Voyager continues to plan to submit a BLA for
VY-AADC based on its pivotal program and Type C meeting
feedback
Voyager Therapeutics, Inc. (NASDAQ:VYGR), a clinical-stage gene
therapy company focused on developing life-changing treatments for
severe neurological diseases today announced feedback from a Type C
meeting with the U.S. Food and Drug Administration (FDA).
Based on the written response from the FDA, Voyager continues
to plan to submit for review a biologics license application (BLA)
for VY-AADC based on the nonclinical and clinical safety and
efficacy data from the pivotal program, including plans to submit a
BLA based on data from the randomized, placebo-controlled Phase 2
trial alone, or if needed, from the randomized, placebo-controlled
Phase 3 trial.
In addition, Voyager today announced positive
interim results from a Phase 1 posterior trajectory trial that
achieved enhanced coverage of the putamen, reduced surgical times,
and improvements in patients’ motor function at six months that
were consistent with improvements achieved from patients in Cohorts
2 and 3 at the same time point in Voyager’s Phase 1b trial with
VY-AADC. As a result, Voyager has determined that the posterior
approach will continue to serve as the preferred surgical route of
administration and that the pivotal program will use a dose
concentration of VY-AADC between those used in Cohorts 2 and 3 from
the Phase 1b trial.
“We are very pleased with feedback from the FDA
regarding our pivotal program for VY-AADC that includes the
potential to file a BLA based on the safety and efficacy results
from the Phase 2 trial, or if needed, from the Phase 3 trial,” said
Robert Pietrusko, Pharm.D., senior vice president of regulatory
affairs and quality assurance at Voyager. “With the recent RMAT
designation for VY-AADC and written feedback from the FDA regarding
our Type C meeting questions, we look forward to continuing to work
closely with the agency to expedite the development of this
potentially important treatment for patients with Parkinson’s
disease.”
“Our VY-AADC program is progressing nicely and
our plans are now further informed by this Type C regulatory
feedback,” said Andre Turenne, president and chief executive
officer of Voyager. “We appreciate the agency’s guidance and look
forward to incorporating their feedback as we advance into our
pivotal program. Importantly, the data from the posterior
trajectory trial supports the results from Cohorts 2 and 3 from the
Phase 1b trial and informs our selection of a dose concentration
and route of delivery for our pivotal program.”
Highlights from Type C meeting feedback
from FDA
Voyager recently submitted questions to the FDA
in preparation for a planned Type C meeting to discuss the
regulatory pathway for VY-AADC for the treatment of Parkinson’s
disease in patients with motor fluctuations that are refractory to
medical management. The purpose of the Type C meeting was to
request feedback on the design of Voyager’s planned pivotal program
for VY-AADC that includes a Phase 2 and Phase 3 trial conducted in
staggered parallel initiation and the potential to submit for
review a BLA based on the nonclinical results and clinical results
from this planned pivotal program.
The FDA indicated in a written response to
Voyager that the Phase 2 randomized, placebo-controlled trial in
approximately 42 patients, if it were to meet its primary endpoint
of demonstrating a statistically-significant difference of diary
on-time without troublesome dyskinesia compared to the placebo
surgery group and in the absence of major safety concerns, likely
may be considered sufficient for acceptance of submission for
review of a BLA. The agency also indicated that if the results of
the Phase 2 trial were supportive only and did not achieve the
primary endpoint, the randomized, placebo-controlled Phase 3 trial
in approximately 120 patients, if it were to achieve the primary
endpoint and in the absence of major safety concerns, also likely
may be considered sufficient for acceptance of submission for
review of a BLA. Voyager also submitted questions to the agency
regarding chemistry, manufacturing and controls (CMC) and
nonclinical information for VY-AADC. Voyager believes that the
written responses from the agency to these questions were
informative and can be addressed to support the submission of a BLA
for review.
Preliminary data from the Phase 1
posterior trajectory trial and data from the prior Phase 1b trial
with VY-AADC supports the surgical approach and dose selection for
the pivotal program for Parkinson’s disease
Investigators successfully dosed eight patients
with VY-AADC in a Phase 1 trial in patients with Parkinson’s
disease exploring the posterior (i.e., back of the head) infusion
trajectory of VY-AADC and using the same dose concentration to
patients in Cohort 3 from the Phase 1b trial. The posterior
trajectory better aligns the infusion of VY-AADC with the
anatomical structure of the putamen. As previously reported from
all eight patients, this trajectory resulted in a greater average
coverage of the putamen (approximately 50%) and reduced the total
procedure time by two to three hours compared to Cohorts 1, 2 and 3
from the Phase 1b trial that employed a transfrontal, or top of the
head, delivery approach into the putamen. In all eight patients,
treatment with VY-AADC has been well-tolerated and no serious
adverse events have been reported to date.
