Orchard Therapeutics, recently acquired by Kyowa Kirin with the
goal of accelerating the delivery of new gene therapies to patients
around the globe, today announced a number of updates pertaining to
the advancement of universal newborn screening (NBS) for
metachromatic leukodystrophy (MLD).
NBS is widely considered one of the most
successful public health programs worldwide. In the U.S.,
approximately 1 in 500 newborns have a condition that can be
diagnosed through NBS, and more than 8,000 infants have the
potential to receive life-saving treatment due to this public
health program annually.i
MLD is an ultra-rare, rapidly progressive,
irreversible and ultimately fatal neurometabolic disease that
affects approximately one in 100,000 live births. It is caused by
an error in the gene responsible for encoding the enzyme
arylsulfatase A (ARSA) leading to neurological damage and
developmental regression. In the most severe form of MLD, babies
develop normally but in late infancy start to rapidly lose the
ability to walk, talk and interact with the world around them.
These children eventually deteriorate into a vegetative state,
which may require 24-hour intensive care, and the majority pass
away within five years of symptom onset, creating an enormous
emotional and financial burden on the family.
Recently, the U.S. Food and Drug Administration
(FDA) approved the first and only treatment for eligible children
with early-onset MLD which is marketed by Orchard Therapeutics. The
same treatment has previously been approved by the European
Commission (EC), UK Medicines and Healthcare products Regulatory
Agency (MHRA), and Swiss Agency for Therapeutic Products
(Swissmedic).
“Building on foundational work to establish a
method for identifying MLD through newborn screening, there has
been tremendous progress over the past few years to advance
screening efforts around the world,” said Leslie Meltzer, Ph.D.,
chief medical officer of Orchard Therapeutics. “As with many rare,
life-threatening diseases, early detection and diagnosis is key to
ensuring the best possible outcomes for patients. We recognize the
valuable contributions of researchers, physicians, patient
advocates and families to help ensure the pace of newborn screening
coincides with biomedical innovation, and we look forward to
continuing to support the efforts of the broader community to
accelerate MLD NBS globally.”
Nomination to add MLD to the U.S.
Recommended Uniform Screening Panel submitted by multi-disciplinary
expert working group
A multi-disciplinary expert working group of
advocates, clinicians, public health professionals, and scientists
from the MLD community has submitted a nomination to add MLD to the
U.S. Recommended Uniform Screening Panel (RUSP), a national
guideline comprising a list of medical conditions for which the
federal government recommends all newborns are screened for at
birth. States use the RUSP to inform decisions about which
conditions to include in their respective NBS panels.
The nomination was submitted on June 27 to the
Advisory Committee on Heritable Disorders in Newborns and Children
(ACHDNC), part of the Health Resources and Services Administration
(HRSA) within the U.S. Department of Health and Human Services
(HHS). The submission of the nomination initiates the review
process during which the committee will analyze the evidence
presented about the benefit of NBS for MLD. Considerations will
include the availability of an effective and precise screening test
to detect newborns with the condition, the potential to treat
eligible children with confirmed diagnoses of MLD, and the clinical
utility of pre-symptomatic diagnosis. Once a new condition is added
to the RUSP, adoption and implementation is then carried out at the
state level. As of today, 12 states have RUSP alignment legislation
intended to expedite the process of adding new conditions to state
NBS panels once approved by the HHS Secretary.
A critical element of this process requires
evidence generated by pilot studies. Currently, eleven prospective
investigator-initiated NBS studies for MLD, most of which are
funded by Orchard Therapeutics, are active throughout the U.S.,
Europe and the Middle East, with more than 300,000 newborns
screened to date. Five positive screens have been detected
cumulatively in these studies, all of which resulted in confirmed
diagnoses of MLD. Most recently, a prospective study initiated in
Ospedale Buzzi in Milan, Italy, which will offer NBS for MLD for
babies born in the Lombardy region.
“The submission of the RUSP nomination for MLD
is a monumental step toward implementing newborn screening for this
devastating disease in the U.S.,” said Paul Orchard, M.D., a
pediatric blood and marrow transplant physician at M Health
Fairview and professor in the Division of Pediatric Blood and
Marrow Transplantation and Cellular Therapy Program at the
University of Minnesota Medical School. “Newborn screening on a
broad scale will prove critical for MLD, as it is the only
practical means of identifying patients prior to the onset of
symptoms, which is key to achieving optimal outcomes. I have seen
first-hand the disparity of outcomes for treated versus untreated
children, and I believe we are obligated to provide those with MLD
the best opportunity for a meaningful life through
early diagnosis and intervention.”
Norway becomes the first country in the
world to add MLD to its national newborn screening
program
In addition, following completion of public
consultation, the Ministry of Health and Care Services in Norway
has added MLD to its expanded national NBS panel. This makes Norway
the first country in the world to implement national NBS for
MLD.
“We commend the Norwegian Ministry of Health and
Care Services for recognizing the immense and urgent medical need
and becoming the first country in the world to add MLD to its
national screening program,” said Charlotte Chanson, executive
director of global diagnostics and newborn screening at Orchard
Therapeutics. “We are highly encouraged with the progress advancing
national NBS programs globally and are confident in the strength of
nomination packages given the overwhelming evidence demonstrating
that MLD fulfills the Wilson and Jungner NBS criteria. We look
forward to continuing to support efforts aimed at advancing similar
programs in other European countries.”
