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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:061
Effective Date: 09/11/2020
Original Policy Date:11/11/2008
Last Review Date:09/08/2020
Date Published to Web: 10/11/2018
Subject:
Eculizumab (Soliris) and Ravulizumab-cwvz (Ultomiris)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

__________________________________________________________________________________________________________________________

On March 16, 2007, eculizumab (Soliris) was FDA approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare hematopoietic stem-cell disorder caused by a somatic mutation in a gene known as phosphatidylinositol glycan class A (PIGA). The condition can arise de novo or in the setting of acquired aplastic anemia. Clinical presentation primarily includes hemolytic anemia (often requiring transfusions), hemoglobinuria, thrombosis, severe fatigue, abdominal pain, esophageal spasm, and subsequent shortness of breath, thus leading to an impaired quality of life. Thrombosis, which is the leading cause of death from PNH, most commonly occurs in abdominal and cerebral veins. Current therapeutic options include supportive care, bone marrow transplantation, and monoclonal antibody therapy with the terminal complement inhibitor eculizumab (Soliris). According to the FDA, eculizumab (Soliris) has been classified as an orphan drug. It is a new molecular entity and the first and only product in its class, in addition to the only FDA-approved agent for the treatment of PNH. On September 23, 2011, eculizumab (Soliris) was FDA approved for the treatment of atypical hemolytic uremic syndrome (aHUS), a rare pediatric blood disorder, to inhibit complement-mediated thrombotic microangiopathy. The effectiveness of eculizumab (Soliris) in aHUS is based on the effects on thrombotic microangiopathy (TMA) and renal function.
    Eculizumab (Soliris) is a recombinant, humanized, monoclonal antibody which specifically binds to the complement protein C5 with high affinity, inhibiting its cleavage to C5a and C5b, thus preventing the generation of the terminal complement complex C5b-9. Eculizumab (Soliris) inhibits complement-mediated hemolysis, which is the underlying cause of PNH symptoms. By reducing red blood cell destruction, or hemolysis, treatment with eculizumab (Soliris) improves anemia, fatigue, and other symptoms associated with PNH, helping patients enjoy a better quality of life. In clinical trials, patients also experienced fewer blood clots with eculizumab (Soliris) treatment as compared to the their pre-treatment state.
      Two pivotal clinical trials assessed the safety and efficacy of eculizumab (Soliris) in PNH patients, along with one meta-analysis:
        • Study 1 - A multicenter, double-blind, placebo-controlled, phase 3 trial that included 87 paroxysmal nocturnal hemoglobinuria (PNH) patients aged 18 years or older. Patients were randomized to receive the FDA-approved and recommended eculizumab dosage regimen (43 patients) or placebo (44 patients) for 26 weeks. In the eculizumab group, 49% of the patients maintained stable hemoglobin levels, vs. 0% in the placebo group.. The number of packed red cells transfused in the treatment group (131 units) was significantly less (73% reduction in units of blood transfused) than that seen in the placebo group (482 units). Hemolysis was also significantly reduced in the treatment group as compared to the placebo group. Patients on eculizumab (Soliris) reported less fatigue and better health-related quality of life compared to the patients taking the placebo. Common side effects included headache (similar incidence to placebo), runny nose, and nausea.
        • Study 2 - A multicenter, open-label, single-arm, phase 3 trial that included 97 paroxysmal nocturnal hemoglobinuria (PNH) patients aged 18 years or older. All patients received the FDA-approved and recommended eculizumab dosage regimen for 52 weeks. In 6 patients, the dosing interval was reduced to 12 days instead of 14 days. There were a total of 277 infections identified throughout the study duration. No deaths occurred, with all patients successfully completing the study. At 52 weeks, only 1 patient experienced a pulmonary embolism and 1 patient experienced a deep vein thrombosis. The reduction in hemolysis, as compared to baseline, resulted in a reduction of blood transfusions and improvement in fatigue and health-related quality of life, similar to the results from Study 1. In addition, eculizumab (Soliris) was found to have a similar safety profile to Study 1 and was well tolerated over a period of 1 year.
        • Study 3 - A meta-analysis of 3 previously conducted trials was conducted, including 195 paroxysmal nocturnal hemoglobinuria (PNH) patients aged 18 years or older. The objective of this study was to evaluate the use of eculizumab in reducing the rates of thromboembolism in patients with PNH. The incidence of thromboembolism decreased from 124 events to 3 events after initiation of eculizumab therapy.
      A total of 3 cases of meningococcal sepsis have been observed during clinical trials. Two cases were observed in patients with PNH who had previously received a meningococcal vaccine, while the third case occurred in a patient without a diagnosis of PNH, who had not previously received the meningococcal vaccine.
        Eculizumab (Soliris)’ safety and effectiveness were established in two single-arm trials in 37 adults and adolescent patients with aHUS and one retrospective study in 19 pediatric patients and 11 adult patients with aHUS assessed the efficacy of eculizumab (Soliris) Soliris for aHUS.
          • Patients treated with eculizumab (Soliris) in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients with aHUS that did not respond to plasma therapy. Patients treated with eculizumab (Soliris) also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.
          • Three single-arm studies [(two prospective (aHUS Studies 1 and 2) and one retrospective (aHUS Study 3)] evaluated the safety and efficacy of eculizumab (Soliris) for the treatment of aHUS. Patients with aHUS received meningococcal vaccination prior to receipt of Soliris or received prophylactic treatment with antibiotics until 2 weeks after vaccination. In all studies, the dose of eculizumab (Soliris) in adult and adolescent patients was 900 mg every 7 ± 2 days for 4 weeks, followed by 1200 mg 7 ± 2 days later, then 1200 mg every 14 ± 2 days thereafter. The dosage regimen for pediatric patients weighing less than 40 kg enrolled in aHUS Study 3 was based on body weight. Efficacy evaluations were based on thrombotic microangiopathy (TMA) endpoints.
        The most common side effects seen in patients treated with eculizumab (Soliris) for aHUS included high blood pressure (hypertension), diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and a decrease in white blood cells (leukopenia).

