Effective Date

Date of Origin 

10-01-2024            

10-01-2024

ZILBRYSQ®

(zilucoplan)

Injection for subcutaneous use

Treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive

1

Generalized Myasthenia Gravis (gMG)

Myasthenia gravis (MG) is a neuromuscular disorder primarily characterized by muscle weakness and muscle fatigue. Although the disorder usually becomes apparent during adulthood, symptom onset may occur at any age. The condition may be restricted to certain muscle groups, particularly those of the eyes (ocular myasthenia), or may become more generalized (generalized myasthenia gravis [gMG]), involving multiple muscle groups. Most individuals with myasthenia gravis develop weakness and drooping of the eyelids (ptosis); weakness of eye muscles, resulting in double vision (diplopia); and excessive muscle fatigue following activity. Additional features commonly include weakness of facial muscles; impaired speech (dysarthria); difficulties chewing and swallowing (dysphagia); and weakness of the upper arms and legs (proximal limb weakness). In addition, about 10% of affected patients may develop potentially life-threatening complications due to severe involvement of muscles used during breathing (myasthenic crisis). Myasthenia gravis results from an abnormal immune reaction in which antibodies inappropriately attack and gradually injure certain receptors in muscles that receive nerve impulses (antibody-mediated autoimmune response).(2)

The course of myasthenia gravis is highly variable. For example, the degree of muscle weakness may vary over hours, from day to day, or over weeks and months, tending to increase with repeated muscle use and to improve with rest. In addition, particularly during the first years after disease onset, some affected individuals may experience alternating periods in which symptoms temporarily subside or worsen. A short-term aggravation of symptoms may be triggered by a variety of factors, including infection, excessive physical activity, menstruation, and after delivery of a child.(2)

Corticosteroids are a standard treatment for MG but may cause transient worsening within the first 2 weeks and patients should be monitored closely for this possibility. As a result, a MG consensus panel lists corticosteroids as one of many agents to avoid or use with caution in MG. A nonsteroidal immunosuppressive agent should be used initially in treating MG. Nonsteroidal immunosuppressive agents that can be used in MG include azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus. For nonsteroidal immunosuppressive agents, once treatment goals have been achieved and maintained for 6 months to 2 years, the immunosuppressive dose should be tapered slowly to the minimal effective amount. Patients must be monitored for potential adverse effects and complications from immunosuppressive drugs. Changing to an alternative immunosuppressive agent should be considered if adverse effects and complications are medically significant or create undue hardship for the patient.(3)

Plasma exchange and IVIg are appropriately used as short-term treatments in patients with MG with life-threatening signs such as respiratory insufficiency or dysphagia; in preparation for surgery in patients with significant bulbar dysfunction; when a rapid response to treatment is needed; when other treatments are insufficiently effective; and prior to beginning corticosteroids if deemed necessary to prevent or minimize exacerbations. The use of IVIg as maintenance therapy can be considered for patients with refractory MG or for those in whom immunosuppressive agents are contraindicated. Refractory MG is defined as post-intervention status is unchanged or worse after corticosteroids and at least 2 other immunosuppressive agents, used in adequate doses for an adequate duration, with persistent symptoms or side effects that limit functioning, as defined by the patient and physician.(3)

The time of onset and maximal effect varies between products. Azathioprine, mycophenolate mofetil, cyclosporine, and tacrolimus can take between 6 to 12 months to onset and up to 1 to 2 years to see maximal effect in MG. Rapid therapies such as plasmapheresis or IVIg therapy take approximately 1 week to onset and between 1 to 3 weeks to see maximal effect.(7)

Certain medications have established pharmacologic adverse effects on neuromuscular transmission. Use of these medications in a patient with MG can further reduce the effectiveness of neuromuscular transmission and cause increased clinical weakness. However, reported associations do not necessarily mean these medications should never be prescribed in MG. Clinical judgment and the risk-to-benefit ratio of the drug should be considered when it is deemed important for a patient’s treatment. Medications that can cause a significant increase in weakness in patients with MG include fluoroquinolones, botulinum toxin, ketolides (particularly telithromycin) and aminoglycoside antibiotics, beta blockers, macrolide antibiotics, procainamide, quinidine, quinine, and magnesium. A number of other medications may unmask or exacerbate MG, particularly the neuromuscular blocking agents used during anesthesia, which can lead to prolonged postoperative weakness and ventilator dependence.(3)

Efficacy

The efficacy of ZILBRYSQ for the treatment of gMG in adult patients who are anti-acetylcholine receptor (AChR) positive was established in a 12-week, multicenter, randomized, double-blind placebo-controlled study (NCT04115293). Patients who met the following criteria at screening were enrolled in this study:(1)

• Myasthenia Gravis Foundation of America (MGFA) clinical classification class II to IV
• Positive serology for AChR binding autoantibodies
• AG-Activities of Daily Living (MG-ADL) total score of greater than or equal to 6
• Those on MG therapy prior to screening (including acetylcholinesterase [AChE] inhibitors, steroids, or non-steroidal immunosuppressive therapies either in combination or alone), needed to maintain a stable dose

The primary efficacy endpoint was a comparison of the change from baseline between treatment groups in the MG-ADL total score after 12 weeks of treatment. The efficacy of ZILBRYSQ was also measured using the Quantitative MG (QMG) total score. Other secondary endpoints included the proportion of patients with improvements of at least 3 in the MG-ADL total score and at least 5 points in the QMG total score at week 12 without rescue therapy. At week 12, treatment with ZILBRYSQ demonstrated a statistically significant improvement from baseline compared to placebo for MG-ADL total score and QMG total score.(1)

