MINT Study Results Show Clinically Meaningful
and Statistically Significant Efficacy in AChR+ and MuSK+
Patients
First and Only Phase 3 Placebo-Controlled gMG
Trial for a Biologic That Tapered Corticosteroid Use
THOUSAND
OAKS, Calif., Oct. 15,
2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced the presentation of positive top-line results from the
Phase 3 MINT trial evaluating the efficacy and safety of
UPLIZNA® (inebilizumab-cdon) for the treatment of adults
with generalized myasthenia gravis (gMG), a rare autoimmune
disorder. Results from this randomized, double-blind,
placebo-controlled, parallel-group trial will be presented at the
Myasthenia Gravis Foundation of America (MGFA) Scientific Session
during the American Association of Neuromuscular &
Electrodiagnostic Medicine (AANEM) Annual Meeting, taking place
Oct. 15-18 in Savannah, Georgia.
The trial met its primary endpoint, with a statistically
significant change from baseline in Myasthenia Gravis Activities of
Daily Living (MG-ADL) score for UPLIZNA (-4.2) compared with
placebo (-2.2) (difference: –1.9, p<0.0001) at Week 26 for the
combined study population. The study included patients who are
acetylcholine receptor autoantibody-positive (AChR+) and those who
are muscle-specific kinase autoantibody-positive (MuSK+), with
participants receiving UPLIZNA or placebo on Day 1 and Day 15.
UPLIZNA demonstrated continued improvement through Week 26.
Notably, patients who entered the study taking corticosteroids were
tapered down starting at Week 4 to prednisone 5 mg per day by Week
24. No new safety signals were identified.
"Patients living with generalized myasthenia gravis
deserve an effective treatment option that provides long-term
symptom relief. Once approved, UPLIZNA is expected to offer a new
option for patients earlier in their treatment plan," said
Jay Bradner, M.D., executive vice
president, Research and Development, and chief scientific officer
at Amgen. "UPLIZNA targets CD19+ pre-B cells, mature B-cells and
some plasmablasts, which are drivers of the disease. The clinically
significant results from the MINT trial further strengthen the
growing evidence for UPLIZNA in severe autoimmune diseases and
reinforce Amgen's leadership in B-cell targeting
therapeutics."
Key secondary endpoints were tested sequentially in a predefined
order. UPLIZNA demonstrated a statistically significant and
clinically meaningful change from baseline compared to placebo for
the first four key secondary endpoints.
- UPLIZNA demonstrated a statistically significant change in
Quantitative Myasthenia Gravis (QMG) score for the combined
population (-4.8) compared to placebo (-2.3) at Week 26
(difference: -2.5, p=0.0002).
- In the AChR+ population, UPLIZNA demonstrated mean change
from baseline (-4.2) in MG-ADL score at Week 26 compared to placebo
(-2.4) (difference: -1.8, p=0.0015).
- In the AChR+ population, UPLIZNA demonstrated mean change
from baseline (-4.4) in QMG score at Week 26 compared to placebo
(-2.0) (difference -2.5, p=0.0011).
- In the MuSK+ population, UPLIZNA demonstrated mean change
from baseline (-3.9) in MG-ADL score at Week 26 compared to placebo
(-1.7) (difference -2.2, p=0.0297).
Additionally, in the MuSK+ population, the mean change from
baseline in QMG score at Week 26 showed a trend favoring UPLIZNA
but was not statistically significant (-5.2 for UPLIZNA and -3.0
for placebo, difference -2.3, p=0.1326).
"Myasthenia gravis can have a profound impact on patients by
causing severe fatigable muscle weakness that impairs physical
functioning, activities of daily living and quality of life," said
Richard J. Nowak, M.D., M.S., global
principal study investigator and director of the Myasthenia Gravis
Clinic at Yale University. "This trial
demonstrates clinically meaningful benefits of UPLIZNA, a
twice-yearly infused medicine with a unique mechanism of action
that selectively targets and depletes CD19+ B cells, which are key
upstream drivers of myasthenia gravis. MINT is also the only Phase
3 biologic trial that included a protocol-specified steroid taper,
an important consideration for patients as effects of prolonged
high-dose steroid use contribute to the overall burden of
disease."
The overall safety results during the placebo-controlled period
of the trial were consistent with the known safety profile of
UPLIZNA. The most common treatment-emergent adverse events were
COVID-19, nasopharyngitis, urinary tract infection, infusion
related reaction, headache and cough in the combined
population.
MINT is the largest placebo-controlled gMG clinical trial for a
biologic therapy (238 adults) and enrolled the largest number of
patients (48 adults) who are MuSK+. The trial also included 190
adults who are AChR+. Further data will characterize
placebo-controlled efficacy and safety of UPLIZNA over 12 months in
AChR+ patients with gMG.
At the 2024 AANEM Annual Meeting, Amgen will also be presenting
a poster titled, "The Burden of Glucocorticoid Use Among Patients
with Generalized Myasthenia Gravis in the
United States," highlighting how higher use of
glucocorticoids was associated with more toxicities and overall
health care resource utilization and costs.
UPLIZNA is currently approved for the treatment of neuromyelitis
optica spectrum disorder (NMOSD) in adult patients who are
anti-aquaporin-4 (AQP4) antibody positive in the United States, European Union,
Brazil and Canada, among other countries. UPLIZNA was
also recently granted Breakthrough Therapy Designation for
IgG4-Related Diseases by FDA following Phase 3 results announced in
June.
