Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader,
today announced a range of interim clinical outcomes, in addition
to the previously reported neurological and skeletal results, from
the company’s ongoing proof-of-concept (PoC) study of OTL-203, a
hematopoietic stem cell (HSC) gene therapy in development for the
treatment of the Hurler subtype of mucopolysaccharidosis type I
(MPS-IH). The data were presented at the European Society of Gene
and Cell Therapy (ESGCT) 30th Annual Congress taking place October
24-27, 2023, in Brussels.
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 approximately 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), neither of which effectively address the
broad range of clinical manifestations of the disease.
“These positive data presented at ESGCT add to
the growing body of evidence underscoring the potential of a
one-time HSC gene therapy to correct a range of disease
manifestations not effectively addressed by the current standard of
care,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard
Therapeutics. “The complications associated with MPS-IH involve
multiple organ systems and have an adverse impact on patients’
quality of life. We continue to be encouraged by these results from
our proof-of-concept study and look forward to initiating our
global registrational trial later this year.”
In the single-center 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.
Additional Ocular and Auditory Clinical Data
Presented at ESGCT 2023
At ESGCT, 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), and
auditory (hearing) function. Results showed:
- Treatment with OTL-203 resulted in
improvement (62.5% of patients; n=5/8) or stabilization (37.5% of
patients; n=3/8) of corneal clouding at the time of last follow-up
(ranging from 3.14-4.58 years) compared to baseline measured prior
to administration with OTL-203.
- Importantly, following treatment
with OTL-203, no patients reported photophobia (light sensitivity),
or any other ophthalmological symptoms typically associated with
MPS-IH.
- At last follow-up, 50.0% of
patients (n=4/8) showed normal hearing function, and none developed
severe hearing loss. In addition, no treated patients have required
a hearing aid or any intervention for hearing loss following
administration with OTL-203 as of last follow-up.
- Follow-up to fully assess and
characterize the potential impact of HSC gene therapy on ocular and
auditory manifestations of MPS-IH is ongoing.
Summary of Previously Reported Safety
Results
Treatment with OTL-203 has been generally
well-tolerated with a safety profile consistent with the selected
conditioning regimen. 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. The lentiviral vector integration profile was
consistent with other lentiviral-based HSC gene therapy studies,
and all participants had a stable and highly polyclonal
repertoire.
Global Registrational Trial Expected to Commence
by Year-end
Following the promising results observed in the
proof-of-concept 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
treatment, treatment failure, immunological complications, as well
as severe cognitive and 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, the first of which is
planned to open enrollment later this year.
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 and priority medicines
(PRIME) designations from the FDA and European Medicines Agency,
respectively.
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 (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;
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 Orchard’s products and product candidates.
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 products will not be successfully
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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