        On April 30, 2014, the FDA approved package labeling was updated to include additional Dosage and Administration information. The eculizumab (Soliris) admixture should be administered by intravenous infusion over 35 minutes in adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump.

        On October 23, 2017, the FDA approved eculizumab (Soliris) for the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are antiacetylcholine receptor (AchR) antibody positive.

        The efficacy of eculizumab (Soliris) for the treatment of gMG was established in gMG Study 1 (NCT01997229), a 26-week randomized, double-blind, parallel-group, placebo-controlled, multicenter trial. A total of 62 patients were randomized to receive eculizumab (Soliris) treatment and 63 were randomized to receive placebo. Baseline characteristics were similar between treatment groups, including age at diagnosis (38 years in each group), gender [66% female (eculizumab) versus 65% female (placebo)], and duration of gMG [9.9 (eculizumab) versus 9.2 (placebo) years]. Over 95% of patients in each group were receiving acetylcholinesterase (AchE) inhibitors, and 98% were receiving immuno-suppressant therapies (ISTs). Approximately 50% of each group had been previously treated with at least 3 ISTs.

        The primary efficacy endpoint for gMG Study 1 was a comparison of the change from baseline between treatment groups in the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) total score at Week 26. key secondary endpoint in gMG Study 1 was the change from baseline in the Quantitative Myasthenia Gravis (QMG) total score at Week 26.

        In gMG Study 1, a clinical response was defined in the MG-ADL total score as at least a 3-point improvement and in QMG total score as at least a 5-point improvement. The proportion of clinical responders at Week 26 with no rescue therapy was statistically significantly higher for eculizumab (Soliris) compared to placebo for both measures. For both endpoints, and also at higher response thresholds (≥4-, 5-, 6-, 7-, or 8-point improvement on MG-ADL, and ≥6-, 7-, 8-, 9-, or 10-point improvement on QMG), the proportion of clinical responders was consistently greater for eculizumab (Soliris) compared to placebo. Available data suggest that clinical response is usually achieved by 12 weeks of eculizumab (Soliris) treatment.

        In June 2019, the FDA approved eculizumab (Soliris) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

        The efficacy of Soliris for the treatment of NMOSD was established in NMOSD Study 1 (NCT01892345), a randomized, double-blind, placebo-controlled trial that enrolled 143 patients with NMOSD who were anti-AQP4 antibody positive and met the following criteria at screening: 1. History of at least 2 relapses in last 12 months or 3 relapses in the last 24 months, with at least 1 relapse in the 12 months prior to screening, 2. Expanded Disability Status Scale (EDSS) score ≤ 7 (consistent with the presence of at least limited ambulation with aid), 3. If on immunosuppressive therapy (IST), on a stable dose regimen. 4. The use of concurrent corticosteroids was limited to 20 mg per day or less, 5. Patients were excluded if they had been treated with rituximab or mitoxantrone within 3 months or with IVIg within 3 weeks prior to screening.

        A total of 96 patients were randomized to receive Soliris treatment and 47 were randomized to receive placebo. The baseline demographic and disease characteristics were balanced between treatment groups. During the treatment phase of the trial, 76% percent of patients received concomitant IST, including chronic corticosteroids; 24% of patients did not receive concomitant IST or chronic corticosteroids during the treatment phase of the trial. Soliris was administered according to the recommended dosage regimen. The primary endpoint for NMOSD Study 1 was the time to the first adjudicated on-trial relapse. The time to the first adjudicated on-trial relapse was significantly longer in Soliris-treated patients compared to placebo-treated patients (relative risk reduction 94%; hazard ratio 0.058; p < 0.0001).

        Soliris-treated patients experienced similar improvement in time to first adjudicated on-trial relapse with or without concomitant treatment. Soliris-treated patients had a 96% relative reduction in the adjudicated on-trial annualized relapse rate (ARR) compared to patients on placebo. Compared to placebo-treated patients, Soliris-treated patients had reduced annualized rates of hospitalizations (0.04 for Soliris versus 0.31 for placebo), of corticosteroid administrations to treat acute relapses (0.07 for Soliris versus 0.42 for placebo), and of plasma exchange treatments (0.02 for Soliris versus 0.19 for placebo).

