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| Mirvetuximab soravtansine-gynx (e.g. Elahere) | |
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| 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.
Mirvetuximab soravtansine-gynx (e.g., Elahere) received full approval from the U.S. Food and Drug Administration for the treatment of folate receptor alpha-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal adult cancer individuals treated with up to three prior therapies on March 22, 2024. Mirvetuximab soravtansine-gynx (e.g., Elahere) was previously approved under accelerated approval on November 14, 2022.
Coding
See CPT/HCPCS Code section below.
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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.
Approval timeframes may differ for members/participants of Self-Insured plans.
Effective May 7, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Mirvetuximab soravtansine-gynx (e.g., Elahere) 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:
For FDA labeled indications, Mirvetuximab soravtansine-gynx (e.g., Elahere) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.
FDA Labeled Indications:
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)].
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
Off Label Indications:
The use of this drug for off-label indications not listed below is subject to policy 2000030.
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
Policy Guidelines
*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
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications. To view the most recent and complete version of the guideline or Compendium, go online to NCCN.org. Please note, NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Dosage and Administration
Dosing per FDA Guidelines unless otherwise specified below.
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 May 15, 2024 to May 6, 2025
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:
CONTINUED APPROVAL for up to 1 year:
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:
CONTINUED APPROVAL for up to 1 year:
*The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
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:
CONTINUED APPROVAL for up to 1 year:
*The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
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.
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| 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)
2025 Update
Confirmatory MIRASOL phase 3 trial: MIRASOL is a randomized Phase 3 trial of Elahere versus investigator's choice (IC) of single-agent chemotherapy (weekly paclitaxel, pegylated
liposomal doxorubicin, or topotecan). Eligibility criteria include patients with PROC whose tumors express high levels of FRα, using the Ventana FOLR1 Assay, and who have been treated with up to three prior regimens. The primary endpoint of this trial is progression-free survival (PFS) by investigator assessment. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). The trial enrolled 453 patients. Patients were stratified by number of prior lines of therapy (14% had one prior line of therapy, 39% had two prior lines of therapy, and 47% had three prior lines of therapy) and by IC chemotherapy, with paclitaxel as the most commonly chosen (41%), followed by PLD (36%) and topotecan (23%). 62% of patients received prior bevacizumab; 55% received a prior PARP inhibitor. Overall Survival hazard ratio (HR) was 0.67 (95% confidence interval [CI]: 0.50, 0.88; p=0.0046), representing a 33% reduction in risk of death in the Elahere arm compared to the IC chemotherapy arm. Progression Free Survival HR was 0.65 (95% CI: 0.52, 0.81; p<0.0001), representing a 35% reduction in the risk of tumor or cancer progression in the Elahere arm compared to IC chemotherapy. Elahere showed overall fewer Grade 3+ adverse events and a lower rate of discontinuations due to adverse events when compared to the IC chemotherapy control group. The most common (≥20%) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils (Bello, 2024).
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| CPT/HCPCS: | |
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| References: |
Bello, Diana, Toon Van Gorp, Gottfried E. Konecny, et.al.,(2024) Phase 3 MIRASOL (GOG 3045/ENGOT-ov55) trial: Mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in older patients with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRa) expression. (2024): 5580-5580. Elahere [package insert]. Waltham, MA: ImmunoGen, Inc; 2022. Elahere [package insert]. Waltham, MA: ImmunoGen, Inc; 2024. Elahere(2022) package insert ImmunoGen, Inc., Waltham, MA. Revised 03/2024 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. Mirvetuximab Soravtansine in FRa-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. doi: 10.1056/NEJMoa2309169. PMID: 38055253. 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. NCCN Drugs & Biologics Compendium for Mirvetuximab soravtansine-gynx (e.g., Elahere), National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed [April 30, 2025]. To view the most recent and complete version of the Compendium, go online to NCCN.org. NCCN(2024) Clinical Practice Guidelines in Oncology 2024 National Comprehensive Cancer Network, Inc.(2024) Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer v.1.2024. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on May 9, 2024. Pai, M.(2023) Ideal Body Weight and Adjusted Body Weight. MD+CALC. https://www.mdcalc.com/calc/68/ideal-body-weight-adjusted-body-weight. |
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
| CPT Codes Copyright © 2025 American Medical Association. | |