Coverage Policy Manual
Policy #: 2023019
Category: Pharmacy
Initiated: May 2023
Last Review: May 2024
  Mirvetuximab soravtansine-gynx (e.g. Elahere)
Description:
Mirvetuximab soravtansine-gynx (e.g., Elahere) is a first-in-class antibody-drug conjugate indicated for the treatment of adult individuals with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Individuals are selected for therapy based on an FDA-approved test.
 
The antibody is a chimeric immunoglobulin G1 (IgG1) directed against folate receptor alpha (FRα). The small molecule, DM4, is a microtubule inhibitor attached to the antibody via a cleavable linker. Upon binding to FRα, mirvetuximab soravtansine-gynx is internalized followed by intracellular release of DM4 via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, resulting in cell cycle arrest and apoptotic cell death.
 
Mirvetuximab soravtansine-gynx (e.g., Elahere) carries a black box warning for ocular toxicity. Potential severe ocular toxicities include visual impairment keratopathy, dry eye, photophobia, eye pain, and uveitis.
 
Treatment of ovarian cancer typically consists of surgery and platinum-based combination chemotherapy. Platinum-resistant ovarian cancer (PROC) is common. Most individuals with recurrent PROC will move on to single-agent chemotherapy, which has limited benefit in this setting and low response rates.
 
Regulatory Status
 
Mirvetuximab soravtansine-gynx (e.g., Elahere) was approved by the U.S. Food and Drug Administration (FDA) on November 14, 2022, for the treatment of adult individuals with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Individuals are selected for therapy based on an FDA-approved test.
 
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Prior Approval is required for mirvetuximab soravtansine-gynx (e.g., Elahere).
 
The initial use of this drug requires documentation of direct physician involvement (MD/DO) in the ordering and evaluation, as well as signature, in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.
 
For members of plans that utilize an oncology benefits management program, Prior Approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.
 
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective May 15, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Mirvetuximab soravtansine-gynx meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
FDA Approved Indications
 
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 18 years of age or older (Elahere, 2022); AND
    2. Individual is female (Matulonis, 2023); AND
    3. Individual has a diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer (NCCN 2A); AND
    4. Individual must have received at least one but no more than three prior systemic lines of anticancer therapy (NCCN 2A); AND
    5. Individual has FRα-positive expression as defined by an FDA approved test (NCCN 2A); AND
    6. Individual must have an ECOG performance status of 0 to 1* (Matulonis, 2023); AND
    7. Individual is using mirvetuximab soravtansine-gynx as a single agent (Matulonis, 2023); AND
    8. Must be dosed in accordance with the FDA label.  
 
CONTINUED APPROVAL for up to 1 year:  
 
    1. Individual has not experienced disease progression during mirvetuximab soravtansine-gynx treatment (Elahere, 2022); AND
    2. Individual has not experienced any unacceptable toxicities from the drug (Elahere, 2022); AND
    3. Individual will be using mirvetuximab soravtansine-gynx as a single agent (Matulonis, 2023); AND
    4. Individual has an ECOG performance status of 0-1* (Matulonis, 2023); AND
    5. Must be dosed in accordance with the FDA label.  
 
Off Label Indications
 
For off-label indications, authorizations will not exceed 6 mg/kg adjusted body weight unless medical literature supports a higher dose.
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual has a diagnosis of epithelial ovarian cancer/fallopian tube cancer/peritoneal cancer/carcinosarcoma (Malignant Mixed Mullerian Tumors)/clear cell carcinoma or mucinous carcinoma of the ovary/Grade 1 Endometrioid carcinoma; AND
2. Individual will receive mirvetuximab soravtansine-gynx as a single agent or in combination with bevacizumab for platinum-resistant disease persistence or recurrence in folate receptor-alpha expressing tumors (NCCN 2A):
a. For progression on primary, maintenance, or recurrence therapy; OR
b. For stable or persistent disease (if not on maintenance therapy): OR
c. For complete remission and relapse less than 6 months after completing chemotherapy (immediate relapse is not covered); OR
3. Individual has a diagnosis of low-grade serous carcinoma with either serous or borderline epithelial histology and will receive mirvetuximab soravtansine-gynx as a single agent or in combination with bevacizumab for platinum-resistant disease persistence or recurrence in folate receptor-alpha expressing tumors (platinum-sensitive disease is not covered) (NCCN 2A).
 
CONTINUED APPROVAL for up to 1 year:
 
1. Individual has not experienced disease progression during mirvetuximab soravtansine-gynx treatment; AND
2. Individual has not experienced any unacceptable toxicities from the drug; AND
3. Individual will be using mirvetuximab soravtansine-gynx as a single agent or in combination with bevacizumab.
 
*The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).  
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of mirvetuximab soravtansine-gynx is 6 mg/kg adjusted body weight administered once every 3 weeks until disease progression or unacceptable toxicity.
 