        On December 21, 2018 The U.S. Food and Drug Administration today approved ravulizumab-cwvz (Ultomiris) injection for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

        Ravulizumab-cwvz (Ultomiris) is a humanized monoclonal antibody to complement component C5, engineered from eculizumab (Soliris). It is identical to eculizumab (Soliris) but with a longer half-life. Ravulizumab-cwvz (Ultomiris) is a terminal complement inhibitor that binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b9. Ravulizumab-cwvz (Ultomiris) inhibits terminal complement-mediated intravascular hemolysis in patients with PNH.

        The safety and efficacy of ravulizumab-cwvz (Ultomiris) in patients with PNH was assessed in two open label, randomized, active-controlled, non-inferiority Phase 3 studies: PNH Study 301 and PNH Study 302. Study 301 enrolled patients with PNH who were complement inhibitor naïve and had active hemolysis. Study 302 enrolled patients with PNH who were clinically stable after having been treated with eculizumab (Soliris) for at least the past 6 months.

        In both studies, ravulizumab-cwvz (Ultomiris) was dosed intravenously in accordance with the weight based. Eculizumab (Soliris) was administered on Days 1, 8, 15, and 22, followed by maintenance treatment with 900 mg of eculizumab (Soliris) on Day 29 and every 2 weeks (q2w) thereafter for a total of 26 weeks of treatment, according to the approved dosing regimen of eculizumab (Soliris) which was the standard-of-care for PNH at the time of studies.
        The results of Study 301 demonstrated that ravulizumab-cwvz (Ultomiris) was non-inferior to eculizumab (Soliris) – patients did not receive a transfusion and had similar incidence of hemolysis measured by the normalization of LDH(lactate dehydrogenase) levels in patients’ blood. The results of Study 302 demonstrated non-inferiority to eculizumab (Soliris)
        based on several clinical measures including hemolysis and avoiding transfusion.

          • In Study 301, efficacy was established based upon transfusion avoidance and reduction of hemolysis as directly measured by normalization of LDH levels. Transfusion avoidance was defined as patients who did not receive a transfusion and did not meet the protocol specified guidelines for transfusion from baseline up to Day 183. Transfusion avoidance was seen in 73.6% and 66.1% of patients who received ravulizumab-cwvz (Ultomiris) and eculizumab (Soliris) , respectively (rate difference 6.8; 95% CI: -4.66, 18.14) and LDH normalization was seen in 53.6% and 49.4% of patients who received ravulizumab-cwvz (Ultomiris) and eculizumab (Soliris) , respectively (odds ratio 1.19; 95% CI: 0.80. 1.77). Supportive efficacy data included LDH percent change, breakthrough hemolysis and proportion of patients with stabilized hemoglobin levels. Non-inferiority of ravulizumab-cwvz (Ultomiris) to eculizumab (Soliris) was demonstrated across the endpoints.
          • In Study 302, efficacy was established based on hemolysis as measured by LDH percent change from baseline to Day 183. LDH percent change was -0.82% and 8.4% for patients who received ravulizumab-cwvz (Ultomiris) and eculizumab (Soliris) , respectively (rate difference 9.2; 95% CI: -0.42, 18.8). Supportive efficacy data included transfusion avoidance, proportion of patients with stabilized hemoglobin and proportion of patients with breakthrough hemolysis. Non-inferiority of ravulizumab-cwvz (Ultomiris) to eculizumab (Soliris) was demonstrated across all endpoints.
          • Patients were vaccinated against meningococcal infection prior to or at the time of initiating treatment with ravulizumab-cwvz (Ultomiris) or eculizumab (Soliris) , or received prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination. Prophylactic treatment with appropriate antibiotics beyond 2 weeks after vaccination was at the discretion of the provider.
        In October 2019, ravulizumab-cwvz (Ultomiris) was approved for the treatment of adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). The efficacy of ravulizumab-cwvz (Ultomiris) in patients with aHUS was assessed in 2 open-label, single-arm studies. Study ALXN1210-aHUS-311 enrolled adult patients who displayed signs of TMA.
          • The adult study, ALXN1210-aHUS-311, was conducted in patients who were naïve to complement inhibitor treatment prior to study entry. The study consisted of a 26-week Initial Evaluation Period and patients were allowed to enter an extension period for up to 4.5 years. A total of 56 patients with aHUS were evaluated for efficacy. The efficacy evaluation was based on Complete TMA Response during the 26-week Initial Evaluation Period, as evidenced by normalization of hematological parameters (platelet count and LDH) and ≥ 25% improvement in serum creatinine from baseline. Patients had to meet each Complete TMA Response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. Complete TMA Response was observed in 30 of the 56 patients (54%) during the 26-week Initial Evaluation Period.
          • The Pediatric Study, ALXN1210-aHUS-312, is a 26-week ongoing, multicenter, single-arm study conducted in 16 pediatric patients. A total of 14 eculizumab-naïve patients with documented diagnosis of aHUS were enrolled and included in this interim analysis. Efficacy evaluation was based upon Complete TMA Response during the 26-week Initial Evaluation Period, as evidenced by normalization of hematological parameters (platelet count and LDH) and ≥ 25% improvement in serum creatinine from baseline. Patients had to meet all Complete TMA Response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. Complete TMA Response was observed in 10 of the 14 patients (71%) during the 26-week Initial Evaluation Period.

