Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader,
today announced the U.S. Food and Drug Administration (FDA) has
granted Fast Track designation to OTL-203, an investigational
hematopoietic stem cell gene (HSC) therapy being developed for the
potential treatment of the Hurler subtype of mucopolysaccharidosis
type I (MPS-IH). Fast Track designation is intended to expedite the
development of promising medicines that address serious medical
needs. Therapeutic candidates that receive Fast Track designation
may be eligible for enhanced interactions with the FDA, including
potentially quicker submission and review timelines.
MPS-I is a rare, inherited neurometabolic
disease caused by a deficiency of the alpha-L-iduronidase (IDUA)
lysosomal enzyme resulting in the accumulation of
glycosaminoglycans (GAGs) in multiple organs, including the eyes,
ears, heart, as well as the musculoskeletal and central nervous
systems. It is estimated to occur globally in 1 in 100,000 live
births. Approximately 60 percent of children born with MPS-I have
the most severe subtype, MPS-IH, also called Hurler syndrome, and
rarely live past the age of 10 when untreated. Current treatment
options for MPS-IH include allogeneic hematopoietic stem cell
transplant (HSCT) and chronic enzyme replacement therapy (ERT),
both of which have significant limitations.
“At Orchard Therapeutics, we are applying our
HSC gene therapy platform to indications where we believe it is
clinically differentiated and has the greatest potential to make a
paradigm-shifting impact on the treatment landscape,” said Leslie
Meltzer, Ph.D., chief medical officer. “We are encouraged that
OTL-203 has been granted Fast Track designation because new
treatment options are urgently needed for children with MPS-IH, as
the current standard of care is associated with significant
morbidity and mortality. Moreover, existing treatment options do
not adequately address the broad range of clinical manifestations
of the disease, including those that are most burdensome and have a
high impact on quality of life. We look forward to initiating our
global registrational trial in December to evaluate the efficacy
and safety of OTL-203 compared to allogeneic HSCT.”
OTL-203 has previously received Rare Pediatric
Disease (RPD) and priority medicines (PRIME) designations from the
FDA and European Medicines Agency, respectively.
Summary of the Clinical Development
Program for OTL-203
In an ongoing single-center proof-of-concept
(PoC) study, eight patients diagnosed with MPS-IH were treated at
Ospedale San Raffaele in Milan, Italy with investigational OTL-203
between July 2018 and December 2019. Interim results published in
The New England Journal of Medicine showed all patients had stable
cognitive performance post-treatment. In addition, all participants
had progressed along expected growth percentiles of healthy
children and exhibited longitudinal growth that was considered
within the normal range adjusted for age and gender. In subsequent
follow-up, study investigators have observed continued cognitive
development and evidence of continued growth within normal range
and improvements in skeletal health with a median follow-up of 3.78
years (range: 3.14 to 4.58 years) as of May 2023.
In addition to the biochemical, neurological and
skeletal results previously reported, last month at the European
Society of Cell and Gene Therapy (ESGCT) 30th Annual Congress, Dr.
Maria Ester Bernardo, clinical coordinator, pediatric clinical
research unit at San Raffaele Telethon-Institute for Gene Therapy
(SR-TIGET) and the principal investigator of the PoC study,
detailed the first findings on other treatment outcomes, including
ocular (eye) symptoms and auditory (hearing) function. Results
showed favorable results for disease manifestations not effectively
addressed by the current standard of care and further highlights
the ability of gene modified HSCs to migrate into and correct
abnormalities in multiple different tissues and organs.
Throughout the PoC study, treatment with OTL-203
has been generally well-tolerated with a safety profile consistent
with the selected conditioning regimen. The viral vector
integration profile was consistent with other lentiviral-based HSC
gene therapy studies, and all participants had a stable and highly
polyclonal repertoire. Anti-alpha-L-iduronidase (IDUA) antibodies
present prior to gene therapy as a result of ERT were not seen in
any patient within two months following treatment. In addition, ERT
was discontinued at least three weeks prior to any patient
receiving gene therapy treatment, and no patients have re-started
ERT post-treatment.
Global Registrational Trial Expected to
Commence by Year-end
Following the promising results observed in the
PoC study, Orchard Therapeutics is initiating a multi-center,
randomized, active controlled clinical trial designed to evaluate
the efficacy and safety of OTL-203 in patients with MPS-IH compared
to standard of care with allogeneic HSCT. A total of 40 patients
with a confirmed diagnosis of MPS-IH who meet the study inclusion
criteria will be randomized 1:1 to receive either OTL-203 or
allogeneic HSCT. The study is powered to demonstrate superiority of
OTL-203 over HSCT.
