Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader,
today announced long-term results from an updated integrated
analysis of 39 patients with metachromatic leukodystrophy (MLD)
treated with investigational OTL-200 in the clinical development
program. The data were presented yesterday at the ongoing Society
for the Study of Inborn Errors of Metabolism (SSIEM) Annual
Symposium in Jerusalem.
“MLD is a devastating and ultimately fatal
disease for which there are no alternative treatment options beyond
supportive care,” said Leslie Meltzer, Ph.D., chief medical officer
of Orchard Therapeutics. “These data, which now encompass more than
a cumulative 250 years of patient experience, continue to show
sustained preservation of cognitive function and motor development
in most patients compared to disease natural history consistent
with previously published results. Moreover, results from the
updated integrated analysis presented at SSIEM are key components
of the clinical package in the OTL-200 BLA we recently submitted to
the FDA.”
Thirty-nine pediatric patients with early-onset
MLD, enrolled in two prospective non-randomized clinical studies
(n=30) or treated under expanded access frameworks (n=9), were
administered OTL-200 and compared with natural history data from 49
untreated patients. All treated patients were administered OTL-200
and subsequently monitored at Ospedale San Raffaele in Milan,
Italy.
The composite endpoint used in the updated
integrated analysis is severe motor impairment-free survival
(sMFS), defined as the interval from birth to the first occurrence
of loss of locomotion and loss of sitting without support (Gross
Motor Function Classification-MLD [GMFC-MLD] Level ≥ 5) or
death.
Importantly, use of sMFS was discussed with the
U.S. Food and Drug Administration (FDA) who agreed it is clinically
meaningful.
At the time of the updated integrated analysis
(median follow-up 6.76 years, range 0.64-12.19 years), results from
treated patients showed:
Efficacy
- Treatment with OTL-200 resulted in
statistically significant and clinically meaningful improvement in
sMFS in the pre-symptomatic late infantile (p<0.001),
pre-symptomatic early juvenile (p=0.042) and early-symptomatic
early juvenile (p<0.001) MLD subgroups compared to disease
natural history.
- Seventeen of 18 pre-symptomatic
late infantile patients maintained the ability to walk at last
assessment (GMFC-MLD Level 2 or better; range of age at last
assessment: 3.2 to 13.4 years), in contrast to untreated late
infantile natural history patients, all of whom lost all locomotion
(GMFC-MLD Level 5 or worse) by a median age of 2.6 years.
- All seven surviving pre-symptomatic
early juvenile patients maintained the ability to walk without
support with quality and performance normal for age at last
assessment (GMFC-MLD Level 0; range of age at last assessment: 2.1
to 11.9 years), and seven of nine surviving early-symptomatic early
juvenile patients maintained the ability to sit without support
and/or crawl/roll at last assessment (GMFC-MLD Level 4 or better;
range of age at last assessment: 5.1 to 19.1 years), in contrast
with untreated early juvenile natural history patients, all of whom
lost all locomotion (GMFC-MLD Level 5 or worse) by a median age of
6.4 years.
- Seventeen of 18 pre-symptomatic
late infantile, all seven surviving pre-symptomatic early juvenile,
and six of nine surviving early-symptomatic early juvenile patients
have continued to acquire cognitive skills as expected for age,
shown by the upward trajectory of performance and verbal
age-equivalents over chronological ages.
- All treated patients had
reconstituted ARSA activity in peripheral blood mononuclear cells
(PBMCs) with geometric mean values within or above normal range by
three months post-treatment and in cerebrospinal fluid by three to
six months post-treatment, which has been sustained throughout
follow-up.
Safety
- With more than a cumulative 250
patient-years of follow-up, treatment with OTL-200 was generally
well-tolerated, with no treatment-related serious adverse events or
deaths. Most adverse events were associated with busulfan
conditioning or background disease. There were three patient deaths
observed in the study, none of which were considered related to
treatment with OTL-200.
- Six treatment-related adverse
events of anti-ARSA antibodies reported, which resolved either
spontaneously or after B-cell depleting therapy with no impact on
clinical outcome. Antibody titers in all cases were generally low
and no negative effects were observed in the engraftment of
gene-corrected cells or in post-treatment ARSA activity.
- Delayed platelet engraftment
occurred in four patients all of which resolved within the first
four months after conditioning with no bleeding events reported.
One patient with a complex medical history and comorbidities
experienced prolonged anemia and thrombocytopenia requiring
infusion of unmanipulated back-up cells and remains in good
clinical condition.
- There have been no cases of
malignancy or insertional oncogenesis and no evidence of clonal
dominance or expansion reported to date, consistent with other
Orchard lentiviral HSC gene therapy studies.
As previously announced, the company has
completed the rolling submission of its Biologics License
Application (BLA) to the U.S. Food and Drug Administration (FDA)
for OTL-200, in children with early-onset MLD. OTL-200 previously
received both Rare Pediatric Disease (RPD) and Regenerative
Medicine Advanced Therapy (RMAT) designations from the FDA. Orchard
Therapeutics has requested priority review, which if granted, would
put OTL-200 on track for a potential U.S. approval in the first
half of 2024.
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 a mutation 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.i
About Libmeldy /
OTL-200Libmeldy (atidarsagene autotemcel), also known as
OTL-200, has been approved by the European Commission for the
treatment of metachromatic leukodystrophy (MLD) in patients
characterized by biallelic mutations in the ARSA gene leading to a
reduction of the ARSA enzymatic activity in children with i) late
infantile or early juvenile forms, without clinical manifestations
of the disease, or ii) the early juvenile form, with early clinical
manifestations of the disease, who still have the ability to walk
independently and before the onset of cognitive decline. Libmeldy
is the first therapy approved for eligible patients with
early-onset MLD.
The most common adverse reaction attributed to
treatment with Libmeldy was the occurrence of anti-ARSA antibodies.
In addition to the risks associated with the gene therapy,
treatment with Libmeldy is preceded by other medical interventions,
namely bone marrow harvest or peripheral blood mobilization and
apheresis, followed by myeloablative conditioning, which carry
their own risks. During the clinical studies of Libmeldy, the
safety profiles of these interventions were consistent with their
known safety and tolerability.
For more information about Libmeldy, please see
the Summary of Product Characteristics (SmPC) available on the EMA
website.
Libmeldy is approved in the European Union, UK,
Iceland, Liechtenstein and Norway. OTL-200 is an investigational
therapy in the U.S.
Libmeldy was developed in partnership with the
San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in
Milan, Italy.
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 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
(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. 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 prior results, including signals of safety and efficacy, will
not be replicated or will not continue in ongoing or future studies
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.______________________________iMahmood 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,
DOI: http://doi.org/10.1177/0883073809341669
Contact
Benjamin Navon
+1 857-248-9454
Benjamin.Navon@orchard-tx.com
Orchard Therapeutics (NASDAQ:ORTX)
과거 데이터 주식 차트
부터 4월(4) 2024 으로 5월(5) 2024
Orchard Therapeutics (NASDAQ:ORTX)
과거 데이터 주식 차트
부터 5월(5) 2023 으로 5월(5) 2024