Robust package of necessary evidence has
been generated to support the implementation of universal NBS for
MLD
Multiple manuscripts have been published in the
first half of 2024 underscoring the need, feasibility and
cost-effectiveness of newborn screening for MLD. These manuscripts
provide critical evidence demonstrating MLD fulfills the necessary
criteria to be included in national NBS programs. Highlights,
include:
- Consensus guidelines developed by a
panel of MLD experts to establish best practices for the monitoring
and management of metachromatic leukodystrophy in the U.S. were
published in the March 2024 issue of Cytotherapy.
- A real-time Delphi procedure
detailing European consensus-based recommendations for clinical
management for NBS-identified MLD cases were published in the March
2024 edition of the European Journal of Paediatric Neurology.
Consensus-based recommendations for NBS in MLD will enhance
harmonized management and facilitate integration in national
screening programs.
- Findings from a pre-pilot study
conducted in the UK which resulted in the identification of a
late-infantile MLD case. The results, published in the May 2024
issue of Molecular Genetics and Metabolism, add to the growing
compendium of international evidence supporting the need for NBS to
enable early detection and diagnosis of MLD.
- A manuscript published in the May
2024 edition of Molecular Genetics and Metabolism detailing the
high-specificity of the screening assay developed to detect MLD is
precise, ready for deployment, and can be multiplexed with several
other inborn errors of metabolism already tested in NBS centers
worldwide.
- A health economic analysis
demonstrating that newborn screening for MLD is a cost-effective
use of UK’s National Health Service (NHS) resources using a
willingness-to-pay threshold appropriate to the severity of the
disease. The findings, published in the June 2024 International
Journal of Neonatal Screening, support the addition of MLD to the
routine newborn screening program in the country.
Recognizing International Neonatal
Screening Day
The announcement of these updates coincides with
International Neonatal Screening Day, which is observed annually on
June 28 in recognition of the birthday of Dr. Robert Guthrie, a
microbiologist who, in the 1960s, established the filter paper
blood spot card and developed an assay to screen newborns for
phenylketonuria (PKU) in the U.S. His work and advocacy
revolutionized the detection of children with congenital disorders
and spawned modern newborn screening programs around the world.
Orchard Therapeutics is proud to support the
community in its efforts and help generate the data necessary to
enable the implementation of universal NBS for MLD globally.
About MLDMLD is a rare and
life-threatening inherited disease of the body’s metabolic system
estimated to occur in approximately one in every 100,000 live
births based on existing literature. MLD is caused by an error in
the arylsulfatase-A (ARSA) gene that results in the
accumulation of sulfatides in the brain and other areas of the
body, including the liver, gallbladder, kidneys, and/or spleen.
Over time, the nervous system is damaged, leading to neurological
problems such as motor, behavioral and cognitive regression, severe
spasticity and seizures. Patients with MLD gradually lose the
ability to move, talk, swallow, eat and see. In its late infantile
form, mortality at five years from onset is estimated at 50 percent
and 44 percent at 10 years for juvenile patients.ii
About Orchard
TherapeuticsOrchard Therapeutics, a Kyowa Kirin company,
is a global gene therapy leader focused on ending the devastation
caused by genetic and other severe diseases by discovering,
developing, and commercializing new treatments that tap into the
curative potential of hematopoietic stem cell (HSC) gene therapy.
In this approach, a patient’s own blood stem cells are genetically
modified outside of the body and then reinserted, with the goal of
correcting the underlying cause of disease with a single
treatment.
Founded in 2015, Orchard’s roots go back to some
of the first research and clinical developments involving HSC gene
therapy. Our team has played a central role in the evolution of
this technology from a promising scientific idea to a potentially
life-transforming reality. Today, Orchard is advancing a pipeline
of HSC gene therapies designed to address serious diseases where
the burden is immense for patients, families and society and
current treatment options are limited or do not exist.
For more information, please
visit www.orchard-tx.com.
About Kyowa KirinKyowa Kirin
aims to discover novel medicines with life-changing value. As a
Japan-based Global Specialty Pharmaceutical Company, we have
invested in drug discovery and biotechnology innovation for more
than 70 years and are currently working to engineer the next
generation of antibodies and cell and gene therapies with
the potential to help patients affected by a severe or
rare disease. A shared commitment to our values, to sustainable
growth, and to making people smile unites us across our four
regions – Japan, Asia Pacific, North America, and
EMEA/International. You can learn more about the business of Kyowa
Kirin at www.kyowakirin.com.
iGaviglio et. al. Infants with Congenital
Diseases Identified through Newborn Screening—United States,
2018–2020. International Journal of Neonatal Screening. 2023, 9(2),
23; https://doi.org/10.3390/ijns9020023
iiMahmood et. al. Metachromatic Leukodystrophy:
A Case of Triplets with the Late Infantile Variant and a Systematic
Review of the Literature. Journal of Child Neurology. 2010, 25(5),
572-580; http://doi.org/10.1177/0883073809341669
Contact
Benjamin Navon
+1 857-248-9454
Benjamin.Navon@orchard-tx.com