Commercial

Policy

MPPolicyPub

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member's medical needs and condition.

MEDICALLY NECESSARY

INITIAL THERAPY
Pozelimab-bbfg (Veopoz^®) is considered medically necessary and, therefore, covered for the treatment of individuals one year of age and older with cluster of differentiation (CD)55-deficient protein-losing enteropathy (PLE), also known as CHAPLE (complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy) disease, when ALL of the following are met: 

• Presence of laboratory-confirmed genotype of biallelic CD55 loss-of-function mutation
• Presence of at least ONE of the following symptoms, attributable to CHAPLE disease, within the last six months (unless the individual is currently being treated with eculizumab [Soliris^®] therapy with the willingness by the professional provider to discontinue the treatment before initiating treatment with pozelimab-bbfg [Veopoz]):
• Hypoalbuminemia (serum albumin concentration of 3.2 g/dL or less)
• Facial edema
• Peripheral edema
• Diarrhea
• Abdominal pain
• Thromboembolic event(s)
• Completion or update of meningococcal vaccination (in serogroups A, C, W and Y, and serogroup B) at least two weeks prior to the planned start of pozelimab-bbfg (Veopoz) therapy 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)
• Pozelimab-bbfg​ (Veopoz) is ordered by, or in consultation with, a professional provider who has the expertise to treat CHAPLE disease (e.g., Gastroenterology, Hematology, Immunology, rare genetic hematologic disease specialist)
• The individual will not be concurrently treated with any other complement inhibitors ​
• The individual does not have unresolved Neisseria meningitidis infection at the start of treatment with pozelimab-bbfg (Veopoz)

CONTINUATION THERAPY
Continuation of pozelimab-bbfg (Veopoz) will be considered to be medically necessary when ALL of the following are met:

• Hypoalbuminemia has improved or resolved from baseline levels
  
• Symptoms have improved or resolved from baseline levels
  

EXPERIMENTAL/INVESTIGATIONAL

All other uses of pozelimab-bbfg (Veopoz) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.​

Guidelines

Description

MPDescriptionPub

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (PLE) or cluster of differentiation (CD)55-deficient PLE (CHAPLE disease) is an ultra rare disease (estimated at 100 individuals worldwide) caused by a recessive homozygous variant in the gene that encodes CD55, a complement regulating protein. The complement system is responsible for providing a defense for the individual by microbe destruction and immunity modulation. CD55 attaches to the surface of cells and prevents overactivation of the terminal complement system. Lack of CD55 results in intestinal inflammation and primary intestinal lymphangiectasia. The disease is characterized by hypoalbuminemia, hypogammaglobulinemia (resulting in susceptibility to recurrent bacterial infections such as Streptococcus pneumonia, Haemophilus influenzae, and Neisseria meningitidis), gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea), edema (facial and peripheral), and chronic malabsorption that results in micronutrient deficiencies (e.g., iron, ferritin, folate, calcium, magnesium, vitamin B12, vitamin D). Severe cases could result in the presence of pleural or pericardial effusions or abdominal ascites. Individuals experience anemia, growth retardation, recurrent respiratory infections, gastrointestinal obstruction and/or perforation, and severe thromboembolic vascular occlusions. The disease is often identified in infancy or early childhood due to the presence of clinical and laboratory evidence, but cases of the disease have also been identified in adults. Individuals with CHAPLE disease are treated with supportive care, including albumin and blood transfusions, dietary management (low fat, high protein, high medium-chain triglycerides), intravenous immunoglobulin (IVIG), immunosuppressive therapy, bowel resections, and supplementation of micronutrients and vitamins. There have been reports in the medical literature of individual case studies and small case series (Hagin et al. 2021; Hanna et al. 2019; Kaya 2023; Kurolap et al. 2017; Kurolap et al. 2019; Kurolap et al. 2023; Ohlsson et al. 2023; Ozen 2019; Ozen et al. 2021) in which individuals with CHAPLE disease were treated successfully with eculizumab (Soliris). The use is off-label as CHAPLE disease is not an FDA-approved use of the drug and there have not been any clinical trials reporting the efficacy and safety of the drug used for this indication. The normal course of the disease can result in early mortality due to thromboembolic events.

Pozelimab-bbfg (Veopoz) is a monoclonal immunoglobulin G4 (IgG4) antibody directed against the terminal complement protein C5 that inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking the formation of the membrane-attack complex (C5b-C9, a structure mediating cell lysis).

The safety and efficacy of pozelimab-bbfg (Veopoz) were evaluated in a phase 2-phase 3, single-arm, multicenter, historically-controlled, open label clinical trial (NCT04209634). The primary outcome was the percentage of individuals who achieved normalization of serum albumin concentrations and improvement in their symptoms by week 24. Some secondary outcomes were number of individuals who had improvement in the signs and symptoms of the disease, percentage of individuals who maintained disease control, number of individuals with albumin infusions, time to normalization of serum albumin concentrations, absolute values of immunoglobulins (IgG, IgM, IgA) at week 24, time to normalization of total protein and percentage of individuals whose levels normalized, number of hospitalization days, quality of life measures, and safety measures. The treatment group consisted of ten individuals ranging from three to nineteen years of age. The mean baseline serum albumin concentration for the individuals was 2.2 g/dL (range 1.1 to 2.9 g/dL). All ten of the individuals achieved normalization of their serum albumin and IgG concentrations by week 12 and maintained normal levels through at least 72 weeks of therapy. Seven of the participants underwent an abdominal computed tomography (CT) or magnetic resonance imaging (MRI) study both before and during treatment. All seven of the studies demonstrated resolution of mesenteric lymphadenopathy and small bowel wall thickening/enhancement. By week 36, all evaluable individuals had resolved the facial edema. By week 24, all evaluable individuals had resolved the peripheral edema. By week 48, the nine evaluable individuals increased their mean change from baseline in their weight-for-age and height-for-age percentiles by 15.5 and 11.2 respectively. Prior to the clinical trial, five of the ten involved individuals had received a total of 60 albumin transfusions in the previous year (48 weeks). In the year (48 weeks) after starting treatment with pozelimab-bbfg (Veopoz), only one individual required one albumin transfusion. Prior to the clinical trial, nine of the ten involved individuals has been hospitalized for a total of 268 days in the previous year (48 weeks). In the year (48 weeks) after starting treatment with pozelimab-bbfg (Veopoz), only two individuals were hospitalized for a total of seven days. Nine of the participants experienced a total of 47 treatment-emergent adverse events, but most were felt to be unrelated to the treatment. Treatment-related adverse events were considered to be mild, and no participant withdrew from the study or stopped treatment permanently.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Coding

CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)

HCPCS Level II Code Number(s)

Revenue Code Number(s)

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History