AGTC Announces Robust
Improvements in Visual Sensitivity in Adult and Pediatric Patients, and
Plans to Continue Clinical Development of AGTC-401 in Patients with
CNGB3 Achromatopsia
AGTC-401 demonstrated a favorable safety profile through second-highest dose (1.1E+12 vg/mL) in ACHMB3 pediatric patients
At
the dose of 1.1E+12 vg/mL greater than 50% of the combined adults and
children that received AGTC-401 were responders based on improvements in
visual sensitivity
Totality
of data from adult and pediatric patients indicate biologic activity
and reaffirm previous positive safety findings in adults
Company to host conference call to review data today at 8:00 a.m. ET
GAINESVILLE,
Fla. and CAMBRIDGE, Mass., Feb. 08, 2022 (GLOBE NEWSWIRE) -- Applied
Genetic Technologies Corporation (Nasdaq: AGTC), a clinical stage
biotechnology company focused on the development and commercialization
of adeno-associated virus (AAV)-based gene therapies for the treatment
of rare and debilitating diseases with an initial focus on inherited
retinal diseases, today reported updated interim three-month pediatric
results and additional adult safety results out to as long as 24 months
from its ongoing Phase 1/2 dose escalation study of AGTC-401. AGTC-401
is a recombinant AAV viral vector-based gene therapy targeting mutations
in the CNGB3 gene in patients with achromatopsia (ACHMB3). Data from
seven pediatric patients support previously reported findings from
adults treated with AGTC-401, which demonstrated encouraging biologic
activity and a favorable safety profile. There were no new Suspected
Unexpected Serious Adverse Reactions (SUSARs) and for the three
previously reported SUSARs, the inflammation continues to improve with
steroid treatment. Based on the totality of the ACHMB3 data generated to
date from 31 patients over as long as 24 months, AGTC plans to advance
the clinical development of AGTC-401 subject to consultation with the
U.S. Food and Drug Administration (FDA) at an End-of-Phase 2 (EOP2)
meeting in the first half of 2022.
The Company also reported
updated results from a parallel study of AGTC-402 targeting CNGA3
mutations in patients with achromatopsia that are consistent with
previously reported results in adults, provide no indication of clinical
improvements, and do not support further clinical development. Most
patients with CNGA3 mutations express a mutant protein that is not
typically found in patients with CNGB3 mutations, which the Company
believes may have impacted results seen in patients that received
AGTC-402. AGTC will continue to follow the ACHMA3 patients for long-term
safety observations.
“The three-month pediatric findings
provide further evidence for the strong potential of our product
candidate for patients with ACHMB3, and we look forward to continuing
our discussions with the regulatory agencies to determine the best path
forward to bring this important therapy to patients,” said Sue Washer,
President and Chief Executive Officer of AGTC. “We understand the
challenges that patients with achromatopsia face in their daily lives
and our team remains dedicated to advancing this program toward
commercialization. These additional data provide us the opportunity to
help inform the next phase of clinical development and we thank the
patients and investigators for their participation in this important
clinical trial.”
In the Phase 1/2 dose escalation study of
AGTC-401 in ACHMB3 patients, a total of 21 adults were treated over a
100-fold dose range in five groups and a total of ten pediatric patients
were treated at the three highest dose groups. The primary purpose of
any Phase1/2 clinical trial is to identify a well-tolerated dose that
provides clinical benefit to patients. The Company believes that the
data to date support that the 1.1E+12vg/mL dose is well tolerated and
provides clinical benefit in both adult and pediatric patients.
“We’re
pleased to have identified a generally safe and well tolerated dose of
AGTC-401 for both adults and pediatric patients when inflammation is
controlled,” said Dr. Robert Sisk, MD, Director of Pediatric
Vitreoretinal Surgery and Director of Ophthalmic Genetics – Cincinnati
Children’s Hospital and the Cincinnati Eye Institute and an investigator
in the ongoing AGTC achromatopsia Phase 1/2 trials. “Based on the
available pediatric data at three months, which are consistent with
previously reported results in adults with ACHMB3, we are encouraged by
the biologic activity observed in patients treated with AGTC-401. The
achromatopsia community currently faces a significant unmet need and the
totality of this data reinforces the promise of AGTC-401 as a potential
treatment option if confirmed in future studies.”
As previously
reported, in both the ACHMB3 and ACHMA3 trials, treatment with the
highest doses of AGTC-401 and AGTC-402, respectively, led to three cases
of severe ocular inflammation in pediatric patients, which were
reported as SUSARs. No new additional SUSARs have been reported and the
inflammation in all previously reported SUSARs improved with an adjusted
steroid regimen. Two SUSARs (one in ACHMA3 and one in ACHMB3) have
since fully resolved and one (ACHMA3) continues to resolve, with all
three patients’ best corrected visual acuity returning to baseline.
Secondary
outcome measures evaluating efficacy were assessed by standard visual
function tests such as perimetry. We defined two pediatric patients (17
and 7 years old) in the 1.1E+12 vg/mL dose group as responders based on
improvements in visual sensitivity. Therefore, of the three adults and
four children (total n=7) in the 1.1E+12 vg/mL dose group, four
(>50%) are visual sensitivity responders. These patients also had
improvements in quality of life as measured by a patient reported
outcome survey developed specifically for patients with achromatopsia.
