RAVULIZUMAB-CWVZ INJ,SOLN
Clinical Criteria Summary
Document 428
Exclusion Criteria
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Thymectomy within 12 months
- Concomitant therapy with rituximab, neonatal Fc receptor antagonists (e.g., efgartigimod), or any other complement inhibitor (e.g., eculizumab)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable while on ravulizumab-cwvz)
Inclusion Criteria (All must be met)
- Care provided by a VA/VA Community Care neurology provider or locally designated expert
- Diagnosis of acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG)
- Patient is not a candidate for or has opted against thymectomy
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 6
- Vaccination against pneumococcal disease and Neisseria meningitidis with both Meningococcal conjugate vaccine (MenACWY) and Meningococcal serogroup B vaccine
Additional Inclusion Criteria (One of the following must be met)
- Inadequate symptom control to maximally tolerated pyridostigmine AND at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- Lack of symptom control despite 4 or more courses of plasma exchange, high-dose steroid bursts and/or intravenous immune globulin in a 12-month or less period
Vaccination & Prophylaxis Notes
- In emergent cases where waiting to initiate ravulizumab-cwvz at least two weeks after completion of vaccination is not possible, patients should begin the vaccination series at the time of initial dosing and be provided with appropriate prophylaxis
Document 429
Indication & Patient Population
- • Treatment of Neuromyelitis optica spectrum disorder (NMOSD)
- • Restricted to patients who are anti-aquaporin-4 (AQP4) antibody-positive
Dosing & Administration
- • Dosage form: Injection (300 mg/mL in a single dose vial)
- • Route and frequency: Intravenous infusion every 8 weeks
- • Dosing is weight-based:
- Loading dose: 2,400 mg (40 kg to <60 kg), 2,700 mg (60 kg to <100 kg), 3,000 mg (≥100 kg)
- Maintenance dose: 3,000 mg (40 kg to <60 kg), 3,300 mg (60 kg to <100 kg), 3,600 mg (≥100 kg), starting 2 weeks after loading dose
REMS & Safety Requirements
- • Prescribers must enroll in the Ultomiris REMS program
- • Patients must be counseled regarding the risk of meningococcal infections/sepsis
- • Patients must be provided with REMS educational materials
- • Patients must be vaccinated with meningococcal vaccines prior to starting therapy
Clinical Considerations
- • Appropriate as a biologic therapy option for NMOSD
- • Disease severity, risks, and patient-specific considerations should be taken into account when choosing which therapy to start
Document 693
Exclusion Criteria
- Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae active infection
- Active, clinically significant infection
- Concomitant biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable)
Inclusion Criteria
- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Contraindication, intolerance, or lack of therapeutic response to rituximab
Document 694
Exclusion Criteria
- Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS)
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Concomitant therapy with rituximab or any other complement inhibitor such as eculizumab
- Concomitant chronic therapy with plasma exchange
- Inclusion Criteria (All must be met)
- Prescribed by or in consultation with a VA or VA Community Care nephrology or hematology provider or locally designated expert
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Additional Inclusion Criteria (One of the following must be met)
- Patient requires treatment of aHUS with documentation ruling out Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS) and thrombotic thrombocytopenia purpura (TTP) (e.g., clinical evaluation and/or rule out of ADAMTS13 deficiency)
- Patient requires prophylaxis in renal transplant to ensure aHUS does not recur in the transplanted kidney
Document 695
Exclusion Criteria
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria
- Must be prescribed by or in consultation with a VA or VA Community Care hematology, oncology, immunology provider or locally designated expert
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Laboratory-confirmed diagnosis of PNH, as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells [RBC]) via Flow Cytometry
- Documentation of Flow Cytometry pathology report must indicate presence of PNH-type RBC
- Must have a lactate dehydrogenase (LDH) level of 1.5 times the upper limit of the normal range (unless switching from eculizumab; laboratory results with reference range must be available for review)
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Indication & Patient Population
- • Generalized Myasthenia Gravis (gMG) in patients who are anti-acetylcholine receptor antibody-positive (AChR+)
- • Not supported for use in other antibody types including MuSK+, LRP4+, or seronegative disease
Dosing & Administration
- • Only the IV formulation is currently approved for myasthenia gravis
- • Dosing is weight-based with a loading dose followed by maintenance doses every 8 weeks starting 2 weeks after the loading dose
- • Weight-based dosing:
- 40 kg to less than 60 kg: Loading 2,400 mg; Maintenance 3,000 mg
- 60 kg to less than 100 kg: Loading 2,700 mg; Maintenance 3,300 mg
- 100 kg or more: Loading 3,000 mg; Maintenance 3,600 mg
Safety & REMS Requirements
- • Prescribers must enroll in the Ultomiris REMS program
- • Must counsel patients about the risk of meningococcal infections/sepsis and provide REMS educational materials
- • Patients must be vaccinated with meningococcal vaccines prior to therapy
- • Monitor for infusion-related reactions, severe meningococcal infection, other infections, diarrhea, and headache
Place in Therapy & Treatment Context
- • Steroid-sparing treatment option for AChR+ gMG
- • Considered as add-on therapy when traditional oral immunosuppressants (azathioprine, mycophenolate, steroids) with or without acetylcholinesterase inhibitor (pyridostigmine) are ineffective
- • Offers a less frequent infusion schedule compared to eculizumab
- • Not studied in combination with plasma exchange, intravenous immunoglobulin (IVIg), rituximab, efgartigimod, or other complement inhibitors