        [INFORMATIONAL NOTES:
        FDA labeled package insert on Eculizumab (Soliris) includes the following black box warning:
        Eculizumab (Soliris) increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Cases of meningococcal sepsis have been reported in those with PNH who were previously vaccinated, in addition to those without PNH, who were previously non-vaccinated.

          • All patients without a history of prior meningococcal vaccination must receive the meningococcal vaccine at least 2 weeks prior to receiving the first dose of eculizumab (Soliris), and should be re-vaccinated according to current medical guidelines for vaccine use.
          • Patients should be closely monitored for early signs and symptoms of meningococcal infections and evaluated immediately if an infection is suspected. Patients should receive supportive therapy and antibiotics if necessary. Physicians should strongly consider discontinuing Solis eculizumab (Soliris)therapy during the treatment of serious meningococcal infections.
          • Eculizumab (Soliris) is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Eculizumab (Soliris)REMS, prescribers must enroll in the program.
        FDA labeled package insert on ravulizumab-cwvz (Ultomiris) includes the following black box warning:
          • Life-threatening meningococcal infections/sepsis have occurred in patients treated with ravulizumab-cwvz (Ultomiris) . Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early
          • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
          • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Ravulizumab-cwvz (Ultomiris) , unless the risks of delaying ravulizumab-cwvz (Ultomiris) therapy outweigh the risk of developing a meningococcal infection
          • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
          • Ravulizumab-cwvz (Ultomiris) is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).]

        Policy:
        (NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

        The requirements of the Horizon BCBSNJ Eculizumab (Soliris) and Ravulizumab-cwvz (Ultomiris) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

        1. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.

        2. Prior to starting therapy with Eculizumab (Soliris) or Ravulizumab-cwvz (Ultomiris), the following criteria must be met:

          • Member must be immunized with a meningococcal vaccine at least 2 weeks prior to administration of the first dose of eculizumab (Soliris) or ravulizumab-cwvz (Ultomiris) and revaccinated according to current medical guidelines for vaccine use, unless the risks of delaying therapy outweigh the risks of developing a meningococcal infection
            • If urgent therapy is indicated in an unvaccinated patient, administer meningococcal vaccine as soon as possible and provide patient with 2 weeks of antibacterial drug prophylaxis.
          • Member must not have unresolved serious Neisseria meningitidis infection
          • Prescribing physician must be enrolled in the Risk Evaluation and Mitigation Strategy (REMS) program

