SILVER
SPRING, Md., June 20,
2024 /PRNewswire/ -- Today, the U.S. Food and Drug
Administration expanded the approval of Elevidys (delandistrogene
moxeparvovec-rokl), a gene therapy for the treatment of Duchenne
muscular dystrophy (DMD) for ambulatory and non-ambulatory
individuals 4 years of age and older with DMD with a confirmed
mutation in the DMD gene.
Elevidys was previously approved under accelerated approval for
ambulatory individuals 4 through 5 years of age with DMD with a
confirmed mutation in the DMD gene. With today's action,
Elevidys received traditional approval in ambulatory
individuals 4 years of age and older with DMD with a confirmed
mutation in the DMD gene, and accelerated approval in
non-ambulatory individuals 4 years of age and older with DMD with a
confirmed mutation in the DMD gene. In making this decision,
the FDA considered the totality of the evidence, including the
potential risks associated with the product, the life-threatening
and debilitating nature of the disease and the urgent unmet medical
need.
"Today's approval broadens the spectrum of patients with
Duchenne muscular dystrophy eligible for this therapy, helping to
address the ongoing, urgent treatment need for patients with this
devastating and life-threatening disease," said Peter Marks, M.D., Ph.D., director of the FDA's
Center for Biologics Evaluation and Research. "We remain steadfast
in our commitment to help advance safe and effective treatments for
patients who desperately need them."
Duchenne muscular dystrophy is a rare and serious genetic
condition which worsens over time, leading to weakness and wasting
away of the body's muscles. The disease occurs due to a defective
gene that results in abnormalities in, or absence of, dystrophin, a
protein that helps keep the body's muscle cells intact.
As a result of this genetic defect, individuals with DMD may
have symptoms such as trouble walking and running, falling
frequently, fatigue and learning disabilities/difficulties. They
may also experience heart issues as a result of the impact on heart
muscle function and breathing problems due to weakening of
respiratory muscles involved in lung function. Symptoms of muscle
weakness associated with DMD typically begin in childhood, often
between 3 to 6 years of age.
DMD mainly affects males and in rare cases may affect females.
About one in every 3,300 boys are affected by this disorder. As the
disease progresses, life-threatening heart and respiratory problems
can occur. Although disease severity and life expectancy vary,
patients often succumb to the disease in their 20s or 30s because
of heart and/or respiratory failure.
Elevidys is a recombinant gene therapy designed to deliver into
the body a gene that leads to production of Elevidys
micro-dystrophin, a shortened protein (138 kDa, compared to the 427
kDa dystrophin protein of normal muscle cells) that contains
selected domains of the dystrophin protein present in normal muscle
cells. The product is administered as a single intravenous
dose.
Elevidys was initially approved in June
2023 through the Accelerated Approval pathway, under
which the FDA may approve drugs for serious or life-threatening
diseases where there is an unmet medical need and the drug is shown
to have an effect on a surrogate endpoint that is reasonably likely
to predict clinical benefit to patients (improving how patients
feel or function, or whether they survive longer), or an effect on
a clinical endpoint that can be measured earlier than irreversible
morbidity or mortality that is reasonably likely to predict an
effect on irreversible morbidity or mortality or other clinical
benefit. This pathway can allow earlier approval, while the company
conducts clinical trials to verify the predicted clinical
benefit.
Data Supporting Traditional Approval
The FDA granted today's approval based on an evaluation of data
submitted by the sponsor. The efficacy of Elevidys was evaluated in
two double-blind, placebo-controlled studies and two open-label
studies, which enrolled a total of 218 male patients (including
those who received placebo) with a confirmed disease-causing
mutation in the DMD gene.
In one of the studies, the efficacy outcome measures were to
evaluate expression of micro-dystrophin in skeletal muscle, and to
evaluate the effect of Elevidys on the total score of patients on
the North Star Ambulatory Assessment (NSAA) — a scale commonly used
to rate the motor function in males with DMD who are capable of
walking. In another study, the primary efficacy outcome measure was
to evaluate the effect of Elevidys on physical function as assessed
by the NSAA total score. Key secondary outcome measures were to
evaluate expression of micro-dystrophin in skeletal muscle, time to
rise from floor and time of 10-meter walk/run. Additional efficacy
outcome measures included time of 100-meter walk/run and time to
ascend four steps.
