Not intended for UK Media
- AB-1005 (also known as AAV2-GDNF), an investigational gene
therapy for the treatment of Parkinson’s disease, was well
tolerated with no attributed serious adverse events in all 11
patients at 18 months, meeting the primary objective
- Based on the safety and efficacy results presented, a Phase II
trial (REGENERATE PD) has been developed and is expected to begin
enrolling in the U.S., EU, and UK later this year
Bayer AG and Asklepios BioPharmaceutical, Inc. (AskBio), a gene
therapy company wholly owned and independently operated as a
subsidiary of Bayer AG, on Sunday April 14 presented results from
the 18-month Phase Ib clinical trial for AB-1005, an
investigational gene therapy for treating patients with Parkinson’s
disease (PD).1,2 The data were presented at the American Academy of
Neurology 2024 Annual Meeting in Denver, Colorado, USA.
The study met its primary objective, which was to evaluate the
safety of a one-time bilateral delivery of AB-1005 directly to the
putamen. Eleven patients were enrolled into two cohorts, Mild stage
PD (6 patients) and Moderate stage PD (5 patients), based on timing
from PD clinical diagnosis and the severity of PD symptoms at trial
screening.1
As of November 3, 2023, 57 nonserious adverse events (AEs) and 6
serious adverse events (SAEs) were reported. Most AEs were
transient and were expected perioperative events (<1 month from
treatment). These included headache, tremor, dyskinesia,
arthralgia, musculoskeletal chest pain, fatigue, COVID-19, and
magnetic resonance imaging (MRI) abnormalities. The 6 SAEs reported
in 3 patients (n = 1 in the Mild Cohort and n = 2 in the Moderate
Cohort) were all assessed as unrelated to the treatment by the
Investigator and the Sponsor.
Bilateral infusions of AB-1005 within the putamen (up to 1.8 mL)
were well tolerated, with no SAEs associated with the
investigational gene therapy or contrast agent. Neurosurgical
delivery of AB-1005 resulted in putamen coverage of 63% ± 2%,
exceeding the goal of greater than 50% coverage with AB-1005.
Scheduled 6-month postoperative MRIs revealed findings of
asymptomatic unilateral T1 hypointensity adjacent to 3 of the
putaminal infusion trajectories. Clinical follow-up for up to 5
years post administration is ongoing.2
“These early findings are encouraging and show AB-1005 to be
well tolerated in this study in patients with mild to moderate
Parkinson’s disease,” said Krystof Bankiewicz, MD, PhD, Scientific
Chair, Parkinson’s and MSA, AskBio. “Further, they highlight areas
of potential future exploration in our upcoming Phase II REGENERATE
PD trial, which will look more closely at the potential efficacy of
AB-1005 in the treatment of Parkinson’s disease.”
Patients also completed 18-month neurological assessments and
self-reported questionnaires at regular intervals to evaluate the
severity of motor and non-motor symptoms associated with PD.1
Mild Cohort
The Movement Disorder Society-Unified Parkinson’s Disease Rating
Scale (MDS-UPDRS) is an internationally recognized tool used to
assess the severity of PD symptoms, including motor symptoms. The
Mild Cohort (n = 6) demonstrated relative stability from baseline
to 18 months for both MDS-UPDRS Part II patient-reported Activities
of Daily Living scores and Part III clinician-rated Motor
Examination scores in “ON” and “OFF” medication states.
Patient-reported PD Motor Diaries provide a tool for assessing
patient motor state over an extended 3-day period and then
normalized to a 16-hour waking day. The Mild Cohort (n = 5) showed
a -1.3 hour reduction in “Good ON” time, a 0.2 hour increase in
“ON” time with troublesome dyskinesia, and a 1.1 hour increase in
“OFF” time. One patient in the Mild Cohort declined to complete the
diary after dosing, while troublesome dyskinesia and increased
“OFF” state time in this cohort were driven by another subject with
a genetic defect of unknown pathological significance. These
factors are believed to have contributed to worsening of "Good ON”
state time and “OFF” state time over 18 months for the Mild
Cohort.
Levodopa Equivalent Daily Dose (LEDD) is a summary measure of
all anti-parkinsonian medications taken over a 24-hour period. The
Mild Cohort had a lower LEDD at baseline than the Moderate Cohort
and demonstrated further stability of LEDD over 18
months.
Moderate Cohort
MDS-UPDRS scores for the Moderate Cohort (n = 5) demonstrated a
Part II Activities of Daily Living mean (standard error)
improvement of -3.8 (3.5) points from baseline, and Part III Motor
Examination improvements of –20.4 (4.5) points “OFF” medication,
and –10.6 (3.6) points “ON” medication compared to baseline. Most
PD patients can sense a 3-point reduction of MDS-UPDRS Part III,
and the 20.4-point improvement seen in the “OFF” state in the
Moderate Cohort is considered to represent a large clinical
effect.