        3. Eculizumab (Soliris) and Ravulizumab-cwvz (Ultomiris) are medically necessary for the following FDA-approved indications:
          • Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adult members (18 years or older) to reduce hemolysis with all of the following:
              • Diagnosis must be accompanied by detection of PNH clones by flow cytometry diagnostic test demonstrating at least 10% [for eculizumab (Soliris)] or 5% [for ravulizumab-cwvz (Ultomiris)] PNH type III red cells OR greater than 50% of glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient poly-morphonuclear cells (PMNs) (documentation of medical records required); AND
              • Documented baseline values of one or more of the following: serum lactate dehydrogenase (LDH), hemoglobin level, and packed RBC transfusion requirement (documentation of medical records required); AND
              • Patient has one of the following indications for therapy (documentation of medical records required):
                  • Presence of a thrombotic event
                  • Presence of organ damage secondary to chronic hemolysis
                  • Patient is pregnant and potential benefit outweighs potential fetal risk
                  • Patient is transfusion dependent (i.e has at least 1 transfusion in the 24 months prior to therapy initiation due to documented hemoglobin less than 7 g/dL in those without anemic symptoms or less than 9 g/dL in those with symptoms from anemia)
                  • Patient has high LDH activity (defined as ≥1.5 x ULN) with clinical symptoms [fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 g/dl), history of MAVE (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH]; AND
              • If the request is for eculizumab (Soliris), the requested drug will not be used in combination with ravulizumab-cwvz (Ultomiris) AND member has trial and failure, contraindication or allergy to Ultomiris (ravulizumab-cwvz)
              • If the request is for ravulizumab-cwvz (Ultomiris), the requested drug will not be used in combination with eculizumab (Soliris)
        [INFORMATIONAL NOTE: Soliris and Ultomiris are specifically FDA-approved for use in patients with paroxysmal nocturnal hemoglobinuria (PNH). The P&T Committee at Horizon Blue Cross Blue Shield of New Jersey subjects each prescription drug being considered for formulary placement to a rigorous clinical analysis. Based on the decrease in administration burden for both members and physicians, the clinical and effective analysis, the P&T Committee recommends the placement of Ultomiris as preferred.]
          • Treatment of atypical hemolytic uremic syndrome (aHUS), a rare pediatric blood disorder, to inhibit complement-mediated thrombotic microangiopathy in pediatrics (> 1 month old for ravulizumab-cwvz (Ultomiris) and > 2 months old for Eculizumab (Soliris) and adults with all of the following:
              • Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS), typical HUS, and infection related HUS has been ruled out; AND
              • Other causes have been ruled out such as coexisting diseases or conditions (e.g. bone marrow transplantation, solid organ transplantation, malignancy, autoimmune disorder, drug-induced, malignant hypertension, HIV infection, etc.), Streptococcus pneumoniae or Influenza A (H1N1) infection, or cobalamin deficiency; AND
              • Diagnosis of thrombocytopenitc purpura (TTP) has been ruled out, i.e. patient has normal ADAMTS 13 activity; AND
              • Baseline values of the following: serum lactate dehydrogenase (LDH), serum creatinine/eGFR, platelet count, and plasma exchange/infusion requirement (documentation of medical records required) AND
              • If the request is for eculizumab (Soliris), the requested drug will not be used in combination with ravulizumab-cwvz (Ultomiris) AND member has trial and failure, contraindication or allergy to Ultomiris (ravulizumab-cwvz)
              • If the request is for ravulizumab-cwvz (Ultomiris), the requested drug will not be used in combination with eculizumab (Soliris)
          • Treatment of generalized myasthenia gravis (gMG) in adults patients who are anti-acetylcholine receptor (AchR) antibody positive with all of the following [Eculizumab (Soliris) ONLY)] (documentation of medical records required):
              • Patient has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of Class II to IV disease; AND
              • Physician has assessed the baseline Quantitative Myasthenia Gravis (QMG) score; AND
              • Patient has a MG-Activities of Daily Living (MG-ADL) total score of ≥6; AND
              • Patient has failed treatment over at least 1 year with at least 2 immunosuppressive therapies (e.g. azathioprine, cyclosporine, mycophenolate), or has failed at least 1 immunosuppressive therapy and required chronic plasmapheresis or plasma exchange (PE) or intravenous immunoglobulin (IVIG)
          · Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive with all of the following [Eculizumab (Soliris) ONLY)]:
              • Patient has history of at least 2 relapses in last 12 months or 3 relapses in the last 24 months, with at least 1 relapse in the 12 months prior to screening (documentation of medical records required); AND
              • Expanded Disability Status Scale (EDSS) score ≤ 7 (consistent with the presence of at least limited ambulation with aid) (documentation of medical records required); AND
              • If on immunosuppressive therapy (IST), patient is on a stable dose regimen. Concurrent corticosteroids are limited to 20 mg per day or less; AND
              • Patient cannot have been treated with rituximab or mitoxantrone within 3 months or with IVIg within 3 weeks; AND
              • Patient will not be using in combination with inebilizumab-cdon (Uplizna) or satralizumab-mwge (Enspryng)
          [INFORMATIONAL NOTE: As per the FDA-approved package insert, eculizumab (Soliris) therapy should not be initiated in patients with unresolved serious Neisseria meningitides infection, as well as in patients who are not currently vaccinated against Neisseria meningitidis. Due to the fact that eculizumab (Soliris) blocks terminal complement, patients may have increased susceptibility to infections. Thus, it is advised to use caution when administering therapy to patients with evidence of any systemic infection. Children treated with eculizumab (Soliris) may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza type b (Hib) infections according to ACIP guidelines.

          In June 2010, Alexion Pharmaceuticals instituted an FDA approved Risk Evaluation and Mitigation Strategies (REMS) program. The FDA determined that eculizumab (Soliris) poses a serious and significant public health concern due to increased risk of meningococcal infection and hemolysis post-discontinuation. The REMS program will include a patient Medication Guide, Elements to Assure Safe Use ensuring that prescribing physicians are identified and specially certified and educated on eculizumab (Soliris) use and patients are monitored for adverse events, and a timetable of submission of data collected to the FDA for analysis.

          As per the FDA-approved package insert, eculizumab (Soliris) therapy should not be initiated in patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

          As per the FDA-approved package insert, ravulizumab-cwvz (Ultomiris) therapy should not be initiated in patients with unresolved serious Neisseria meningitides infection, as well as in patients who are not currently vaccinated against Neisseria meningitides

