- The full
approval of ELAHERE is based on the confirmatory MIRASOL Phase 3
trial that supports the medicine as a potential new standard of
care for folate receptor alpha (FRα)-positive, platinum-resistant
ovarian cancer (PROC)
- Data show that
ELAHERE treatment resulted in an overall survival benefit and
reduced the risk of cancer progression by 35%
- ELAHERE represents
AbbVie's first approved solid tumor treatment following the recent
acquisition of ImmunoGen
NORTH
CHICAGO, Ill., March 22,
2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the U.S. Food and Drug Administration (FDA) has
granted full approval for ELAHERE® (mirvetuximab
soravtansine-gynx) for the treatment of folate receptor alpha
(FRα)-positive, platinum-resistant epithelial ovarian, fallopian
tube or primary peritoneal adult cancer patients treated with up to
three prior therapies. Patients with these cancers often present
with late-stage disease, undergo surgery and are then treated with
platinum-based chemotherapy. They may become resistant to this
treatment and require another therapy, such as ELAHERE.
"The full FDA approval of ELAHERE for eligible patients
with ovarian cancer represents the culmination of years of work by
the ImmunoGen team. ELAHERE is the first and only antibody-drug
conjugate (ADC) approved in the U.S. for this difficult-to-treat
malignancy," said Roopal Thakkar,
M.D., senior vice president, chief medical officer, global
therapeutics, AbbVie.
ELAHERE was first granted
FDA accelerated
approval in November 2022 and the
conversion to full approval is based on data from the confirmatory
Phase 3 MIRASOL trial. This trial compared ELAHERE to
investigator's choice (IC) of chemotherapy in patients with
platinum-resistant ovarian cancer (PROC) whose tumors express high
levels of FRα and who have been treated with up to three prior
therapies. The primary endpoint of MIRASOL was progression-free
survival (PFS) by investigator assessment and key secondary
endpoints included objective response rate (ORR) and overall
survival (OS).
"As the first treatment to show a statistically
significant overall survival benefit in patients with
platinum-resistant ovarian cancer, ELAHERE provides an effective
new option for patients with folate receptor alpha positive tumors.
These patients previously had very limited options and ELAHERE
changes that," said Kathleen Moore,
deputy director and associate director of clinical research at the
Stephenson Cancer Center of The University of
Oklahoma and MIRASOL principal investigator.
ABOUT THE PHASE 3 MIRASOL
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.
Based on current results:
- OS 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.
- PFS 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.
ABOUT OVARIAN CANCER
Ovarian cancer
is the leading cause of death from gynecological cancers in
the United States. Each year,
approximately 20,000 patients are diagnosed. Most patients present
with late-stage disease and will typically undergo surgery followed
by platinum-based chemotherapy. Unfortunately, the majority of
patients eventually develop platinum-resistant disease, which is
difficult to treat. In this setting, standard of care single-agent
chemotherapies are associated with low response rates, short
durations of response, and significant toxicities.
ABOUT ELAHERE
ELAHERE (mirvetuximab
soravtansine-gynx) is a first-in-class ADC comprising a folate
receptor alpha-binding antibody, cleavable linker, and the
maytansinoid payload DM4, a potent tubulin inhibitor designed to
kill the targeted cancer cells. Patients requiring access support
may call 1-833-ELAHERE or
visit www.elahere.com.
The Marketing Authorization Application (MAA) for ELAHERE
in Europe has been accepted by the European
Medicines Agency (EMA). Regulatory submissions for ELAHERE are
also under review in multiple other countries.
INDICATION
ELAHERE is indicated for
the treatment of adult patients with folate receptor-alpha (FRα)
positive, platinum-resistant epithelial ovarian, fallopian tube, or
primary peritoneal cancer, who have received one to three prior
systemic treatment regimens. Select patients for therapy based on
an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNING: OCULAR TOXICITY
- ELAHERE can cause severe ocular toxicities, including
visual impairment, keratopathy, dry eye, photophobia, eye pain, and
uveitis.
- Conduct an ophthalmic exam including visual acuity and
slit lamp exam prior to initiation of ELAHERE, every other cycle
for the first 8 cycles, and as clinically indicated.
- Administer prophylactic artificial tears and ophthalmic
topical steroids.
- Withhold ELAHERE for ocular toxicities until improvement
and resume at the same or reduced dose.
- Discontinue ELAHERE for Grade 4 ocular
toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including
visual impairment, keratopathy (corneal disorders), dry eye,
photophobia, eye pain, and uveitis.
