Inebilizumab-cdon (Uplizna)

Number: 0975

Policy

Note: REQUIRES PRECERTIFICATION

Precertification of inebilizumab-cdon (Uplizna) is required of all Aetna participating providers and members in applicable plan designs. For precertification of inebilizumab-cdon (Uplizna) call (866) 752-7021 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Note: Site of Care Utilization Management Policy applies. 

For information on site of service for inebilizumab-cdon (Uplizna) infusions, see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

1. Aetna considers inebilizumab-cdon (Uplizna) medically necessary for the treatment of neuromyelitis optica spectrum disorder (NMOSD) when all of the following criteria are met:
   
   
   1. Member is anti-aquaporin-4 (AQPR) antibody positive; and
   2. Member exhibits one of the following core clinical characteristics of NMOSD:
      
      
      1. Optic neuritis; or
      2. Acute myelitis; or
      3. Area postrema syndrome (episode of otherwise unexplained hiccups or nausea and vomiting); or
      4. Acute brainstem syndrome; or
      5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic magnetic resonance imaging (MRI) lesions; or
      6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions; and
   3. The member will not receive the requested drug concomitantly with other biologics for the treatment of NMOSD.
2. Aetna considers continuation of inebilizumab-cdon therapy medically necessary when both of the following criteria are met:
   
   
   1. The member demonstrates a positive response to therapy (e.g., reduction in number of relapses); and
   2. The member will not receive the requested drug concomitantly with other biologics for the treatment of NMOSD.
3. Aetna considers inebilizumab-cdon experimental and investigational for all other indications.

See also CPB 0314 - Rituximab or CPB 0314m - Rituximab [Medicare], CPB 0807 - Eculizumab (Soliris).

Dosing Recommendations

Uplizna (inebilizumab-cdon) is available for injection as 100 mg/10 mL solution in a single-dose vial, and must be diluted in 250 mL of 0.9% Sodium Chloride Injection, USP prior to administration.

Uplizna is administered as an intravenous (IV) infusion titrated to completion, approximately 90 minutes. The recommended dosage is:

• Initial dose: 300 mg IV infusion followed 2 weeks later by a second 300 mg IV infusion;
• Subsequent doses (starting 6 months from the first infusion): single 300 mg IV infusion every 6 months.

Note: Hepatitis B virus, quantitative serum immunoglobulins, and tuberculosis screening are required before the first dose. Prior to every infusion, determine if there is an active infection, and premedicate with a corticosteroid, an antihistamine, and an antipyretic. Monitor individuals closely during the infusion and for at least one hour after completion of the infusion.

Source: Viela Bio, 2020

Background

Uplizna (inebilizumab-cdon) is a CD19-directed cytolytic antibody. Inebilizumab, the active ingredient in Uplizna, is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen cluster of differentiation (CD19) resulting in the depletion of B cells. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells, which are generally CD19 positive and CD20 negative (MedImmune, 2020). B cells are believed to play a critical role in neuromyelitis optica spectrum disorders (NMOSD). The safety and efficacy of inebilizumab was evaluated in a clinical trial which led to the U.S. Food and Drug Administration (FDA) approval of Uplizna (inebilizumab-cdon) for the treatment of NMOSD, a rare, relapsing, autoimmune, inflammatory disease of the central nervous system (CNS) that causes blindness and paralysis. The precise mechanism by which Uplizna (inebilizumab-cdon) exerts its therapeutic effects in NMOSD is unknown but is presumed to involve the binding to CD19. Following cell surface binding to B lymphocytes, inebilizumab-cdon results in antibody-dependent cellular cytolysis (Viela Bio, 2020).