          Due to the risk of meningococcal infections, ravulizumab-cwvz (Ultomiris) is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).]
        4. When eculizumab (Soliris) is medically necessary, therapy will be approved at the following FDA recommended doses for an initial duration of 6 months:
          a. Paroxysmal Nocturnal Hemoglobinuria (PNH)
            i. 600 mg IV every 7 days for the first 4 weeks, followed by 900 mg IV for the fifth dose 7 days later, then 900 mg IV every 14 days thereafter
          b. Atypical Hemolytic Uremic Syndrome (aHUS)
              i. In adult members 18 years and older
                  1. 900 mg IV every 7 days for the first 4 weeks, followed by
                  2. 1200 mg IV for the fifth dose 7 days later, then
                  3. 1200 mg IV every 14 days thereafter
              ii. In pediatric members less than 18 years old with weight based dosing:
                  1. 40 kg and over
                      a. 900 mg IV every 7 days for the first 4 weeks, followed by
                      b. 1200 mg IV for the fifth dose 7 days later, then
                      c. 1200 mg IV every 14 days thereafter
                  2. 30 kg to less than 40 kg
                      a. 600 mg IV every 7 days for the first 2 weeks, followed by
                      b. 900 mg IV for the third dose 7 days later, then
                      c. 900 mg IV every 14 days thereafter
                  3. 20 kg to less than 30 kg
                      a. 600 mg IV every 7 days for the first 2 weeks, followed by
                      b. 600 mg IV for the third dose 7 days later, then
                      c. 600 mg IV every 14 days thereafter
                  4. 10 kg to less than 20 kg
                      a. 600 mg IV every 7 days for the first week, followed by
                      b. 300 mg IV for the second dose 7 days after, then
                      c. 300 mg IV every 14 days thereafter
                  5. 5 kg to less than 10 kg
                      a. 300 mg IV every 7 days for the first week, followed by
                      b. 300 mg IV for the second dose 7 days after, then
                      c. 300 mg IV every 21 days thereafter
          c. Generalized Myasthenia Gravis (gMG)
              i. Loading dose:
                  - 900 mg intravenously every 7 days for the first 4 weeks, followed by 1,200 mg intravenously for the fifth dose 7 days later
              ii. Maintenance dose:
                  - 1200 mg intravenously every 14 days
          d. Neuromyelitis Optica Spectrum Disorder (NMOSD)
              i. Loading dose:
                  - 900 mg intravenously every 7 days for the first 4 weeks, followed by 1,200 mg intravenously for the fifth dose 7 days later
              ii. Maintenance dose:
                  - 1200 mg intravenously every 14 days

          [INFORMATIONAL NOTE: As per package insert:
          Dose Adjustment for aHUS (adult and pediatric patients) and gMG (adult patients) in case of Plasmapheresis, Plasma Exchange or Fresh Frozen Plasma Infusion
          Type of Plasma Exchange
          Most Recent Soliris Dose
          Supplemental Soliris With Each Plasma Intervention
          Timing of Supplemental Soliris Dose
          Plasmapheresis or plasma exchange (PE)
          300 mg
          300 mg per each plasmapheresis or PE
          Within 60 minutes after each plasmapheresis or PE
          ≥ 600 mg
          600 mg per each plasmapheresis or PE
          Fresh frozen plamsa infusion (FFP)
          ≥ 300 mg
          300 mg per each infusion of FFP
          60 minutes prior to each infusion of FFP
          • Eculizumab (Soliris) should be administered at the recommended dosage regimen time points, or within two days of these time points, as serum LDH levels can fluctuate based on dosing and inconsistent eculizumab levels. In clinical studies, 6 patients achieved a reduction in LDH levels only after a decrease in the eculizumab (Soliris) dosing interval from 14 to 12 days. LDH levels increase during hemolysis and thus, may assist in monitoring the effects of eculizumab (Soliris), including the response to discontinuation of therapy.
          • Eculizumab (Soliris) should be diluted to a concentration of 5 mg/ml and administered as an intravenous infusion over 35 minutes in adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump. It should not be administered as an intravenous push or as a bolus injection. It is also recommended to monitor the patient for 1 hour post-infusion for signs and symptoms of infusion-related reactions. If an adverse reaction does occur during administration of eculizumab (Soliris), the infusion may be slowed or stopped at the discretion of the physician.
          • Eculizumab (Soliris) is supplied as 300 mg single-use vials, each containing 30 mL of 10 mg/mL sterile, preservative-free solution.]
        5. When ravulizumab-cwvz (Ultomiris) ) is medically necessary, therapy will be approved at the following FDA recommended weight-based doses for an initial duration of 6 months:
          · Paroxysmal Nocturnal Hemoglobinuria (PNH): administer the loading dose, then 2 weeks later, begin maintenance dose
              • Greater than or equal to 40 kg less than 60 kg
                  § Loading dose (mg): 2,400
                  § Maintenance dose ( mg): 3,000 every 8 weeks
              • Greater than or equal to 60 kg to less than 100 kg
                  § Loading dose (mg): 2,700
                  § Maintenance dose ( mg): 3,300 every 8 weeks
              • Greater than or equal to 100 kg
                  § Loading dose (mg): 3,000
                  § Maintenance dose ( mg): 3,600 every 8 weeks
          • Atypical Hemolytic Uremic Syndrome (aHUS): administer the loading dose, then 2 weeks later, begin maintenance dose
              • Greater than or equal to 5 kg less than 10 kg
                  • Loading dose (mg): 600
                  • Maintenance dose ( mg): 300 every 4 weeks
              • Greater than or equal to 10 kg to less than 20 kg
                  • Loading dose (mg): 600
                  • Maintenance dose (mg): 600 every 4 weeks
              • Greater than or equal to 20 kg to less than 30 kg
                  • Loading dose (mg): 900
                  • Maintenance dose (mg): 2,100 every 8 weeks
              • Greater than or equal to 30 kg to less than 40 kg
                  • Loading dose (mg): 1,200
                  • Maintenance dose (mg): 2,700 every 8 weeks
              • Greater than or equal to 40 kg to less than 60 kg
                  • Loading dose (mg): 2,400
                  • Maintenance dose (mg): 3,000 every 8 weeks
              • Greater than or equal to 60 kg to less than 100 kg
                  • Loading dose (mg): 2,700
                  • Maintenance dose (mg): 3,300 every 8 weeks
              • Greater than or equal to 100 kg
                  • Loading dose (mg): 3,000
                  • Maintenance dose (mg): 3,600 every 8 weeks
          [INFORMATIONAL NOTE: The recommended dosing regimen for adult patients (≥ 18 years of age) with PNH consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Starting 2 weeks after the loading dose administration, begin maintenance doses at a once every 8-week interval. The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab-cwvz (Ultomiris) but the subsequent dose should be administered according to the original schedule. The recommended dosing regimen in adult and pediatric patients one month of age and older with aHUS weighing 5 kg or greater, consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Starting 2 weeks after the loading dose administration, begin maintenance doses once every 8 weeks or every 4 weeks (depending on body weight). The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab-cwvz (Ultomiris); but the subsequent doses should be administered according to the original schedule. For patients switching from eculizumab (Soliris) to ravulizumab-cwvz (Ultomiris) , administer the loading dose of ravulizumab-cwvz (Ultomiris) 2 weeks after the last eculizumab (Soliris) infusion, and then administer maintenance doses once every 8 weeks, starting 2 weeks after loading dose administration]