The primary endpoint, which will be measured at
two years post-treatment, comprises a composite of clinically
meaningful outcomes, including death, the need for rescue
transplant, treatment failure, immunological complications, as well
as severe cognitive and/or growth impairment. Secondary endpoints
include biochemical markers, additional clinical assessments, as
well as safety and tolerability. The company expects to activate up
to six sites in the United States and Europe. For more information,
please visit www.clinicaltrials.gov (NCT06149403).
About
MPS-IMucopolysaccharidosis type I (MPS-I) is a rare,
inherited neurometabolic disease caused by a deficiency of the
alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to
break down sugar molecules called glycosaminoglycans (GAGs). The
accumulation of GAGs across multiple organ systems results in
multiple symptomatic manifestations of the disease including severe
neurocognitive impairment, skeletal deformities, cardiovascular and
pulmonary complications, impaired motor function, loss of hearing
and corneal clouding. MPS-I occurs at an overall estimated
frequency of one in every 100,000 live births. There are three
subtypes of MPS-I. Approximately 60 percent of children born with
MPS-I have the most severe subtype, called Hurler syndrome
(MPS-IH), and rarely live past the age of 10 when untreated.
Treatment options for MPS-I include
hematopoietic stem cell transplant and chronic enzyme replacement
therapy, both of which have limitations, such as inadequate impact
on some of the more severe manifestations of disease, as well as
significant morbidity and mortality. At present, Newborn Screening
(NBS) for MPS-I has been established in multiple geographies,
including the United States and Europe.
About OTL-203OTL-203 is an
investigational hematopoietic stem cell gene therapy being
developed for the treatment of MPS-IH. It uses a modified virus to
insert a functional copy of the IDUA gene into a
patient’s cells. OTL-203 is being developed in partnership with the
San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.
OTL-203 has received Rare Pediatric Disease (RPD) and Fast Track
designations from the U.S. FDA, as well as priority medicines
(PRIME) status from the European Medicines Agency.
About Orchard TherapeuticsAt
Orchard Therapeutics, our vision is to end the devastation caused
by genetic and other severe diseases. We aim to do this 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 in a single
treatment.
In 2018, the company acquired GSK’s rare disease
gene therapy portfolio, which originated from a pioneering
collaboration between GSK and the San Raffaele Telethon Institute
for Gene Therapy in Milan, Italy. Today, Orchard is advancing a
pipeline spanning pre-clinical, clinical and commercial stage 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.
Orchard has its global headquarters
in London and U.S. headquarters in Boston. For
more information, please visit www.orchard-tx.com, and follow
us on X (formerly Twitter) and LinkedIn.
Availability of Other Information About
OrchardInvestors and others should note that Orchard
communicates with its investors and the public using the company
website (www.orchard-tx.com), the investor relations website
(ir.orchard-tx.com), and on social media (X; formerly
Twitter and LinkedIn), including but not limited to
investor presentations and investor fact sheets, U.S.
Securities and Exchange Commission filings, press releases,
public conference calls and webcasts. The information that Orchard
posts on these channels and websites could be deemed to be material
information. As a result, Orchard encourages investors, the media,
and others interested in Orchard to review the information that is
posted on these channels, including the investor relations website,
on a regular basis. This list of channels may be updated from time
to time on Orchard’s investor relations website and may include
additional social media channels. The contents of Orchard’s website
or these channels, or any other website that may be accessed from
its website or these channels, shall not be deemed incorporated by
reference in any filing under the Securities Act of 1933.
Forward-looking StatementsThis
press release contains forward-looking statements, which are made
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. All statements that are not
statements of historical facts are, or may be deemed to be,
forward-looking statements. Forward-looking statements include
express or implied statements relating to, among other things, the
therapeutic potential of OTL-203, the development timeline for
OTL-203, including the timing of clinical trials, and the timing
and likelihood of regulatory approvals for OTL-203. These
statements are neither promises nor guarantees and are subject to a
variety of risks and uncertainties, many of which are beyond
Orchard’s control, which could cause actual results to differ
materially from those contemplated in these forward-looking
statements. In particular, these risks and uncertainties include,
without limitation, the risk that the development of OTL-203 will
be delayed, the risk that OTL-203 will not be successfully approved
or commercialized and the risk that long-term adverse safety
findings may be discovered. Given these uncertainties, the reader
is advised not to place any undue reliance on such forward-looking
statements.
Other risks and uncertainties faced by Orchard
include those identified under the heading "Risk Factors" in
Orchard’s most recent annual or quarterly report filed with the
U.S. Securities and Exchange Commission (SEC), as well as
subsequent filings and reports filed with the SEC. The
forward-looking statements contained in this press release reflect
Orchard’s views as of the date hereof, and Orchard does not assume
and specifically disclaims any obligation to publicly update or
revise any forward-looking statements, whether as a result of new
information, future events or otherwise, except as may be required
by law.
Contact
Benjamin Navon
+1 857-248-9454
Benjamin.Navon@orchard-tx.com
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