Mirvetuximab soravtansine-gynx is available as a 100mg/20mL solution for injection.
 
Mirvetuximab soravtansine-gynx should be administered as an intravenous infusion by a healthcare professional.
 
Adjusted body weight can be calculated here: https://www.mdcalc.com/calc/68/ideal-body-weight-adjusted-body-weight
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Mirvetuximab soravtansine-gynx, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, mirvetuximab soravtansine-gynx, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Date May 17, 2023 to May 14, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Mirvetuximab soravtansine-gynx meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
    1. Individual is 18 years of age or older (Elahere, 2022); AND
    2. Individual is female (Matulonis, 2023); AND
    3. Individual has a diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer (NCCN 2A); AND
    4. Individual must have received at least one but no more than three prior systemic lines of anticancer therapy (NCCN 2A); AND
    5. Individual has FRα-positive expression as defined by an FDA approved test (NCCN 2A); AND
    6. Individual must have an ECOG performance status of 0 to 1* (Matulonis, 2023); AND
    7. Individual is using mirvetuximab soravtansine-gynx as a single agent (Matulonis, 2023); AND
    8. Must be dosed in accordance with the FDA label.  
 
CONTINUED APPROVAL for up to 1 year:  
    1. Individual has not experienced disease progression during mirvetuximab soravtansine-gynx treatment (Elahere, 2022); AND
    2. Individual has not experienced any unacceptable toxicities from the drug (Elahere, 2022); AND
    3. Individual will be using mirvetuximab soravtansine-gynx as a single agent (Matulonis, 2023); AND
    4. Individual has an ECOG performance status of 0-1* (Matulonis, 2023); AND
    5. Must be dosed in accordance with the FDA label.  
 
*The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).  
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of mirvetuximab soravtansine-gynx is 6 mg/kg adjusted body weight administered once every 3 weeks until disease progression or unacceptable toxicity.
 
Mirvetuximab soravtansine-gynx is available as a 100mg/20mL solution for injection.
 
Mirvetuximab soravtansine-gynx should be administered as an intravenous infusion by a healthcare professional.
 
Adjusted body weight can be calculated here: https://www.mdcalc.com/calc/68/ideal-body-weight-adjusted-body-weight
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Mirvetuximab soravtansine-gynx, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, mirvetuximab soravtansine-gynx, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
In the phase III FORWARD I trial, mirvetuximab soravtansine-gynx was studied in platinum-resistant epithelial ovarian cancer. No significant improvement in progression-free survival (PFS) was found for Elahere compared to chemotherapy. However, upon review of secondary endpoints, such as overall response rate (ORR), Elahere was favored in the subset of patients with high FRα expression, leading to its evaluation in PROC tumors, as in Study 0417.
 
In Study 0417 (NCT04296890), the efficacy of mirvetuximab soravtansine-gynx was evaluated in a single-arm trial of patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (n=106). Patients were permitted to receive up to three prior lines of systemic therapy. All patients were required to have received prior bevacizumab. The trial enrolled patients whose tumors were positive for FRα expression as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. Patients received mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. Tumor response assessments occurred every 6 weeks for the first 36 weeks and every 12 weeks thereafter. The major efficacy outcome measures were investigator-assessed ORR and duration of response (DOR) evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. In the efficacy-evaluable population of patients who had platinum-resistant, measurable disease and received at least one dose (104 patients), the confirmed ORR was 31.7% and the median DOR was 6.9 months.
 
2024 Update
A phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer was conducted. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes.
 
A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%).
 
Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Moore KN, Angelergues A, Konecny GE, 2023)
 
CPT/HCPCS:
C9146Injection, mirvetuximab soravtansine-gynx, 1 mg
C9399Unclassified drugs or biologicals
J3490Unclassified drugs
J3590Unclassified biologics
J9063Injection, mirvetuximab soravtansine-gynx, 1 mg
J9999Not otherwise classified, antineoplastic drugs
References: Elahere [package insert]. Waltham, MA: ImmunoGen, Inc; 2022.

Matulonis, U.A., et al.(2023) Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. doi: 10.1200/JCO.22.01900. Epub 2023 Jan 30. PMID: 36716407; PMCID: PMC10150846.

Moore, K.N, et al.(2021) Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. doi: 10.1016/j.annonc.2021.02.017. Epub 2021 Mar 2. PMID: 33667670.

National Comprehensive Cancer Network (NCCN).(2023) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. NCCN Clinical Practice Guidelines in Oncology, Version 1.2023. Plymouth Meeting, PA: NCCN; 2022.

Pai, M.(2023) Ideal Body Weight and Adjusted Body Weight. MD+CALC. https://www.mdcalc.com/calc/68/ideal-body-weight-adjusted-body-weight.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.