Motor Diaries for the Moderate Cohort reported a 2.2-hour
improvement in “Good ON” state time, which was clinically
meaningful; a 0.5-hour reduction in “ON” state with troublesome
dyskinesia; and a 1.7-hour reduction in “OFF” state time. This
equates to a 23.6% ± 11.8% increase in “Good ON” state time and a
33.1% ± 17.4% decrease in “OFF” state time in the Moderate Cohort
at 18 months.
The Moderate Cohort demonstrated a progressive reduction of
dopaminergic medications post-treatment, with a mean 258 ± 162 mg
LEDD reduction from baseline. Notably, the motor improvements
demonstrated were in the setting of a reduced levodopa
requirement.
These outcomes demonstrate that most patients in the Mild Cohort
achieved overall clinical stability with little change in MDS-UPDRS
and PD Motor Diary outcomes and that participants in the Moderate
Cohort achieved clinical motor improvement at 18 months.
AskBio is planning to publish 18-month study results later this
year. Based on the top-line 18-month safety and clinical effects
results presented, a Phase II trial (REGENERATE PD) has been
developed and is expected to begin enrolling patients later this
year in the U.S., EU, and UK.
“We are excited to see AskBio’s investigational gene therapy for
Parkinson’s disease reach significant milestones in clinical
development and look forward to moving into Phase II later this
year,” said Christian Rommel, PhD, Head of Research and Development
at Bayer’s Pharmaceuticals Division. “While much remains to be
done, we recognize with increasing confidence the potential of
AB-1005 to provide a transformative impact for patients in the
future.”
About AB-1005
AB-1005 is an investigational gene therapy based on
adeno-associated viral vector serotype 2 (AAV2) containing the
human glial cell line-derived neurotrophic factor (GDNF) transgene,
which allows for stable and continuous expression of GDNF in
localized regions of the brain after direct neurosurgical injection
with magnetic resonance imaging (MRI)-monitored convection enhanced
delivery.3,4 GDNF is a homodimer that is a distantly related member
of the transforming growth factor-β superfamily. In midbrain
neuronal cell cultures, recombinant human GDNF promoted the
survival and morphological differentiation of dopaminergic neurons
and increased their high-affinity dopamine uptake. GDNF has long
been evaluated as a potential treatment for diseases, such as
Parkinson’s, marked by progressive degeneration of midbrain
dopaminergic neurons.5
About the AB-1005 Phase Ib trial
In this Phase Ib, multi-center, multi-site, parallel assignment,
non-randomized trial, 11 patients were administered AB-1005 to the
putamen via one-time bilateral convection-enhanced delivery.
Patients were enrolled into two cohorts, Mild (6 patients) and
Moderate (5 patients), based upon the duration and stage of their
PD. The objective of this investigation was to evaluate the safety
and potential clinical effect of AB-1005 delivered to the putamen
in patients with either a recent or a long-standing diagnosis of
PD. The outcomes assessed at 18 months were incidence of
Treatment-Emergent Adverse Events (TEAEs) as reported by the
patients or assessed clinically by physical and neurological
examinations, motor symptoms as reported via the Movement Disorder
Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and
PD Motor Diary self-assessments, and non-motor symptoms of PD and
brain dopaminergic network integrity as measured by DaTSCAN.1 These
assessments will continue for up to five years. For more
information, visit clinicaltrials.gov (NCT#04167540), visit
askbio.com, or send an email to AskFirst@askbio.com.
About Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative disorder
caused by the death of nerve cells in the brain, leading to
decreased dopamine levels.6 At diagnosis, it is estimated that
patients have already lost 50-80% of their dopaminergic neurons.7
The loss of these neurons leads to a progressive loss of motor
function and symptoms such as tremors, muscle rigidity, and
slowness of movement.8 Even with medication, the symptoms of
Parkinson’s disease can fluctuate during the course of the day.
According to the Parkinson’s Foundation, more than 10 million
people worldwide suffer from Parkinson’s disease9, with
approximately one million living in the United States.9 There is no
cure, and the effectiveness of current treatments frequently
decreases over time.10
About AskBio
Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and
independently operated subsidiary of Bayer AG, is a fully
integrated gene therapy company dedicated to developing life-saving
medicines and changing lives. The company maintains a portfolio of
clinical programs across a range of neuromuscular, central nervous
system, cardiovascular and metabolic disease indications with a
clinical-stage pipeline that includes therapeutics for congestive
heart failure, Huntington’s disease, limb-girdle muscular
dystrophy, multiple system atrophy, Parkinson’s disease, and Pompe
disease. AskBio’s gene therapy platform includes Pro10™, an
industry-leading proprietary cell line manufacturing process, and
an extensive capsid and promoter library. With global headquarters
in Research Triangle Park, North Carolina, and European
headquarters in Edinburgh, Scotland, the company has generated
hundreds of proprietary capsids and promoters, several of which
have entered pre-clinical and clinical testing. An early innovator
in the gene therapy field, with over 900 employees in five
countries, the company holds more than 800 patents and patent
applications in areas such as AAV production and chimeric capsids.
Learn more at www.askbio.com or follow us on LinkedIn.