Ocular adverse reactions occurred in 59% of patients with
ovarian cancer treated with ELAHERE. Eleven percent (11%) of
patients experienced Grade 3 ocular adverse reactions, including
blurred vision, keratopathy (corneal disorders), dry eye, cataract,
photophobia, and eye pain; two patients (0.3%) experienced Grade 4
events (keratopathy and cataract). The most common (≥5%) ocular
adverse reactions were blurred vision (48%), keratopathy (36%), dry
eye (27%), cataract (16%), photophobia (14%), and eye pain
(10%).
The median time to onset for first ocular adverse reaction was
5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced
ocular events, 53% had complete resolution; 38% had partial
improvement (defined as a decrease in severity by one or more
grades from the worst grade at last follow up). Ocular adverse
reactions led to permanent discontinuation of ELAHERE in 1% of
patients.
Premedication and use of lubricating and ophthalmic topical
steroid eye drops during treatment with ELAHERE are recommended.
Advise patients to avoid use of contact lenses during treatment
with ELAHERE unless directed by a healthcare provider.
Refer patients to an eye care professional for an ophthalmic
exam including visual acuity and slit lamp exam prior to treatment
initiation, every other cycle for the first 8 cycles, and as
clinically indicated. Promptly refer patients to an eye care
professional for any new or worsening ocular signs and
symptoms.
Monitor for ocular toxicity and withhold, reduce, or permanently
discontinue ELAHERE based on severity and persistence of ocular
adverse reactions.
Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease
(ILD), including pneumonitis, can occur in patients treated with
ELAHERE.
Pneumonitis occurred in 10% of patients treated with ELAHERE,
including 1% with Grade 3 events and 1 patient (0.1%) with a Grade
4 event. One patient (0.1%) died due to respiratory failure in the
setting of pneumonitis and lung metastases. One patient (0.1%) died
due to respiratory failure of unknown etiology. Pneumonitis led to
permanent discontinuation of ELAHERE in 3% of patients.
Monitor patients for pulmonary signs and symptoms of
pneumonitis, which may include hypoxia, cough, dyspnea, or
interstitial infiltrates on radiologic exams. Infectious,
neoplastic, and other causes for such symptoms should be excluded
through appropriate investigations. Withhold ELAHERE for patients
who develop persistent or recurrent Grade 2 pneumonitis until
symptoms resolve to ≤ Grade 1 and consider dose reduction.
Permanently discontinue ELAHERE in all patients with Grade 3 or 4
pneumonitis. Patients who are asymptomatic may continue dosing of
ELAHERE with close monitoring.
Peripheral Neuropathy (PN)
Peripheral neuropathy occurred in 36% of patients with ovarian
cancer treated with ELAHERE across clinical trials; 3% of patients
experienced Grade 3 peripheral neuropathy. Peripheral neuropathy
adverse reactions included peripheral neuropathy (20%), peripheral
sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%),
hypoaesthesia (1%), peripheral motor neuropathy (0.9%),
polyneuropathy (0.3%), and peripheral sensorimotor neuropathy
(0.1%). Monitor patients for signs and symptoms of neuropathy, such
as paresthesia, tingling or a burning sensation, neuropathic pain,
muscle weakness, or dysesthesia. For patients experiencing
new or worsening PN, withhold dosage, dose reduce, or permanently
discontinue ELAHERE based on the severity of PN.
Embryo-Fetal Toxicity
Based on its mechanism of action, ELAHERE can cause embryo-fetal
harm when administered to a pregnant woman because it contains a
genotoxic compound (DM4) and affects actively dividing cells.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment with ELAHERE and for 7 months after the last
dose.
ADVERSE REACTIONS
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.
DRUG INTERACTIONS
DM4 is a CYP3A4 substrate. Closely monitor patients for adverse
reactions with ELAHERE when used concomitantly with strong CYP3A4
inhibitors.
USE IN SPECIAL POPULATIONS
Lactation
Advise women not to breastfeed during
treatment with ELAHERE and for 1 month after the last dose.
Hepatic Impairment
Avoid use of ELAHERE in patients
with moderate or severe hepatic impairment (total bilirubin >1.5
ULN).
Please see full Prescribing Information, including BOXED
WARNING
About AbbVie in Oncology
At AbbVie, we are committed
to transforming standards of care for multiple blood cancers while
advancing a dynamic pipeline of investigational therapies across a
range of cancer types. Our dedicated and experienced team joins
forces with innovative partners to accelerate the delivery of
potential breakthrough medicines. We are evaluating more than 20
investigational medicines in over 300 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
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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
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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.
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