The
two other pediatric patients in the 1.1E+12 vg/mL dose group and three
pediatric patients ages 7 years and younger in the 3E+12vg/mL dose group
(total n=5) could not sufficiently concentrate and consistently
complete the visual sensitivity testing. Similar to other trials where
endpoints are adapted for young children, AGTC plans to work closely
with clinicians and regulators to develop potential adaptations for
younger patients for visual sensitivity testing.
The Company is
currently working on an EOP2 meeting package for the FDA and expects to
receive feedback in the first half of 2022. Subject to these discussions
with FDA, the Company plans to initiate the next phase of AGTC-401
clinical development. The clinical program will be based on the
favorable risk benefit profile of the 1.1E+12 vg/mL dose, which had a
generally safe and well tolerated safety profile across all patients and
signs of biologic response based on improvements in visual sensitivity
and other measures of visual function.
Final data and analysis
of both ACHMA3 and ACHMB3 studies will be presented at relevant
conferences and published for the ophthalmology community.
Conference Call and Webcast
AGTC
will host a conference call and webcast to review the updated and
previously reported interim study results today at 8:00 a.m.ET. To
access the call, dial 877-407-6184 (US) or 201-389-0877 (outside of the
US). A live webcast will be available in the Events and Presentations
section of AGTC’s Investor Relations site at
http://ir.agtc.com/events-and-presentations.
Please log in
approximately 10 minutes prior to the scheduled start time. The archived
webcast will be available in the Events and Presentations section of
the Company's website.
About Achromatopsia (ACHM) Achromatopsia
(ACHM) is an inherited condition caused by mutations in one of several
genes, with the two most common being mutations in either the CNGB3 or
CNGA3 genes. ACHM is associated with extremely poor visual acuity (most
affected individuals are legally blind), extreme light sensitivity
resulting in daytime blindness, and complete loss of color
discrimination. AGTC is currently developing two separate AAV gene
therapy product candidates for the two most prevalent forms of ACHM,
caused by either a genetic mutation in the CNGB3 or CNGA3 genes.
Together, these two genetic mutations account for up to 75% of the ACHM
patient population.
About AGTC AGTC is a
clinical-stage biotechnology company developing genetic therapies for
people with rare and debilitating ophthalmic, otologic and central
nervous system (CNS) diseases. AGTC is a leader in designing and
constructing all critical gene therapy elements and bringing them
together to develop customized therapies with the potential to address
unmet patient needs. AGTC’s most advanced clinical programs leverage its
best-in-class technology platform to potentially improve vision for
patients with inherited retinal diseases. AGTC has active clinical
trials in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM
CNGB3 and ACHM CNGA3). Its preclinical programs build on the company’s
industry leading AAV manufacturing technology and scientific expertise.
AGTC is advancing multiple important pipeline candidates to address
substantial unmet clinical needs in optogenetics, otology and CNS
disorders, and has entered strategic collaborations with companies
including Otonomy, Inc., a biopharmaceutical company dedicated to the
development of innovative therapeutics for neurotology, and Bionic
Sight, LLC, an innovator in the emerging field of optogenetics and
retinal coding. For more information, please visit https://agtc.com/.
Forward-Looking Statements This
release contains forward-looking statements that reflect AGTC's plans,
estimates, assumptions and beliefs, including statements about the
potential of the Company’s late-stage development program in
Achromatopsia (ACHM), including the potential for the clinical
development of AGTC-401 at the second highest dose, the continued
favorable safety profile, the timing of any discussions with the FDA,
and its ability to continue the clinical development of AGTC-401.
Forward-looking statements include all statements that are not
historical facts and can be identified by terms such as "anticipates,"
"believes," "could," "seeks," "estimates," "expects," "intends," "may,"
"plans," "potential," "predicts," "projects," "should," "will," "would"
or similar expressions and the negatives of those terms. Actual results
could differ materially from those discussed in the forward-looking
statements, due to a number of important factors. Risks and
uncertainties that may cause actual results to differ materially
include, among others: gene therapy is still novel with only a few
approved treatments so far; AGTC cannot predict when or if it will
obtain regulatory approval to commercialize a product candidate or
receive reasonable reimbursement; uncertainty inherent in clinical
trials and the regulatory review process; risks and uncertainties
associated with drug development and commercialization; risks and
uncertainties related to funding sources for our development programs;
the direct and indirect impacts of the ongoing COVID-19 pandemic on the
Company’s business, results of operations, and financial condition;
factors that could cause actual results to differ materially from those
described in the forward-looking statements are set forth under the
heading "Risk Factors" in our most recent annual report on Form 10-K and
subsequent periodic reports filed with the SEC. Given these
uncertainties, you should not place undue reliance on these
forward-looking statements. Also, forward-looking statements represent
management's plans, estimates, assumptions and beliefs only as of the
date of this release. Except as required by law, we assume no obligation
to update these forward-looking statements publicly or to update the
reasons actual results could differ materially from those anticipated in
these forward-looking statements, even if new information becomes
available in the future.
BioFlorida is the voice of Florida's life sciences industry, representing 8,600 establishments and research organizations in the BioPharma, MedTech, Digital Health and Health Systems that collectively employ nearly 107,000 Floridians. Source: TEConomy/BIO (released 2022)
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