Clinical Policy: Fecal Microbiota, Live-jslm (Rebyota)

Reference Number: CP.PHAR.613
Effective Date: 03.01.23
Last Review Date: 02.26
Line of Business: Commercial, HIM, Medicaid

[Coding Implications](Coding Implications)
[Revision Log](Revision Log)

See Important Reminder at the end of this policy for important regulatory and legal information.

Description

Fecal microbiota, live-jslm (Rebyota™) is a fecal microbiota suspension manufactured from human fecal matter sourced from qualified donors.

FDA Approved Indication(s)

Rebyota is indicated for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older, following antibiotic treatment for recurrent CDI.

Limitation(s) of use: Rebyota is not indicated for treatment of CDI.

Policy/Criteria

Approval duration: 3 months (1 dose only)

CLINICAL POLICY

Fecal Microbiota, Live-jslm

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

II. Continued Therapy

A. Prevention of Clostridioides difficile Infection

1. Re-authorization is not permitted as the efficacy of repeat courses of Rebyota has not been sufficiently established (see Appendix D).

Approval duration: Not applicable

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:

A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies –

CLINICAL POLICY

Fecal Microbiota, Live-jslm

CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents.

IV. Appendices/General Information

Appendix A: Abbreviation/Acronym Key

CDI: Clostridioides difficile infection
FDA: Food and Drug Administration
IDSA: Infectious Diseases Society of America

Appendix B: Therapeutic Alternatives

This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name only and generic (Brand name*) when the drug is available by both brand and generic.

Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): severe allergic reactions (e.g., anaphylaxis) to any component of Rebyota
• Boxed warning(s): none reported

Appendix D: General Information

• Both the Infectious Diseases Society of America (IDSA) and the American College of Gastroenterology recommend fecal microbiota transplantation for patients experiencing their second or further recurrence of CDI.
• Approximately 35% of CDI patients experience recurrence after the initial treatment and resolution of diarrhea. Of those who have a primary recurrence, 40% will have another CDI episode, and after 2 recurrences, the chance of an additional episode increases to as high as 65%.
• Per the 2017 IDSA Clinical Practice Guidelines for CDI:
  
  • An incident case is one with a new primary symptom onset (i.e., in the previous 8 weeks, there was not an episode of positive symptoms and positive Clostridioides difficile result) and positive Clostridioides difficile assay result.
  • A recurrent infection is an episode of symptom onset with a positive assay result following an episode with positive assay result in the previous 2-8 weeks.
• Per the 2021 IDSA Focused Update for CDI in Adults:
  
  • Fidaxomicin is the preferred first-line treatment for patients with recurrent CDI episodes.

CLINICAL POLICY

Fecal Microbiota, Live-jslm

• Vancomycin (in a tapered and pulsed regimen or as a standard course) is an alternative treatment for CDI recurrence.
• Bezlotoxumab (Zinplava®) is an adjunctive treatment that may be used in addition to standard of care antibiotics for patients with a recurrent CDI episode within the last 6 months.
• Prior to fecal microbiota transplantation, appropriate antibiotic treatments for at least 2 recurrences (i.e., 3 CDI episodes) should be tried.
• Examples of treatment regimens for recurrence:
  
  • Vancomycin 125 mg PO QID for 10 days (may be followed by rifaximin 400 mg PO TID for 20 days)
  • Tapered and pulsed regimens of vancomycin (e.g., vancomycin PO 125 mg QID for 10 to 14 days, then BID for 1 week, then QD for 1 week, then every 2 or 3 days for 2 to 8 weeks)
  • Fidaxomicin 200 mg PO BID for 10 days
  • Fidaxomicin 200 mg PO BID for 5 days followed by once every other day for 20 days
  • Fecal microbiota transplantation
  • Bezlotoxumab 10 mg/kg IV once during administration of standard of care antibiotics
• The Bristol Stool Scale is a tool to define stool types. Types 1-2 indicate constipated stool. Types 6-7 indicate diarrheal stool.
  
  • Type 1: separate hard lumps, like nuts
  • Type 2: sausage-shaped but lumpy
  • Type 3: like a sausage but with cracks on its surface
  • Type 4: like a sausage or snake, smooth and soft
  • Type 5: soft blobs with clear-cut edges (passed easily)
  • Type 6: fluffy pieces with ragged edges, a mushy stool
  • Type 7: watery, no solid pieces (entirely liquid)
• Repeat courses: In the event of treatment failure (i.e., CDI diarrhea) within the first 8 weeks of blinded treatment, participants in the PUNCH CD3 phase 3 study were allowed to receive an open-label second treatment course of Rebyota. However, only 41/180 (22.8%) of patients who received an initial course of Rebyota received this second course, and of those 41, only 22 (53.8% of the patients who received a second treatment course; 12.2% of the original population) ultimately achieved treatment success. Given that this was an open-label treatment and included a relatively small sample, this is considered insufficient data to support a second treatment course at this time. In addition, the FDA label indicates only 1 dose should be administered and does not address repeat courses.

V. Dosage and Administration

VI. Product Availability

Suspension (a single dose is 150 mL)

CLINICAL POLICY

Fecal Microbiota, Live-jslm

Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

CLINICAL POLICY

Fecal Microbiota, Live-jslm

Reviews, Revisions, and Approvals

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.