Based on the MINT primary results, Amgen is planning
to file for approval in the U.S., followed by other key
markets.
About the MINT Trial
The MINT trial is a randomized,
double-blind, placebo-controlled, parallel-group trial
(NCT04524273) evaluating the efficacy and safety of UPLIZNA in
adults with gMG. The trial enrolled 238 adults with gMG, including
190 patients who are acetylcholine receptor autoantibody-positive
(AChR+) and 48 patients who are muscle-specific kinase
autoantibody-positive (MuSK+).
Eligibility criteria at screening and randomization included a
Myasthenia Gravis Foundation of America (MGFA) classification of
II, III, or IV disease, MG-ADL score between 6 and 10 with greater
than 50% of this score attributed to non-ocular items, or an MG-ADL
score of at least 11, QMG score of at least 11, and use of a
corticosteroid and/or non-steroidal immunosuppressant.
The primary endpoint was change from baseline in MG-ADL score at
Week 26 in the combined population. Key secondary endpoints
included change from baseline in QMG scores in the combined study
population; change from baseline in MG-ADL score at Week 26 for the
AChR+ cohort and separately the MuSK+ cohort; and change from
baseline in QMG score at Week 26 for the AChR+ cohort and
separately the MuSK+ cohort. Patients who entered the study taking
a corticosteroid were tapered down to prednisone 5 mg a day,
starting at Week 4 to Week 24. The MINT trial also includes an
optional three-year open-label treatment period.
About Generalized Myasthenia Gravis (gMG)
Generalized
myasthenia gravis (gMG) is a rare, chronic, B-cell-mediated
autoimmune disorder that impairs neuromuscular communication and
can cause muscle weakness, trouble breathing, difficulty swallowing
and impaired speech and vision.1-4 Approximately 85% of
patients with myasthenia gravis have the generalized form, or
gMG.4,5
The prevalence and incidence of gMG are increasing
worldwide.5 There are between 80,000 and 100,000
patients with myasthenia gravis in the U.S.6,7
Approximately 85% of patients with myasthenia gravis have
detectable antibodies against AChR, and approximately 7% have
detectable antibodies against MuSK.8 Global prevalence
is estimated at 2-36 cases per 100,000.9 The disease is
more frequently seen in young women (age 20-30) and men aged 50
years and older.5,9
B cells are central to the pathogenesis of gMG. The disease is
thought to be primarily driven by pathogenic CD19+ plasmablasts and
plasma cells that target critical proteins in the neuromuscular
junction.1-3
About UPLIZNA® (inebilizumab-cdon) in NMOSD
INDICATION
UPLIZNA® (inebilizumab-cdon) is indicated for the treatment of
neuromyelitis optica spectrum disorder (NMOSD) in adult patients
who are anti-aquaporin-4 (AQP4) antibody positive.
IMPORTANT SAFETY INFORMATION
UPLIZNA is contraindicated in patients with:
- A history of life-threatening infusion reaction
to UPLIZNA
- Active hepatitis B infection
- Active or untreated latent tuberculosis
WARNINGS AND PRECAUTIONS
Infusion Reactions: UPLIZNA can cause infusion
reactions, which can include headache, nausea, somnolence, dyspnea,
fever, myalgia, rash, or other symptoms. Infusion reactions were
most common with the first infusion but were also observed during
subsequent infusions. Administer pre-medication with a
corticosteroid, an antihistamine, and an anti-pyretic.
Infections: The most common infections reported by
UPLIZNA-treated patients in the randomized and open-label periods
included urinary tract infection (20%), nasopharyngitis (13%),
upper respiratory tract infection (8%), and influenza (7%). Delay
UPLIZNA administration in patients with an active infection until
the infection is resolved.
Increased immunosuppressive effects are possible if combining
UPLIZNA with another immunosuppressive therapy.
The risk of Hepatitis B Virus (HBV) reactivation has been
observed with other B-cell-depleting antibodies. Perform HBV
screening in all patients before initiation of treatment with
UPLIZNA. Do not administer to patients with active hepatitis.
Although no confirmed cases of Progressive Multifocal
Leukoencephalopathy (PML) were identified in UPLIZNA clinical
trials, JC virus infection resulting in PML has been observed in
patients treated with other B-cell-depleting antibodies and other
therapies that affect immune competence. At the first sign or
symptom suggestive of PML, withhold UPLIZNA and perform an
appropriate diagnostic evaluation.
Patients should be evaluated for tuberculosis risk factors and
tested for latent infection prior to initiating UPLIZNA.
Vaccination with live-attenuated or live vaccines is not
recommended during treatment and after discontinuation, until
B-cell repletion.
Reduction in Immunoglobulins: There may be a
progressive and prolonged hypogammaglobulinemia or decline in the
levels of total and individual immunoglobulins such as
immunoglobulins G and M (IgG and IgM) with continued UPLIZNA
treatment. Monitor the level of immunoglobulins at the beginning,
during, and after discontinuation of treatment with UPLIZNA until
B-cell repletion especially in patients with opportunistic or
recurrent infections.
Fetal Risk: May cause fetal harm based on animal data.
Advise females of reproductive potential of the potential risk to a
fetus and to use an effective method of contraception during
treatment and for 6 months after stopping UPLIZNA.
Adverse Reactions: The most common adverse reactions (at
least 10% of patients treated with UPLIZNA and greater than
placebo) were urinary tract infection and arthralgia.
For additional information on UPLIZNA, please see the Full
Prescribing Information at www.UPLIZNA.com.
About Amgen
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