While the large, randomized study of Elevidys failed to meet its
statistical primary endpoint of improvement versus placebo in the
NSAA, the FDA found the observations regarding the secondary
endpoints and exploratory endpoints to be compelling and to
indicate clinical benefit compared to placebo. These endpoints
include improvements in time to rise from the floor, 10-meter
walk/run, time to ascend four steps and creatine kinase levels.
Based on the totality of the evidence, the FDA determined the
available evidence verifies the product's clinical benefit for its
original indication, which was initially approved in June 2023 under accelerated approval, and
provides substantial evidence of effectiveness to support
traditional approval of Elevidys in ambulatory individuals 4 years
of age and older with a confirmed mutation in the DMD gene
except in those with any deletion in exon 8 and/or exon 9 in the
DMD gene, in whom its use is contraindicated. An inadequate
amount of safety data is available currently to support the use of
Elevidys in individuals under 4 years of age.
Data Supporting Accelerated Approval
In granting accelerated approval for non-ambulatory individuals
aged 4 and older, the FDA considered the totality of the evidence,
including clinical data in ambulatory individuals from a study in
4- to 7-year-olds, as well as from a study in 4- to 5-year-olds
indicating a correlation of Elevidys micro-dystrophin levels with
clinical outcome measures. Based on the evidence and given that the
mechanism of action of Elevidys is similar for ambulatory and
non-ambulatory populations, the FDA determined that increased
levels in micro-dystrophin is reasonably likely to predict clinical
benefit in the non-ambulatory population. This conclusion, along
with the evidence that Elevidys elevates micro-dystrophin levels,
provides substantial evidence of effectiveness to support
accelerated approval in non-ambulatory individuals at least 4 years
of age with DMD considering the serious nature of the disease and
the extent of unmet medical need in this group of individuals. A
confirmatory randomized, controlled clinical trial in the
non-ambulatory population is currently underway.
The safety of Elevidys was established based on evaluation of
156 male patients with a confirmed mutation of the DMD gene
who received the product in four clinical studies, including one
completed open-label study, one ongoing open-label study, and two
studies that included a double-blind, placebo-controlled period. No
new safety concerns appear to have been identified in the
population of ambulatory individuals treated with the marketed
product. A modest amount of safety data on non-ambulatory
individuals was submitted in the context of an ongoing randomized
clinical trial; safety data in non-ambulatory individuals is
limited, given the number of non-ambulatory individuals included in
the trial and treated with the marketed product to date.
The most commonly reported side effects by individuals who
received Elevidys were vomiting, nausea, acute liver injury, fever
and thrombocytopenia (abnormally low platelet count in the blood).
Patients' liver function should be monitored before treatment with
Elevidys, and weekly for the first three months after treatment.
Patients given Elevidys may also be at risk for severe
immune-mediated myositis (muscle inflammation). Additionally,
myocarditis (inflammation of heart muscle) and elevations of
troponin-I (a heart protein found in the blood after heart muscle
injury) have been observed following use of Elevidys in clinical
trials. Troponin-I levels should be monitored before administration
of Elevidys and weekly for the first month after
treatment.
The FDA granted the approval and accelerated approval for
Elevidys to Sarepta Therapeutics Inc.
Additional Resources:
- ELEVIDYS | FDA
- Package Insert
- FDA Approves First Gene Therapy for Treatment of Certain
Patients with Duchenne Muscular Dystrophy
Media Contact: Carly
Pflaum, 240-672-887
Consumer Inquiries: Email, 888-INFO-FDA
The FDA, an agency within the U.S. Department
of Health and Human Services, protects the public health by
assuring the safety, effectiveness, and security of human and
veterinary drugs, vaccines and other biological products for human
use, and medical devices. The agency also is responsible for the
safety and security of our nation's food supply, cosmetics, dietary
supplements, radiation-emitting electronic products, and for
regulating tobacco products.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/fda-expands-approval-of-gene-therapy-for-patients-with-duchenne-muscular-dystrophy-302178532.html
SOURCE U.S. Food and Drug Administration