Today’s update includes interim biomarker and
motor function data from four of eight patients who have completed
their motor function assessments at six months. On average, patient
characteristics at baseline in this trial were consistent with
patients in the Phase 1b trial, namely, patients on average were 57
years of age with a Parkinson’s disease diagnosis for an average of
nine years and all were candidates for surgical intervention
including deep-brain stimulation due to disabling motor
complications despite treatment with optimal anti-Parkinsonian
medication.
From baseline to six months, treatment with
VY-AADC increased AADC enzyme activity in the putamen as measured
by positron emission tomography (PET) using [18F] fluorodopa (or
18F-DOPA), which reflects the capacity of neurons in the brain to
convert levodopa to dopamine. The increase in AADC enzyme
activity in this trial was consistent with increases in AADC enzyme
activity observed from patients in Cohort 3 from the Phase 1b
trial.
Treatment with VY-AADC improved patients’ motor
function from baseline to six months across multiple assessments in
a clinically-meaningful manner and consistent with results from
Cohorts 2 and 3 from the Phase 1b trial during the same period of
time. These assessments include patient self-reported diaries, both
on- and off-times and diary on-time without troublesome dyskinesia,
Unified Parkinson’s Disease Rating Scales, and activities of daily
living measures. In addition, improvements in patients’ motor
function using the posterior trajectory approach were observed with
significant reductions in patients’ oral levodopa and equivalent
medications, similar to results observed from Cohorts 2 and 3 from
the Phase 1b trial. Voyager plans to present data from the full
cohort of eight patients from the Phase 1 posterior trajectory
trial at future scientific and medical conferences.
Based on the safety, coverage of the putamen,
PET imaging data, and reduced surgical times from the eight
patients treated in this trial, the posterior approach will serve
as the preferred infusion trajectory for the Phase 2 and 3 trials.
In addition, based on results from the 15 patients treated in
Cohorts 1, 2 and 3 from the Phase 1b trial and the eight patients
dosed in the Phase 1 posterior trajectory trial including the four
of eight patients who have completed their motor function
assessments at six months, Voyager has chosen a dose concentration
of VY-AADC for the pivotal program that is between the dose
concentrations of Cohorts 2 and 3 from the Phase 1b trial.
Twenty-four clinical trial sites (including
neurosurgical and neurology patient referral sites) have been
selected for participation in the Phase 2 trial with institutional
review board submission and site activation underway. During the
remainder of the year, Voyager plans to provide updates as to the
enrollment status of this trial.
For more information about Voyager’s Phase 2
clinical trial with its gene therapy program VY-AADC for the
treatment of Parkinson’s disease, please use the following
link:https://clinicaltrials.gov/ct2/results?cond=&term=+NCT03562494&cntry=&state=&city=&dist
For additional information regarding this Phase
2 clinical trial, please email Voyager at:
clinicaltrials@vygr.com.
About Parkinson’s Disease and
VY-AADC
Parkinson’s disease is a chronic, progressive
and debilitating neurodegenerative disease that affects
approximately 1,000,000 people in the U.S.1 and seven to 10 million
people worldwide2. While the underlying cause of Parkinson’s
disease in most patients is unknown, the motor symptoms of the
disease arise from a loss of neurons in the midbrain that produce
the neurotransmitter dopamine. Declining levels of dopamine in this
region of the brain, the putamen, leads to the motor symptoms
associated with Parkinson’s disease including tremors, slow
movement or loss of movement, rigidity, and postural
instability. Motor symptoms during the advanced stages of the
disease include falling, gait freezing, and difficulty with speech
and swallowing, with patients often requiring the daily assistance
of a caregiver.
There are currently no therapies that
effectively slow or reverse the progression of Parkinson’s disease.
Levodopa remains the standard of care treatment, with its
beneficial effects on symptom control having been discovered over
40 years ago3. Patients are generally well-controlled with oral
levodopa in the early stages of the disease but become less
responsive to treatment as the disease progresses. Patients
experience longer periods of reduced mobility and stiffness termed
off-time, or the time when medication is no longer providing
benefit, and shorter periods of on-time when their medication is
effective.
The progressive motor symptoms of Parkinson’s
disease are largely due to the death of dopamine neurons in the
substantia nigra, a part of the midbrain that converts levodopa to
dopamine, in a single step catalyzed by the enzyme AADC.
