Medicare Advantage

Medical Policy

Title:

Efgartigimod alfa - fcab (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo)

Policy #:

MA08.142c

Policy

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

EFGARTIGIMOD ALFA-FCAB (VYVGART) AND EFGARTIGIMOD ALFA AND HYALURONIDASE-QVFC (VYVGART HYTRULO)

Efgartigimod alfa-fcab (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) is are considered medically necessary and, therefore, covered for the treatment of adult individuals with generalized myasthenia gravis (gMG) when all of the following criteria are met:

The individual is anti-acetylcholine receptor (AChR) antibody-positive.
The Individual meets Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IV.
The individual has a Myasthenia Gravis--Specific Activities of Daily Living scale (MG-ADL) total score of five or greater.
The individual is on a stable dose of MG therapy either in combination or alone of any of the following medication:

acetylcholinesterase (AChE) inhibitors
steroids
non-steroidal immunosuppressive therapies (NSISTs)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for efgartigimod alfa-fcab (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo), are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

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

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

When coverage of efgartigimod alfa-fcab (Vyvgart) or efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

Guidelines

DRUG INFORMATION

In accordance with US Food and Drug Administration (FDA) prescribing information, efgartigimod alfa-fcab (Vyvgart) is administered as an intravenous infusion is 10 mg/kg over one hour once weekly for 4 weeks. In individuals weighing 120 kg or more, the recommended dose of VYVGART is 1200 mg per infusion. Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) is administered subcutaneously as dose is 1,008 mg / 11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, efgartigimod alfa-fcab (Vyvgart) and Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

MYASTHENIA GRAVIS FOUNDATION OF AMERICA (MGFA) CLINICAL CLASSIFICATION

Class I: Any ocular muscle weakness; may have weakness of eye closure. All other muscle strength is normal.
Class II: Mild weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

A. IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

A. IIIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IIIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

A. IVa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IVb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

Class V: Defined as intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of a feeding tube without intubation places the individual in class IVb.

MG Activities of Daily Living (MG-ADL) Profile

Grade	Score
Activities of Daily Living (ADL)	0	1	2	3
Talking	normal	Intermittent slurring or nasal speech.	Constant slurring or nasal, but can be understood	Difficult to understand speech
Chewing	normal	Fatigue with solid food	Fatigue with soft food	Gastric tube
Swallowing	normal	Rare episode of choking	Frequent choking necessitating changes in diet	Gastric tube
Breathing	normal	Shortness of breath with exertion	Shortness of breath at rest	Ventilator dependence
Impairment of ability to brush teeth or comb hair	none	Extra effort, but no rest periods needed.	Rest periods needed	Cannot do one of these functions
Impairment of ability to arise from a chair	none	Mild, sometimes uses arms	Moderate, always uses arms	Severe, requires assistance
Double vision	none	Occurs, but not daily	Daily, but not constant	Constant
Eyelid droop	none	Occurs, but not daily	Daily, but not constant	Constant

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Efgartigimod alfa-fcab (Vyvgart) was approved by the FDA on December 17, 2021 for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-acetylcholine receptor (AChR) antibody positive.

Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) was approved by the FDA on June 20,2023 for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-acetylcholine receptor (AChR) antibody positive.

PEDIATRIC USE

The safety and effectiveness of efgartigimod alfa-fcab (Vyvgart) or efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) for generalized myasthenia gravis (gMG) have not been established in the pediatric population.

Description

GENERALIZED MYASTHENIA GRAVIS

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles. The muscle weakness usually worsens after periods of activity and improves after periods of rest. Muscles that control movements of the eye and eyelid, facial expression, chewing, talking, and swallowing are often involved, but those that control breathing and neck and limb movements may also be involved. This weakness is a result of an antibody-mediated, T-cell dependent, immunological attack directed at proteins in the postsynaptic membrane of the neuromuscular junction. MG has an annual incidence of about 7 to 23 cases per million. It most often begins before the age of 40 in women and after age 60 in men.

