Pozelimab-bbfg (Veopoz)

Number: 1043

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses pozelimab-bbfg (Veopoz) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of pozelimab-bbfg (Veopoz) is required of all Aetna participating providers and members in applicable plan designs. For precertification of pozelimab-bbfg (Veopoz), call (866) 752-7021, or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies.  For information on site of service for pozelimab-bbfg (Veopoz), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Criteria for Initial Approval

   Aetna considers pozelimab-bbfg (Veopoz) medically necessary for treatment of CD55-deficient protein-losing enteropathy (PLE) (also known as CHAPLE disease) when all of the following criteria are met:

   1. The member has a confirmed biallelic CD55 loss-of-function mutation detected by genotype analysis; and 
   2. The member has hypoalbuminemia (serum albumin concentration of less than or equal to 3.2 g/dL); and
   3. The member has one or more of the following signs and symptoms of CD-55 PLE within the past 6 months:
      
      
      1. Abdominal pain
      2. Diarrhea
      3. Peripheral edema
      4. Facial edema.

   Aetna considers all other indications as experimental and investigational. 

2. Continuation of Therapy

   Aetna considers continuation of pozelimab-bbfg (Veopoz) therapy medically necessary in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and member demonstrates a positive response to therapy (e.g., normalization of serum albumin, improvement in signs and symptoms of disease, and/or decrease in number of hospitalizations and infections).

Dosage and Administration

Veopoz is supplied as 400 mg/2 mL (200 mg/mL) in single-dose vials. Below includes FDA-approved labeled recommendations.

The recommended dosage of Veopoz is as follows:

• Day 1 (Loading Dose): administer a single 30 mg/kg dose by intravenous infusion after dilution;
• Day 8 and Thereafter (Maintenance Dosage): Inject 10 mg/kg as a subcutaneous injection once weekly starting on Day 8
  
  
  • The maintenance dosage may be increased to 12 mg/kg once weekly if there is inadequate clinical response after at least 3 weekly doses (i.e., starting from Week 4).
  • The maximum maintenance dosage is 800 mg once weekly.
  • Doses greater than 400 mg require 2 injections.

Source: Regeneron Pharmaceuticals, 2023

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
82040	Albumin; serum, plasma or whole blood
96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96369	Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); initial, up to 1 hour, including pump set-up and establishment of subcutaneous infusion site(s)
HCPCS codes covered if selection criteria are met:
Pozelimab-bbfg (Veopoz) –no specific code
ICD-10 codes covered if selection criteria are met:
D84.1	Defects in the complement system [CD55-deficient protein-losing enteropathy (PLE)]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Veopoz is indicated for the treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease.

Pozelimab-bbfg, branded as Veopoz (Regeneron Pharmaceuticals, Inc.), is a human, monoclonal immunoglobulin G4 (IgG4) antibody that blocks the activation of complement factor C5 in the complement pathway.

CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE (complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy) disease, is a rare, inherited immune disease caused by mutations in the complement regulator CD55 gene which results in an overactive complement system. Clinical presentation can include hypoproteinemia, hypogammaglobulinemia, bowel obstruction, enteritis, lymphangiectasia, and edema. Patients may report abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, and swelling. Severe thrombotic vascular occlusions can also occur, which can be life-threating (FDA, 2023; Yu and Ardoin, 2021).

In August 2023, Veopoz, a complement inhibitor, became the first FDA-approved treatment for CHAPLE disease. Approval was based on the safety and efficacy outcomes of pozelimab-bbfg that was evaluated in an open-label, single-arm, phase 2/3 study (ClinicalTrials.gov Identifier: NCT04209634) in which patients had achieved and maintained "normalization" of serum albumin concentrations, as well as, had a reduction in number of hospitalizations and albumin transfusions, compared to pre-treatment data (FDA 2023; Regeneron Pharmaceuticals, 2023).

The primary objective of the single-arm study was to determine the effect of pozelimab-bbfg on active CD55-deficient PLE (CHAPLE). This study included 10 patients (3 to 19 years of age) with confirmed genotype of biallelic CD55 loss-of-function mutation who had active CD55-deficient PLE, defined as hypoalbuminemia (serum albumin concentration of less than or equal to 3.2 g/dL) with one or more of the following signs or symptoms within the last 6 months: abdominal pain, diarrhea, peripheral edema, or facial edema. Patients received a single 30 mg/kg loading dose of pozelimab-bbfg (Veopoz) administered by intravenous infusion, followed by once weekly weight-tiered maintenance dosage, administered as a subcutaneous injection starting one week after the loading dose. All patients received meningococcal vaccination prior to treatment, and antibacterials for prophylaxis of meningococcal infection. The median time for serum albumin to reach at least 3.5 g/dL was 15.5 days (n=10; 95% CI: 8 to 28). All 10 patients achieved a serum albumin concentration of at least 3.5 g/dL by week 12, which was maintained through at least 72 weeks. All 10 patients also demonstrated a reduction in the number of hospitalizations and number of albumin transfusions over the first 48 weeks of treatment as compared to the 48 weeks prior to treatment. Five of the 10 patients received a total of 60 transfusions in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, one patient received one albumin transfusion. Nine of the 10 patients were hospitalized for a total of 268 days in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, two patients were hospitalized for a total of 7 days. Furthermore, serum IgG concentrations reached "normal" values for age in all patients within the first 12 weeks of treatment; improvement was maintained through at least 72 weeks of treatment (FDA, 2023; Regeneron Pharmaceuticals, 2023).

Veopoz carries a labeled black box warning for serious meningococcal infections because life-threatening and fatal meningoccal infections have occurred in patients treated with complement inhibitors. Therefore, the label recommends completing or updating meningococcal vaccination at least 2 weeks prior to administering the first dose of Veopoz, unless the risks of delaying therapy outweigh the risks of developing meningococcal infection. Follow the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor. Patients receiving Veopoz are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Healthcare providers should monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Veopoz is considered contraindicated in patients with unresolved N. meningitidis infection.

Labeled warnings and precautions include other bacterial infection, systemic hypersensitivity, and immune complex formation. The most common adverse reactions (in two or more patients) include upper respiratory tract infection, fracture, urticaria, and alopecia.

Intravenous immunoglobulin may decrease pozelimab-bbfg concentrations. Therefore, concomitant use should be avoided. 

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References