MG-ADL:(4)

The MGFA clinical classification divides MG into 5 main classes and several subclasses. It is designed to identify subgroups of patients with MG who share distinct clinical features or severity of disease that may indicate different prognoses or responses to therapy:(6)

The QMG is a 13-item scale used to quantify disease severity in myasthenia gravis (MG). The scale measures ocular, bulbar, respiratory, and limb function, grading each finding and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits). Drawbacks to the QMG are that it requires special instrumentation (dynamometer for grip strength and spirometer for vital capacity) and is time consuming, requiring 25-30 minutes to perform. The QMG has also been criticized as not being fully representative of MG disease activity due to the lack of weighting of different domains.(8)

Safety

ZILBRYSQ is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). It contains a boxed warning for an increased risk of meningococcal infections. All patients without a history of meningococcal vaccination should receive the vaccine at least two weeks prior to receiving the first dose of ZILBRYSQ.(1) 

ZILBRYSQ is contraindicated in patients with unresolved Neisseria meningitidis infection.(1)

1

ZILBRYSQ prescribing information. UCB, Inc. May 2024.

2

National Institute of Neurological Disorders and Stroke. Myasthenia Gravis Fact Sheet. NIH Publication No. 17-768. July 2018.

3

Narayanaswami P, Sanders DB, Wolfe G, et al. International Consensus Guidance for Management of Myasthenia Gravis. Neurology. 2021;96(3):114-122. doi:10.1212/wnl.0000000000011124.

4

Wincentsen J. MG Activities of Daily Living (MG-ADL) scale. Conquer Myasthenia Gravis. Published September 29, 2022. https://myastheniagravis.org/mg-activities-of-daily-living-mg-adl-scale/

5

Reference no longer used.

6

Jayam Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune Dis. 2012;2012:874680. doi:10.1155/2012/874680.

7

Alhaidar MK, Abumurad S, Soliven B, Rezania K. Current treatment of myasthenia gravis. Journal of Clinical Medicine. 2022;11(6):1597. doi:10.3390/jcm11061597.

8

Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative Myasthenia gravis score. Journal of Clinical Neuromuscular Disease. 2012;13(4):201-205. doi:10.1097/cnd.0b013e31824619d5.

Zilbrysq

zilucoplan sodium subcutaneous soln pref syr

16.6 MG/0.416ML ; 23 MG/0.574ML ; 32.4 MG/0.81ML

M ; N ; O ; Y

N

Zilbrysq 16.6 mg/0.416 mL

zilucoplan

16.6 MG/0.416ML

28

Syringes

28

DAYS

Zilbrysq 23 mg/0.574 mL

zilucoplan

23 MG/0.574ML

28

Syringes

28

DAYS

Zilbrysq 32.4 mg/0.81 mL

zilucoplan

32.4 MG/0.81ML

28

Syringes

28

DAYS

Zilbrysq

zilucoplan sodium subcutaneous soln pref syr

16.6 MG/0.416ML ; 23 MG/0.574ML ; 32.4 MG/0.81ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zilbrysq 16.6 mg/0.416 mL

zilucoplan

16.6 MG/0.416ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zilbrysq 23 mg/0.574 mL

zilucoplan

23 MG/0.574ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zilbrysq 32.4 mg/0.81 mL

zilucoplan

32.4 MG/0.81ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of generalized Myasthenia Gravis (gMG) AND ALL of the following:
      1. The patient has a positive serological test for anti-AChR antibodies (medical records required) AND 
      2. The patient has a Myasthenia Gravis Foundation of America (MGFA) clinical classification class of II-IVb AND
      3. The patient has a MG-Activities of Daily Living total score of greater than or equal to 6 AND
      4. ONE of the following:
         1. The patient’s current medications have been assessed and any medications known to exacerbate myasthenia gravis (e.g., beta blockers, procainamide, quinidine, magnesium, anti-programmed death receptor-1 monoclonal antibodies, hydroxychloroquine, aminoglycosides) have been discontinued OR
         2. Discontinuation of the offending agent is NOT clinically appropriate AND
      5. ONE of the following:
         1. The patient has tried and had an inadequate response to at least ONE conventional agent used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) OR
         2. The patient has an intolerance or hypersensitivity to ONE conventional agent used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) OR
         3. The patient has an FDA labeled contraindication to ALL conventional agents used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) OR
         4. The patient required chronic intravenous immunoglobulin (IVIG) OR
         5. The patient required chronic plasmapheresis/plasma exchange OR
      6. If the client has preferred agent(s), then ONE of the following:
         1. The patient has tried and had an inadequate response to Ultomiris (ravulizumab-cwvz), Rystiggo (rozanolixizumab-noli), Vyvgart (efgartigimod), or Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) OR
         2. The patient has an intolerance or hypersensitivity to Ultomiris (ravulizumab-cwvz), Rystiggo (rozanolixizumab-noli), Vyvgart (efgartigimod), or Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) OR
         3. The patient has an FDA labeled contraindication to ALL of the following: 
            1. Ultomiris (ravulizumab-cwvz) AND
            2. Rystiggo (rozanolixizumab-noli) AND
            3. Vyvgart (efgartigimod) AND
            4. Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) OR
   2. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA approved indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with Rystiggo (rozanolixizumab-noli), Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), Vyvgart (efgartigimod), or Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for the requested indication AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval:  3 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with Rystiggo (rozanolixizumab-noli), Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), Vyvgart (efgartigimod), or Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for the requested indication AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Universal QL

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication​​​​​​​

Length of Approval: up to 12 months