          6. At the end of the initial 6 month period, eculizumab (Soliris) and ravulizumab-cwvz (Ultomiris) will be continued and approved annually, subject to the following medical necessity criteria:

            • Prescriber is enrolled in the Risk Evaluation and Mitigation Strategy (REMS) program; AND
            • There is absence of unacceptable toxicity from the drug (e.g.: serious meningococcal infections (septicemia and/or meningitis), infusion reactions, serious systemic infections, intravascular hemolysis) AND
            • Approval for continued use will be granted for treatment of PNH if the member responds to therapy as demonstrated by stabilization of disease or improvement in any of the following symptoms:
              • Reduction in chronic hemolysis
              • Reduction in serum LDH levels, as compared to pre-treatment levels
              • Improvement in fatigue
              • Stabilization/improvement of hemoglobin levels compared to pre-treatment levels
              • Improvement in anemia, along with a reduction in the number of blood transfusions required compared to pre-treatment state
              • Lower incidence of thrombosis as compared to pre-treatment state
            • Approval for continued use will be granted for treatment of aHUS if the member responds to therapy as demonstrated by stabilization of disease or improvement in any of the following:
              • Clinical signs and symptoms of TMA (mental status, seizures, angina, dyspnea, or thrombosis)
              • Reduction in serum LDH levels, as compared to pre-treatment levels
              • Reduction in serum creatinine/improvement in estimated glomerular filtration rate (eGFR), as compared to pre-treatment levels
              • Increase in platelet counts, as compared to pre-treatment levels
              • Decrease in plasma exchange/infusion requirement compared to pre-treatment state
            • Approval for continued use will be granted for treatment of gMC if the member responds to therapy as demonstrated by stabilization of disease or improvement in any of the following symptoms [Eculizumab (Soliris) ONLY]:
              • Improvement of at least 3 points in the MG-ADL score, as compared to pre-treatment levels
              • Improvements of at least 5 points in the Quantitative myasthenia Gravis (QMG) score, as compared to pretreatment levels
            • Approval for continued use will be granted for treatment of NMSOD if the member responds to therapy as demonstrated by stabilization of disease or improvement in any of the following symptoms [Eculizumab (Soliris) ONLY]:
              • Reduction in relapses
              • Reduction of hospitalizations
              • Reduction of corticosteroid administrations to treat acute relapses
              • Reduction of plasma exchange treatments

            [INFORMATIONAL NOTE: As per package inserts, patients who discontinue eculizumab (Soliris) for the treatment of PNH may be at an increased risk for serious hemolysis. Upon discontinuation, it is recommended to monitor patients for a minimum of 8 weeks to detect signs of hemolytic activity or other reactions. Serious hemolysis can be identified by serum LDH levels that are greater than pre-treatment levels, in addition to the following parameters:
            • A hemoglobin level of < 5 gm/dL or a decrease of > 4 gm/dL in one week or less
            • Greater than 25% absolute decrease in PNH clone size (in absence of dilution due to transfusion) in one week or less
            • Angina
            • Change in mental status
            • A 50% increase in serum creatinine level
            • Thrombosis.

            Patients who discontinue eculizumab (Soliris) for the treatment of aHUS may be at an increased risk for thrombotic microangiopathy (TMA) complications. Monitor patients with aHUS for signs and symptoms of TMA complications for at least 12 weeks. Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during eculizumab (Soliris) treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during eculizumab (Soliris) treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during eculizumab (Soliris)treatment.

            Early signs of thrombotic microangiopathy (TMA) include a decrease in platelet count, and increases in serum LDH and creatinine levels. Follow patients for signs of TMA by monitoring serial platelet counts, serum LDH, and creatinine during Soliris therapy and following discontinuation of eculizumab (Soliris).

            If TMA complications occur after eculizumab (Soliris)discontinuation, consider reinstitution of eculizumab (Soliris) treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

            As per FDA approved package insert after discontinuing treatment with ravulizumab-cwvz (Ultomiris) , closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ravulizumab-cwvz (Ultomiris) for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ravulizumab-cwvz (Ultomiris).]