PEER-REVIEWED LITERATURE

SUMMARY

The safety, efficacy, and tolerability of VYVGART was demonstrated in the multicentre, randomized, placebo-controlled Phase 3 ADAPT trial. The ADAPT trial demonstrated that significantly more anti-AChR antibody-positive gMG individuals responded, based on the MG-ADL scale, following treatment with VYVGART compared with placebo (68% vs. 30%; p<0.0001). Responders were defined as having at least a two-point reduction on the MG-ADL scale sustained for four or more consecutive weeks during the first treatment cycle. Additionally, there were significantly more responders on the Quantitative Myasthenia Gravis (QMG) scale following treatment with VYVGART compared with placebo (63% vs. 14%; p<0.0001). Responders were defined as having at least a three-point reduction on the QMG scale sustained for four or more consecutive weeks during the first treatment cycle. The most common adverse events in ADAPT trial were respiratory tract infection (33% vs 29% placebo), headache (32% vs 29% placebo), and urinary tract infection (10% vs. 5% placebo).

ADAPT trial established the effectiveness of efgartigimod alfa-fcab intravenous (IV) formulation for the treatment of AChR antibody positive generalized myasthenia gravis (gMG) in adult individuals. In trial (ADAPTsc), VYVGART HYTRULO demonstrated a comparable pharmacodynamic effect on AChR antibody reduction to the efgartigimod alfa-fcab IV formulation, which established the efficacy of VYVGART HYTRULO. This study enrolled110 individuals who were randomized and received one cycle of once weekly administrations for 4 weeks, of either VYVGART HYTRULO subcutaneously (n=55) or efgartigimod alfa-fcab intravenously (n=55).

The maximum mean reduction in AChR-Ab level was observed at week 4, with a mean reduction of 62.2% and 59.7% in the VYVGART HYTRULO SC and efgartigimod alfa-fcab IV arm, respectively. The decrease in total IgG levels followed a similar pattern.

Most common adverse events were injection site reactions occurred in 38% of individuals receiving VYVGART HYTRULO.

The primary endpoint was met, with a comparable mean reduction in total IgG with the subcutaneous versus the IV formulation. Secondary endpoints were met in 69.1% of individuals who responded on the MG-ADL score and 65.5% of individuals who responded on the QMG-score. From this study, individuals could enter an open label to receive VYVGART HYTRULO to evaluate the long-term safety and tolerability of subcutaneous formulation.

OFF-LABEL INDICATIONS

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

References

American Hospital Formulary Service (AHFS). Drug Information. Efgartigimod alfa - fcab (Vyvgart). [Lexicomp Web site] 04/21/22. Available at: https://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/6684461 [via subscription only]. Accessed August 22, 2023.

Argenx BV., Zwijnaarde, Belgium. Efgartigimod alfa - fcab (Vyvgart) labeling.12/2021. Available at: https://argenx.com/product/vyvgart-prescribing-information.pdf. Accessed August 22, 2023.

American Academy of Neurology(AAN). Myasthenia gravis activities of daily living profile. [ANN Web site]. 04/01/1999.

ClinicalTrials.gov. An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness (ADAPT). ClinicalTrials.gov Identifier: NCT03669588. First Posted: September 13, 2018; Last Update Posted: March 18, 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03669588. Accessed August 22, 2023.

ClinicalTrials.gov. Evaluating the Pharmacodynamic Noninferiority of Efgartigimod PH20 SC Administered Subcutaneously as Compared to Efgartigimod Administered Intravenously in Patients With Generalized Myasthenia Gravis (ADAPTsc). ClinicalTrials.gov Identifier: NCT04735432. First Posted: February 3, 2021; Last Update Posted: February 28, 2023. Available at: https://clinicaltrials.gov/study/NCT04735432?cond=Generalized Myasthenia Gravis&term=efgartigimod &rank=2&tab=table.

Accessed August 22, 2023.

Elsevier’s Clinical Pharmacology Compendium .Efgartigimod alfa - fcab (Vyvgart).[Clinical Key Web site]. 12/21/21. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed August 22, 2023.

Elsevier’s Clinical Pharmacology Compendium .Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo).[Clinical Key Web site]. 06/29/23. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed August 22, 2023.