NMOSD are inflammatory disorders of the CNS characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and spinal cord, which is thought to impact approximately 4,000 to 8,000 people in the United States (FDA, 2020; Glisson, 2019). Women are more often affected than men, and African Americans are at greater risk than are Caucasians. Approximately 50% of individuals with NMOSD have permanent visual impairment and paralysis caused by NMOSD attacks (FDA, 2020). NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) that selectively binds to its target antigen, aquaporin-4 (AQP4), a water channel protein (Glisson, 2019; Takahashi et al., 2007). NMO-IgG (anti-AQP4) has a direct role in the pathogenesis of NMOSD. Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the CNS (FDA, 2020).

On June 11, 2020, the FDA granted approval for Uplizna (inebilizumab-cdon) injection for intravenous use for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. FDA approval was based on the N-MOmentum trial.

Cree et al. (2019) conducted a multicenter, double-blind, randomized placebo-controlled phase 2/3 study (N-Momentum) to assess the efficacy and safety of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk of attacks and disability in NMOSD. The study included 230 participants diagnosed with NMOSD who were at least 18 years of age or older and had a history of at least one attack requiring rescue therapy in the year before screening or at least two attacks requiring rescue therapy in the 2 years before screening. Exclusions included history of hepatitis B and/or C at screening, and previously treated with immunosuppressant therapies within an interval specified for each such therapy. In the trial, 213 of the 230 patients had antibodies against AQP4 (anti-AQP4 antibody positive). Participants were randomly allocated (3:1) to 300 mg intravenous inebilizumab or placebo, administered on days 1 and 15. Of the 230 participants who were randomly assigned to treatment and dosed, 174 participants received inebilizumab and 56 received placebo. However, of the 213 participants that were anti-AQP4 antibody positive, 161 were randomized to receive treatment with inebilizumab, and 52 were randomized to receive placebo (FDA, 2020). The primary endpoint was time to onset of an NMOSD attack. Efficacy endpoints were assessed in all randomly allocated participants who received at least one dose of study intervention, and safety endpoints were assessed in the as-treated population. The authors found that 21 (12%) of 174 participants receiving inebilizumab had an attack versus 22 (39%) of 56 participants receiving placebo (p < 0·0001). Adverse events occurred in 125 (72%) of 174 participants receiving inebilizumab and 41 (73%) of 56 participants receiving placebo. Serious adverse events occurred in eight (5%) of 174 participants receiving inebilizumab and five (9%) of 56 participants receiving placebo. In the anti-AQP4 antibody positive population there was a 77.3% relative reduction (p < 0.0001). There was no evidence of a benefit in participants who were anti-AQP4 antibody negative (FDA, 2020; Viela Bio, 2020). Cree and colleagues concluded that compared with placebo, inebilizumab reduced the risk of an NMOSD attack, and has the potential application as an evidence-based treatment for patients with NMOSD.

According to the Prescribing Information (Viela Bio, 2020), Uplizna is contraindicated in persons with a history of a life-threatening infusion reaction to inebilizumab, active hepatitis B infection, and active or untreated latent tuberculosis (TB). In addition, the following are the warnings and precautions included for the associated FDA-approved recommendations:

• Infusion reactions: Administer premedications prior to infusion. Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue Uplizna if a life-threatening or disabling infusion reaction occurs.
• Infections: Delay administration in persons with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.
• Immunoglobulin levels: Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with Uplizna until B-cell repletion. Consider discontinuing Uplizna if person develops a serious opportunistic infection or recurrent infections if immunoglobulin levels indicate immune compromise.
• Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping Uplizna.

The most common adverse reactions (at least 10% of patients treated with Uplizna and greater than placebo) were urinary tract infection and arthralgia (Viela Bio, 2020).

Concomitant usage of Uplizna with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when co-administering immunosuppressive therapies with Uplizna (Viela Bio, 2020).

Safety and effectiveness in pediatric have not been established. Clinical studies of Uplizna did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients (Viela Bio, 2020).

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96365 - 96368	Intravenous infusion administration
HCPCS codes covered if selection criteria are met:
J1823	Injection, inebilizumab-cdon, 1 mg
ICD-10 codes covered if selection criteria are met:
G36.0	Neuromyelitis optica [Devic]

The above policy is based on the following references: