Sio Gene Therapies Announces Positive Six-Month Follow-Up Data from Low-Dose Cohort of Phase 1/2 Trial of AXO-AAV-GM1 for GM...
December 15 2020 - 4:01PM
Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company
focused on developing gene therapies to radically improve the lives
of patients with neurodegenerative diseases, today reported
positive six-month follow-up data from the low-dose cohort
(1.5x1013 vg/kg) of the Company’s dose escalation study of
AXO-AAV-GM1, its adeno-associated viral vector (AAV)9-based gene
therapy candidate for the treatment of GM1 gangliosidosis. Initial
data from the ongoing Phase 1/2 study in five patients in the
low-dose cohort showed that AXO-AAV-GM1 was generally well
tolerated with a favorable safety profile and provide early
indications of clinical disease stability.
“We are excited to report encouraging safety, tolerability,
biomarker, and preliminary efficacy data for AXO-AAV-GM1, the first
gene therapy evaluated in a clinical trial for GM1 gangliosidosis,
a life-limiting disease caused by mutations in the GLB1 gene that
impair beta-galactosidase enzyme activity. Safety was the key
measure in this first-in-human study, and we are pleased to see a
favorable safety profile in the first five children treated with
the low-dose,” said Gavin Corcoran, M.D., Chief R&D Officer of
Sio Gene Therapies. “At this early timepoint post-treatment, we
observed an increase in beta-galactosidase enzymatic activity,
reaching on average 38% of normal reference levels. This is
encouraging given that evidence in the medical literature for
lysosomal storage diseases suggests that increases in enzyme
activity, to between 10-20% of normal levels, can lead to clearance
of stored lysosomal substrates and may be associated with slower
disease progression. We are also encouraged by consistent signs of
disease stabilization across multiple measures of neurodevelopment
in all five children at six months as compared to the predictable
decline observed in natural history studies. These data highlight
the potential for the investigational gene therapy to treat the
underlying genetic cause of this disease, preserve functional
outcomes, and reduce disease burden for patients and their
families. Further, the safety profile observed in the low-dose
cohort support moving forward with the high-dose cohort of
AXO-AAV-GM1 in the ongoing Phase 1/2 study. We look forward to
presenting program updates at future medical conferences.”
Dr. Cynthia Tifft, Deputy Clinical Director of the National
Human Genome Research Institute (NHGRI) added, “I have been
studying and caring for children with GM1 gangliosidosis for more
than 10 years, and I have seen the impact of this relentlessly
progressive, uniformly fatal disease on the children and the heavy
physical and psychological burden on families and caregivers. With
no approved therapies, the treatment options today are limited to
aggressive supportive care with physical, occupational and speech
therapy and later with feeding tubes and anti-convulsants to
minimize seizures. I am encouraged by the results-to-date where we
have seen preservation of function and in a few measures even
improvement. As we advance to the high-dose cohort, I am also
pleased that the side effects of the treatment have been minimal
and easily managed.”
Six-Month Follow-Up Results
Baseline Characteristics:
- Total of 5 Type II patients evaluated: 4 late-infantile onset
patients (aged 32-68 months at time of dosing),
and 1 juvenile onset patient (aged 45 months at time of
dosing).
- All patients had documented biallelic mutations in GLB1 gene,
deficiency of beta-galactosidase enzyme activity, and clinical
phenotype consistent with GM1 gangliosidosis.
- All 5 patients exhibited impairment of fine motor skills and
change in walking pattern on clinical history at baseline.
Safety and Tolerability:
- AXO-AAV-GM1 was generally well-tolerated with a favorable
safety profile at the low dose (1.5x1013 vg/kg) delivered
intravenously.
- There have been no serious adverse events (SAEs) related to
gene therapy.
- One SAE was described: a single patient experienced bacterial
sepsis due to a PICC line infection, which was considered to be
unrelated to the investigational drug product, and which resolved
within a few days following line removal and administration of IV
antibiotics.
- The most common adverse events were considered mild to
moderate. Transient AST elevations were observed in 4 subjects,
none of which required clinical intervention or had associated
clinical sequelae. There were no other adverse events indicative of
impaired liver function including serum bilirubin, GGT, and ALT. No
clinically relevant changes were observed in platelet count.
- The favorable safety profile in the low-dose cohort supports
continued enrollment of patients in the high-dose cohort (4.5x1013
vg/kg), in which two patients have now been dosed without
complications.
Biomarkers:
- Serum beta-galactosidase enzyme activity was sampled at nine
distinct timepoints between Day 7 and Month 6, and increased from
baseline between 71-138% (mean: 110%) during the 6-month
observation period, representing an approximate doubling in enzyme
activity after gene transfer. At Month 6, serum enzyme activity
increased by an average of 71% from baseline (range: 33%-127%)
across the five patients.
- On average, serum enzyme activity was restored to 38% of normal
reference levels at Month 6, with individual patients ranging from
23-57% of normal reference levels. The reference level was defined
by the lowest level of enzyme activity in serum from 30 healthy
adult volunteers using the same validated assay of
beta-galactosidase enzyme activity as was used to assess the
patients in the study.
- Cerebrospinal fluid (CSF) samples were collected from all
patients through lumbar puncture. Development and validation of
biomarker assays for CSF is currently ongoing.
Clinical and Functional Outcomes:
- Patients were assessed by multiple measures of neurodevelopment
including the Vineland Adaptive Behavior Scales 3rd Edition
(VABS-3), Upright and Floor Mobility Score, and Clinical Global
Impression (CGI).
- VABS-3 is a standardized measure of adaptive behavior that is
widely used to evaluate communication, daily living, social skills,
and motor function. VABS-3 scores have a predictable relationship
to ability, allowing for comparative assessments with increasing
age.