About Bayer
Bayer is a global enterprise with core competencies in the life
science fields of health care and nutrition. In line with its
mission, “Health for all, Hunger for none,” the company’s products
and services are designed to help people and the planet thrive by
supporting efforts to master the major challenges presented by a
growing and aging global population. Bayer is committed to driving
sustainable development and generating a positive impact with its
businesses. At the same time, the Group aims to increase its
earning power and create value through innovation and growth. The
Bayer brand stands for trust, reliability and quality throughout
the world. In fiscal 2023, the Group employed around 100,000 people
and had sales of 47.6 billion euros. R&D expenses before
special items amounted to 5.8 billion euros. For more information,
go to www.bayer.com
Find more information about AskBio at www.askbio.comFind more
information about Bayer at https://pharma.bayer.com/Follow Bayer on
Facebook: http://www.facebook.com/bayerFollow Bayer on Twitter:
@BayerPharma
naf
(2024-0060e)
Bayer Forward-Looking Statements
This release may contain forward-looking statements based on
current assumptions and forecasts made by Bayer management. Various
known and unknown risks, uncertainties and other factors could lead
to material differences between the actual future results,
financial situation, development or performance of the company and
the estimates given here. These factors include those discussed in
Bayer’s public reports which are available on the Bayer website at
www.bayer.com. The company assumes no liability whatsoever to
update these forward-looking statements or to conform them to
future events or developments.
AskBio Forward-Looking Statements
This press release contains “forward-looking statements.” Any
statements contained in this press release that are not statements
of historical fact may be deemed to be forward-looking statements.
Words such as “believes,” “anticipates,” “plans,” “expects,”
“will,” “intends,” “potential,” “possible” and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements include without limitation statements
regarding AskBio’s clinical trials. These forward-looking
statements involve risks and uncertainties, many of which are
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may not be able to execute on its business plans and goals,
including meeting its expected or planned clinical and regulatory
milestones and timelines, its reliance on third-parties, clinical
development plans, manufacturing processes and plans, and bringing
its product candidates to market, due to a variety of reasons,
including possible limitations of company financial and other
resources, manufacturing limitations that may not be anticipated or
resolved in a timely manner, potential disagreements or other
issues with our third-party collaborators and partners, and
regulatory, court or agency feedback or decisions, such as feedback
and decisions from the United States Food and Drug Administration
or the United States Patent and Trademark Office. Any of the
foregoing risks could materially and adversely affect AskBio’s
business and results of operations. You should not place undue
reliance on the forward-looking statements contained in this press
release. AskBio does not undertake any obligation to publicly
update its forward-looking statements based on events or
circumstances after the date hereof.
###
[1] GDNF Gene Therapy for Parkinson’s Disease. Available at:
https://classic.clinicaltrials.gov/ct2/show/NCT04167540. Accessed
April 2024.
[2] Asklepios BioPharmaceutical. Data on file.
[3] Heiss JD, Lungu C, Hammoud DA, Herscovitch P, Ehrlich DJ,
Argersinger DP, Sinharay S, Scott G, Wu T, Federoff HJ, Zaghloul
KA, Hallett M, Lonser RR, Bankiewicz KS. Trial of magnetic
resonance-guided putaminal gene therapy for advanced Parkinson’s
disease. Mov Disord. 2019 Jul;34(7):1073-1078.
[4] Kells AP, Eberling J, Su X, Pivirotto P, Bringas J, Hadaczek
P, Narrow WC, Bowers WJ, Federoff HJ, Forsayeth J, Bankiewicz KS.
Regeneration of the MPTP-lesioned dopaminergic system after
convection-enhanced delivery of AAV2-GDNF. J Neurosci. 2010 Jul
14;30(28):9567-77.
[5] Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a
glial cell line-derived neurotrophic factor for midbrain
dopaminergic neurons. Science. 1993;260(5111):1130-1132.
[6] Michael J. Fox Foundation. Parkinson’s 101 - What is
Parkinson’s disease? Available at:
https://www.michaeljfox.org/parkinsons-101. Accessed: April
2024.
[7] DeMaagd G, Philip A. Parkinson's Disease and Its Management:
Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical
Presentation, and Diagnosis. P T. 2015 Aug;40(8):504-32. PMID:
26236139; PMCID: PMC4517533.
[8] Parkinson’s Foundation. Motor-fluctuations. Available at:
https://www.parkinson.org/library/fact-sheets/motor-fluctuations.
Accessed: April 2024.
[9] Parkinson’s Foundation. Who has Parkinson’s? Available at:
https://www.parkinson.org/understanding-parkinsons/statistics.
Accessed: April 2024.
[10] Mayo Clinic. Parkinson’s disease. Available at:
https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/diagnosis-treatment/drc-20376062.
Accessed: April 2024.
Phil McNamara
AskBio Media Contact
+1 (984) 5207211
pmcnamara@askbio.com
Dr. Nuria Aiguabella Font
Bayer Global Media Contact
+49 (173) 2329691
nuria.aiguabellafont@bayer.com
Carolyn Nagle
Bayer U.S. Media Contact
+1 (201) 4190337
carolyn.nagle@bayer.com
Contact for investor inquiries
Bayer Investor Relations Team
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ir@bayer.com