          6. Other uses of eculizumab (Soliris) and ravulizumab-cwvz (Ultomiris), including but not limited to melanoma, cardiac transplantation, complement-mediated injury in kidney transplant, CD59 deficiency, catastrophic antiphospholipid antibody syndrome, Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis, generalized myasthenia gravis, macular edema, and macular degeneration are considered investigational.
            Medicare Coverage:
            There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.

            **Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.

            Medicaid Coverage:
            For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

            ________________________________________________________________________________________

            Horizon BCBSNJ Medical Policy Development Process:

            This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

            ___________________________________________________________________________________________________________________________

            Index:
            Eculizumab (Soliris)
            Soliris (Eculizumab)
            Ravulizumab-cwvz (Ultomiris)
            Ultomiris (Ravulizumab-cwvz)

            References:
            1. Soliris (eculizumab) [package insert]. Alexion Pharmaceuticals, Inc. New Haven, CT. June 2019.

            2. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106:3699-3708.

            3. U.S. Food and Drug Administration: FDA News. FDA Approves First-of-its-Kind Drug to Treat Rare Blood Disorder. March 2007. [Available at: http://www.fda.gov/bbs/topics/news/2007/new01589.html].

            4. Brodsky, RA. Narrative Review: Paroxysmal Nocturnal Hemoglobinuria: The Physiology of Complement-Related Hemolytic Anemia. Ann Intern Med 2008; 148:587-595.

            5. Antonioll, E, Brodsky, RA, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood February 2008; 111 (4):1840-1847.

            6. Hillmen, P, Muus, P, Risitano, AM, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood December 2007: 110 (12): 4123-4128.

            7. Hillmen P, Young NS, Schuber J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006 Sep 21;355(12):1233-43.

            8. U.S. Food and Drug Administration: Drug Safety. BLA 125166 Soliris® (eculizumab) Recombinant Humanized Monoclonal Antibody REMS. April 2010. [Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM217725.pdf]

            9. LockingtonD, Imrie F, Gillen J, et al. Visual improvement in established central retinal vein occlusion with long-standing macular edema following systemic eculizumab treatment. Can I Ophthalmol. 2010 Dec;45(6):649.

            10. Zuber J, Le Quintrec M, Sberro R, et al. New insights into póstrenla transplant hemolytic uremia symdrome. Nat Rev Nephrol. 2011 Jan;7(1):23-25

            11. Manganoni AM, Pavoni L, Facchetti F, et al. Melanoma in a patient in treatment with eculizumab. Ann Hematol. 2011 April 5 [Epub ahead of print]

            12. U.S. Food and Drug Administration: FDA News Release. FDA approves Soliris for rare pediatric blood disorder. Sept 2011. [Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272990.htm]

            13. Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology. 2014 Mar;121(3):693-701.

            14. Howard J, Utsugisawa K, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (REGAIN): a phase 4, randomized, double-blind, placebo-controlled, multicentre study. The Lancet Neurology. 2017 October; 4422(17) 30369-1.

            15. Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis (REGAIN study). ClinicalTrials.gov. Accessed October 2017. Available at: https://clinicaltrials.gov/show/NCT01997229.

            16. Myasthenia Gravis: A manual for the healthcare Provider. Myasthenia Gravis Foundation of America. Accessed October 2017. Available at: http://www.myasthenia.org/HealthProfessionals.

            17. Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016;6(2): 19-27.

            18. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis-Executive Summary. Neurology. 2016 Jul 26; 87(4): 419-25.

            19. Howard JF. REGAIN: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG). Presented at the 14th International Congress on Neuromuscular Diseases (ICNMD), Toronto, July 7, 2016.

            20. Ultomiris (ravulizumab-cwvz) [package insert]. Alexion Pharmaceuticals, Inc. Boston,MA. October 2019.

            21. Ultomiris. Clinicaltrial.gov. Accessed on 01/03/19 . Available at: https://clinicaltrials.gov/ct2/show/NCT03056040

            22. Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Ojeda Gutierrez E, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Röth A, Peffault de Latour R. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2018 Dec 3. pii: blood-2018-09-876805. doi: 10.1182/blood-2018-09-876805.

            23. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2018 Dec 3. pii: blood-2018-09-876136. doi: 10.1182/blood-2018-09-876136.

            24. Dhillon S. Eculizumab: A Review in Generalized Myasthenia Gravis. Drugs. 2018;78(3):367-376. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845078/

            25. Clinicaltrials.gov. A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study). Available at: https://clinicaltrials.gov/ct2/show/NCT01892345

            26. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016 Jan;31(1):15-39.

            27. Clinicaltrials.gov. Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS). NCT02949128. Available at: https://clinicaltrials.gov/ct2/show/NCT02949128

            28. Clinicaltrials.gov. Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS). NCT03131219. Available at: https://clinicaltrials.gov/ct2/show/NCT03131219

            29. Uplizna (inebilizumab-cdon) [package insert]. Viela Bio, Inc. Gaithersburg, MD. June 2020.

            30. Enspryng (satralizumab-mwge) [package insert]. Genentech, Inc. South San Francisco, CA. August 2020.

            Codes:
            (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

            CPT*
            C9052

              HCPCS
              J1300
              J1303
                * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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                Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

                The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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