30. Available at URL address: https://www.accessdata.fda.gov/cdrh_docs/pdf16/K161247.pdf

POLICY HISTORY:

Medical Policy Group, August 2017

Medical Policy Administration Committee, September 2017

Medical Policy Group, August 2017 (6): New Policy

Medical Policy Group, June 2018: Quarterly Coding Update, July 2018.  Added new CPT code Q9994 to Current Coding.

Medical Policy Group, December 2018: 2019 Annual Coding Update.  Added HCPC code B4105 to the Current coding section and moved HCPC code from Current coding section to Previous coding.  Created Previous coding section to include code Q9994.

Medical Policy Group, December 2019 (6): Updates to Description, Key Points, Governing Bodies, Key Words (iLipase™) and References. No change to policy intent.

Medical Policy Group, December 2020 (6): Updates to Key Points and Governing Bodies. No change to policy intent.

Medical Policy Group, December 2021 (6): Updates to Key Points, Coding and References. No change to policy intent.

Medical Policy Group, October 2022(6): Update to References.  No change to policy intent.

Medical Policy Group, October 2023 (6): Updates to Description, Key Points, Governing Bodies, Key Words, Benefit Application and References.

Medical Policy Group, October 2024 (6): Updates to Key Points, Practice Guidelines and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.