- Predictable functional decline in abilities has been well
documented in natural history studies, showing an age-related
statistically significant decline in all sub-domains of the VABS-3
scale and in Floor and Upright Mobility Scores.
- All five patients demonstrated disease stability at 6 months
post-treatment as assessed by VABS-3 Growth Scale Value scores,
Upright and Floor Mobility Score, and CGI relative to baseline
values.
- Subdomain Growth Scale Value scores in the VABS-3 remained
stable or improved in four out of five patients.
- Floor Mobility Scores were scored at the highest level based on
age in all five patients, indicating the ability to crawl in
4-points independently, and remained stable at all timepoints
evaluated over the six-month observation period.
- Upright Mobility Scores were stable in all five patients, with
function maintained at all timepoints evaluated over the 6-month
observation period.
- Clinical Global Impression (CGI), a clinician’s assessment of
change in disease severity from baseline, mildly improved in four
out of five patients and remained stable in the fifth patient over
the six-month evaluation period.
- Additional data will be collected at the 12-month evaluation
including several measures of the systemic manifestations of GM1
gangliosidosis.
The Phase 1/2 study (NCT03952637) is designed to evaluate the
safety, tolerability, and potential efficacy of AXO-AAV-GM1
delivered intravenously in children with Type I and Type II GM1
gangliosidosis. In Stage 1 of the study, the low-dose cohort is
evaluating 1.5x1013 vg/kg AXO-AAV-GM1 gene therapy in a total of
five Type II (late-infantile and juvenile) patients, and the
ongoing high-dose cohort is evaluating a dose of 4.5x1013 vg/kg
AXO-AAV-GM1 gene therapy in both Type I (early infantile) and Type
II children.
About AXO-AAV-GM1
AXO-AAV-GM1 delivers a functional copy of the GLB1 gene via an
adeno-associated viral (AAV) vector, with the goal of restoring
β-galactosidase enzyme activity for the treatment of GM1
gangliosidosis. The gene therapy is delivered intravenously, which
has the potential to broadly transduce the central nervous system
and treat peripheral manifestations of the disease as well.
Preclinical studies in murine and a naturally-occurring feline
model of GM1 gangliosidosis have supported AXO-AAV-GM1’s ability to
improve β-galactosidase enzyme activity, reduce GM1 ganglioside
accumulation, improve neuromuscular function, and extend
survival.
AXO-AAV-GM1 has received both Orphan Drug Designation and Rare
Pediatric Disease Designation from the Food and Drug Administration
and is the only gene therapy in clinical development for both Type
I and Type II GM1 gangliosidosis.
In 2018, Sio licensed exclusive worldwide rights from the
University of Massachusetts Medical School for the development and
commercialization of gene therapy programs for GM1 gangliosidosis
and GM2 gangliosidosis, including Tay-Sachs and Sandhoff
diseases.
About Sio Gene Therapies
Sio Gene Therapies combines cutting-edge science with bold
imagination to develop genetic medicines that aim to radically
improve the lives of patients. Our current pipeline of
clinical-stage candidates includes the first potentially curative
AAV-based gene therapies for GM1 gangliosidosis and
Tay-Sachs/Sandhoff diseases, which are rare and uniformly fatal
pediatric conditions caused by single gene deficiencies. We are
also expanding the reach of gene therapy to highly prevalent
conditions such as Parkinson’s disease, which affects millions of
patients globally. Led by an experienced team of gene therapy
development experts, and supported by collaborations with premier
academic, industry and patient advocacy organizations, Sio is
focused on accelerating its candidates through clinical trials to
liberate patients with debilitating diseases through the
transformational power of gene therapies. For more information,
visit www.siogtx.com.
Forward-Looking Statements
This press release contains forward-looking statements for the
purposes of the safe harbor provisions under The Private Securities
Litigation Reform Act of 1995 and other federal securities laws.
The use of words such as “will,” “expect,” “believe,” “estimate,”
and other similar expressions are intended to identify
forward-looking statements. For example, all statements Sio makes
regarding costs associated with its operating activities are
forward-looking. All forward-looking statements are based on
estimates and assumptions by Sio’s management that, although Sio
believes to be reasonable, are inherently uncertain. All
forward-looking statements are subject to risks and uncertainties
that may cause actual results to differ materially from those that
Sio expected. Such risks and uncertainties include, among others,
the impact of the Covid-19 pandemic on our operations, the
initiation and conduct of preclinical studies and clinical trials;
the availability of data from clinical trials; the development of a
suspension-based manufacturing process for AXO-Lenti-PD; the
scaling up of manufacturing, the expectations for regulatory
submissions and approvals; the continued development of our gene
therapy product candidates and platforms; Sio’s scientific approach
and general development progress; and the availability or
commercial potential of Sio’s product candidates. These statements
are also subject to a number of material risks and uncertainties
that are described in Sio’s most recent Quarterly Report on Form
10-Q filed with the Securities and Exchange Commission on November
13, 2020, as updated by its subsequent filings with the Securities
and Exchange Commission. Any forward-looking statement speaks only
as of the date on which it was made. Sio undertakes no obligation
to publicly update or revise any forward-looking statement, whether
as a result of new information, future events or otherwise.
Contacts:
Media
Josephine Belluardo, Ph.D. LifeSci Communications(646)
751-4361jo@lifescicomms.cominfo@siogtx.com
Investors and Analysts
David NassifSio Gene Therapies Inc.Chief Financial Officer and
General Counsel(646) 677-6770investors@siogtx.com
Sio Gene Therapies (NASDAQ:SIOX)
Historical Stock Chart
From Jun 2024 to Jul 2024
Sio Gene Therapies (NASDAQ:SIOX)
Historical Stock Chart
From Jul 2023 to Jul 2024