Lexi-Drugs Compendium. Efgartigimod alfa - fcab (Vyvgart). [Lexicomp Online Web site]. 08/04/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 22, 2023.

Lexi-Drugs Compendium. Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) . [Lexicomp Online Web site]. 06/22/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 22, 2023.

Jaretzki A 3rd, Barohn RJ, Ernstoff RM. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000;55(1):16-23.

Sathasivam S. Diagnosis and management of myasthenia gravis. Prog Neurol Psychiatry. 2014;18(1):6-14.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Efgartigimod alfa - fcab. [Micromedex Web site]. 08/11/23. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 22, 2023.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo). [Micromedex Web site]. 08/11/23. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Efgartigimod alfa - fcab (Vyvgart). Package insert. [FDA Web site]. 12/17/2021. Available at:https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo). Package insert. [FDA Web site]. 06/20/2023. Available at:https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Efgartigimod alfa - fcab (Vyvgart). [FDA Web site]. Original: 12/17/21. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo). [FDA Web site]. Original: 06/20/23. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Efgartigimod alfa - fcab (Vyvgart) prescribing information & approval letter. [FDA Web site]. 12/2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761195s000lbl.pdf. Accessed August 22, 2023.

US Food and Drug Administration (FDA). Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) prescribing information & approval letter. [FDA Web site]. 06/2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761195s000lbl.pdf. Accessed August 22, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

G70.00 Myasthenia gravis without (acute) exacerbation

G70.01 Myasthenia gravis with (acute) exacerbation

HCPCS Level II Code Number(s)

THE FOLLOWING CODES ARE USED TO REPRESENT EFGARTIGIMOD ALFA-FCAB (VYVGART ™):

J9332 Injection, efgartigimod alfa-fcab, 2mg

THE FOLLOWING CODES ARE USED TO REPRESENT HYALURONIDASE-QVFC (VYVGART HYTRULO®):

J9334 Injection, efgartigimod alfa, 2 mg and hyaluronidase-qvfc

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.142c:

01/02/2024

This policy has been identified for the HCPCS code update, effective 01/02/2024.

The following HCPCS codes termed from this policy:

C9399 Unclassified drugs or biologics
J3590 Unclassified biologics

The following HCPCS code has been added to this policy:

J9334 Injection, efgartigimod alfa, 2 mg and hyaluronidase-qvfc

Revisions From MA08.142b:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
10/09/2023	This version of the policy will become effective 10/09/2023. This policy has been updated to communicate the Company’s coverage position and criteria for hyaluronidase-qvfc (Vyvgart Hytrulo). The following HCPCS codes have been added to this policy: THE FOLLOWING CODES ARE USED TO REPRESENT HYALURONIDASE-QVFC (VYVGART HYTRULO®): C9399 Unclassified drugs or biologics J3590 Unclassified biologics

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

10/09/2023

This version of the policy will become effective 10/09/2023.

This policy has been updated to communicate the Company’s coverage position and criteria for hyaluronidase-qvfc (Vyvgart Hytrulo).

The following HCPCS codes have been added to this policy:

THE FOLLOWING CODES ARE USED TO REPRESENT HYALURONIDASE-QVFC (VYVGART HYTRULO®):

C9399 Unclassified drugs or biologics

J3590 Unclassified biologics

Revisions From MA08.142a:

04/19/2023	This policy has been reissued in accordance with the Company's annual review process.
07/01/2022	This policy has been identified for the HCPCS code update, effective 07/01/2022. The following HCPCS codes termed from this policy: C9399 Unclassified drugs or biologics J3590 Unclassified biologics The following HCPCS codes have been added to this policy: J9332 Injection, efgartigimod alfa-fcab, 2mg

Revisions From MA08.142:

3/14/2022

This version of the policy will become effective 3/14/2022.

This new policy has been issued to communicate the Company’s coverage position and criteria for efgartigimod-alfa (Vyvgart).

Version Effective Date:

1/1/2024

Version Issued Date:

1/2/2024

Version Reissued Date: