ABBV AbbVie Inc

• ELAHERE is the first and only novel therapy approved in the European Union specifically for patients with folate receptor-alpha (FRα) positive, platinum-resistant ovarian cancer
• ELAHERE represents the first treatment to demonstrate an overall survival benefit in a Phase 3 trial in platinum-resistant ovarian cancer compared with chemotherapy
• VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, the companion diagnostic to identify ovarian cancer patients eligible for ELAHERE, also receives CE Mark

NORTH CHICAGO, Ill., Nov. 18, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the European Commission (EC) granted marketing authorization for ELAHERE^® (mirvetuximab soravtansine) for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who have received one to three prior systemic treatment regimens. ELAHERE is the first and only folate receptor alpha (FRɑ)-directed antibody drug conjugate (ADC) medicine approved in the European Union (EU), as well as Iceland, Liechtenstein, Norway, and Northern Ireland.

"It's been 10 years since a new treatment for platinum-resistant ovarian cancer was approved in the EU, and now oncologists have an effective, new, targeted treatment option for these patients," said Toon Van Gorp, Professor of Gynaecological Oncology at the University of Leuven.

Ovarian cancer is one of the leading causes of death from gynecological cancers worldwide.ⁱ Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, most patients eventually develop platinum-resistant disease.ⁱⁱ Historically, treatment options for patients with platinum-resistant ovarian cancer (PROC) have been limited, and those available often result in adverse events which can negatively impact quality of life.ⁱⁱⁱ

"Ovarian cancer can be devastating, taking women away from precious moments with their family, disrupting careers and the many other important contributions that women make to society," said Clara Mackay, CEO, World Ovarian Cancer Coalition. "In Europe, ovarian cancer is three times more deadly than breast cancer, and having new innovative options allows us to work toward a world where everyone living with ovarian cancer has the best chance of survival and the best quality of life possible, no matter where they live."

In approximately one third of people living with ovarian cancer, the folate-receptor alpha (FRα) biomarker is highly expressed^iv (≥75% of tumor cells with ≥2+ membrane staining intensity). To determine biomarker status, patients can be tested with Roche's VENTANA^® FOLR1 (FOLR1-2.1) RxDx Assay at diagnosis or at the first sign of resistance to platinum-based chemotherapy. AbbVie collaborated with Roche Diagnostics on the newly approved immunohistochemistry (IHC) companion diagnostic test to identify patients who may be eligible for ELAHERE. 

"The approval of ELAHERE by the European Commission provides a much needed clinically meaningful option for patients who receive the heartbreaking news their ovarian cancer has returned, fearing what's next in their treatment journey after they've developed platinum-resistance," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie.

The marketing authorization of ELAHERE is supported by data from MIRASOL: a global, Phase 3 open-label, randomized, controlled trial.

• Trial participants were 18 years of age or older with disease that had progressed while on or after one to three lines of previous therapy. Patient tumors had to express high levels of FRɑ (≥75% of tumor cells with ≥2+ membrane intensity), assessed using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. The primary endpoint was investigator-assessed progression-free survival (PFS). Key secondary endpoints included objective response rate (ORR) and overall survival (OS).
• Results presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated a 35% reduction in the risk of tumor progression or death in patients treated in the ELAHERE arm compared with the investigator's choice (IC) chemotherapy arm, which represented an improvement in PFS [HR 0.65 (95% CI: 0.52, 0.81; p<0.0001)].
• ELAHERE also demonstrated improvement in OS compared with IC chemotherapy, representing a 33% reduction in the risk of death in the ELAHERE arm in comparison to the IC chemotherapy arm [HR 0.67 (95% CI: 0.50, 0.89; p=0.0046)].
• The most common adverse reactions with ELAHERE were blurred vision, nausea, diarrhea, fatigue, abdominal pain, keratopathy, dry eye, constipation, vomiting, decreased appetite, peripheral neuropathy, headache, asthenia, increased aspartate aminotransferase and arthralgia. The most commonly reported serious adverse reaction was pneumonitis.
• Data from the Phase 3 MIRASOL Trial were also published in the New England Journal of Medicine (NEJM).

About the Phase 3 MIRASOL Trial
MIRASOL is a global Phase 3 open-label, randomized, controlled trial that enrolled 453 patients to compare the efficacy and safety of mirvetuximab soravtansine with the investigator's choice of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan) in the treatment of platinum-resistant, high-grade serous ovarian cancer whose tumors express high levels of FRα (≥75% of cells with ≥2+ staining intensity), confirmed with a validated test. Participants had previously received one to three lines of prior therapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Key secondary endpoints included objective response rate (ORR) and overall survival (OS).

More information can be found on www.clinicaltrials.gov (NCT 04209855).

About ELAHERE (mirvetuximab soravtansine)
ELAHERE is a first-in-class ADC composed of a folate receptor alpha binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.

Mirvetuximab soravtansine (approved under the brand name ELAHERE^®) was granted approval by the European Commission in November 2024, and was granted full FDA approval in the United States in March 2024.

Marketing authorization submissions for mirvetuximab soravtansine are under review in multiple other countries.