Neurons in the substantia nigra release dopamine into the putamen
where the receptors for dopamine reside. In Parkinson’s
disease, neurons in the substantia nigra degenerate and the enzyme
AADC is markedly reduced in the putamen, which limits the brain’s
ability to convert oral levodopa to dopamine4. The intrinsic
neurons in the putamen, however, do not degenerate in Parkinson’s
disease5,6. VY-AADC, comprised of the adeno-associated virus-2
capsid and a cytomegalovirus promoter to drive AADC transgene
expression, is designed to deliver the AADC gene directly into
neurons of the putamen where dopamine receptors are located,
bypassing the substantia nigra neurons and enabling the neurons of
the putamen to express the AADC enzyme to convert levodopa into
dopamine. The approach with VY-AADC, therefore, has the
potential to durably enhance the conversion of levodopa to dopamine
and provide clinically meaningful improvements by restoring motor
function in patients and improving symptoms following a single
administration.
The FDA granted Regenerative Medicine Advanced
Therapy (RMAT) designation for VY-AADC for the treatment of
Parkinson’s disease in patients with motor fluctuations that are
refractory to medical management. RMAT designation is an expedited
program for the advancement and approval of regenerative medicine
products, including gene therapy products. RMAT designation was
granted based on clinical data from the Phase 1b trial with VY-AADC
in patients with Parkinson’s disease. During this trial, one-time
administrations of VY-AADC demonstrated robust and durable
improvements in patients’ motor function along with substantial
reductions in use of daily oral levodopa and other Parkinson’s
disease medications. Infusions of VY-AADC have been well-tolerated
in this trial with no vector-related serious adverse events
reported to date.
About Voyager Therapeutics
Voyager Therapeutics is a clinical-stage gene
therapy company focused on developing life-changing treatments for
severe neurological diseases. Voyager is committed to advancing the
field of AAV gene therapy through innovation and investment in
vector engineering and optimization, manufacturing and dosing and
delivery techniques. Voyager’s pipeline focuses on severe
neurological diseases in need of effective new therapies, including
Parkinson’s disease, a monogenic form of ALS called SOD1,
Huntington’s disease, Friedreich’s ataxia, neurodegenerative
diseases related to defective or excess aggregation of tau protein
in the brain including Alzheimer’s disease and severe, chronic
pain. Voyager has broad strategic collaborations with Sanofi
Genzyme, the specialty care global business unit of Sanofi, AbbVie,
and the University of Massachusetts Medical School. Founded
by scientific and clinical leaders in the fields of AAV gene
therapy, expressed RNA interference and neuroscience, Voyager
Therapeutics is headquartered in Cambridge, Massachusetts. For more
information, please visit www.voyagertherapeutics.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 “may,” “might,” “will,”
“would,” “should,” “expect,” “plan,” “anticipate,” “believe,”
“estimate,” “undoubtedly,” “project,” “intend,” “future,”
“potential,” or “continue,” and other similar expressions are
intended to identify forward-looking statements. For example, all
statements Voyager makes regarding the initiation, timing, progress
and reporting of results of its preclinical programs and clinical
trials and its research and development programs, its ability to
advance its AAV-based gene therapies into, and successfully
initiate, enroll and complete, clinical trials, the potential
clinical utility of its product candidates, its ability to continue
to develop its gene therapy platform, its ability to develop
manufacturing capability for its products and successfully
transition its manufacturing process, its ability to perform under
existing collaborations with, among others, Sanofi Genzyme and
AbbVie and to add new programs to its pipeline, its ability to
enter into new partnerships or collaborations, and the timing or
likelihood of its regulatory filings and approvals, are forward
looking. All forward-looking statements are based on estimates and
assumptions by Voyager’s management that, although Voyager 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 Voyager
expected. Such risks and uncertainties include, among others,
the initiation and conduct of preclinical studies and clinical
trials; the availability of data from clinical trials; the
expectations for regulatory submissions and approvals; the
continued development of the gene therapy platform; Voyager’s
scientific approach and general development progress; and the
availability or commercial potential of Voyager’s product
candidates. These statements are also subject to a number of
material risks and uncertainties that are described in Voyager’s
most recent Annual Report on Form 10-K filed with the Securities
and Exchange Commission, 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.
Voyager undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events or otherwise, except as required by law.
___________________________
1 Willis et al, Neuroepidemiology.2010;34:143–151
2 www.pdf.org/en/parkinson_statistics
3 Poewe W, et al, Clinical Interventions in
Aging.2010;5:229-238.
4 Lloyd, J Pharmacol Exp Ther. 1975;195:453-464, Nagatsu, J
Neural Transm Suppl.2007
5 Cold Spring Harb Perspect Med 2012;2:a009258
6 Braak et al, Cell Tissue Res.2004;318:121-134
Investor Relations:
Matt Osborne
Vice President of Investor Relations & Corporate Communications
857-259-5353
mosborne@vygr.com
Media:
Julie Normart
W2O Group
+1 (415) 946-1087
jnormart@w2ogroup.com
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