EU Indication and Important Safety Information about Elahere^® ▼ (mirvetuximab soravtansine)

Indication
ELAHERE (mirvetuximab soravtansine) as monotherapy is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens.

Important Safety Information

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

Special warning and precautions for use
Ocular disorders
Elahere can cause severe ocular adverse reactions, including visual impairment (predominantly blurred vision), keratopathy (corneal disorders), dry eye, photophobia, and eye pain. Patients should be referred to an eye care professional for an ophthalmic exam before initiation of Elahere. Before the start of each cycle, the patient should be advised to report any new or worsening ocular symptoms to the treating physician or qualified individual. If ocular symptoms develop, an ophthalmic exam should be conducted, the patient's ophthalmic report should be reviewed and the dose of Elahere may be modified based on the severity of the findings. Use of lubricating eye drops during treatment with Elahere is recommended. In patients who develop ≥Grade 2 corneal adverse reactions, ophthalmic topical steroids are recommended for subsequent cycles of Elahere. The physician should monitor patients for ocular toxicity and withhold, reduce, or permanently discontinue Elahere based on the severity and persistence of ocular adverse reactions. Patients should be advised to avoid use of contact lenses during treatment with Elahere unless directed by a healthcare professional.

Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with Elahere. Patients should be monitored for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnoea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Elahere treatment should be withheld for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤Grade 1 and dose reduction should be considered. Elahere should be permanently discontinued in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of Elahere with close monitoring. 

Peripheral neuropathy
Peripheral neuropathy has occurred with Elahere, including Grade ≥3 reactions. Patients should be monitored for signs and symptoms of neuropathy, such as paraesthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening peripheral neuropathy, Elahere dose should be withheld, reduced, or permanently discontinued based on the severity of peripheral neuropathy.

Embryo-foetal toxicity
Based on its mechanism of action, Elahere could cause embryo-foetal harm when administered to a pregnant patient because it contains a genotoxic compound (DM4) and affects actively dividing cells. Patients of childbearing potential should use effective contraception during treatment with Elahere and for 7 months after the last dose.

Fertility, pregnancy and lactation
The pregnancy status in patients of childbearing potential should be verified prior to initiating Elahere treatment. Administration of Elahere to pregnant patients is not recommended, and patients should be informed of the potential risks to the foetus if they become or wish to become pregnant. Patients who become pregnant must immediately contact their doctor. If a patient becomes pregnant during treatment with Elahere or within 7 months following the last dose, close monitoring is recommended. It is unknown whether Elahere or its metabolites are excreted in human milk. Elahere should not be used during breast-feeding and for 1 month after the last dose.

Effects on ability to drive and use machines
Elahere has moderate influence on the ability to drive and use machines. If patients experience visual disturbances, peripheral neuropathy, fatigue, or dizziness during treatment with Elahere, they should be instructed not to drive or use machines until complete resolution of symptoms is confirmed. 

Undesirable effects
Summary of safety profile
The most common adverse reactions with Elahere were blurred vision (43%), nausea (41%), diarrhoea (39%), fatigue (35%), abdominal pain (30%), keratopathy (29%), dry eye (27%), constipation (26%), vomiting (23%), decreased appetite (22%), peripheral neuropathy (20%), headache (19%), asthenia (18%), AST increased (16%), and arthralgia (16%). The most commonly reported serious adverse reactions were pneumonitis (4%), small intestinal obstruction (3%), intestinal obstruction (3%), pleural effusion (2%), abdominal pain (2%), dehydration (1%), constipation (1%), nausea (1%), and ascites (1%), and thrombocytopenia (<1%). Adverse reactions that most commonly led to dose reduction or dose delay were blurred vision (17%), keratopathy (10%), dry eye (5%), neutropenia (5%), keratitis (4%), cataract (3%), visual acuity reduced (3%), thrombocytopenia (3%), peripheral neuropathy (3%), and pneumonitis (3%). Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received Elahere, including most commonly, gastrointestinal disorders (4%), respiratory, thoracic, and mediastinal disorders (3%), blood and lymphatic system disorders (1%), nervous system disorders (1%), and eye disorders (1%).

This is not a complete summary of all safety information.
See Elahere^® full Summary of Product Characteristics (SmPC) at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities and biology interventions, including small molecule therapeutics, antibody-drug conjugates (ADCs), Immuno-Oncology-based therapeutics, multi-specific antibody and in situ CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.

Today, our expansive oncology portfolio comprises approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

ⁱ WHO International Agency for Research on Cancer. GLOBOCAN 2022. Cancer Today. Absolute numbers, Mortality, Females, age [0-74], in 2022. Continents. Available here.
ⁱⁱ L.C. Hanker, S. Loibl, N. Burchardi, J. Pfisterer, W. Meier, E. Pujade-Lauraine, I. Ray-Coquard, J. Sehouli, P. Harter, A. du Bois,. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy, Annals of Oncology, Volume 23, Issue 10, 2012.
ⁱⁱⁱ Lee, YC. et al. 2022. Int J Gynecol Cancer;32(6).
^iv Markert S, Lassmann S, Gabriel B, et al. Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue. Anticancer Res. 2008;28(6A):3567–3572.

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