- World’s First
Therapeutic Agent for Regenerating Brain -
SanBio Co., Ltd. (TOKYO:4592) (head office: Tokyo,
representative director & CEO: Keita Mori) hereby announces
that today on July 31 2024, it obtained conditional and
time-limited marketing approval for the human somatic stem
cell-processed product “AKUUGO® suspension for intracranial
implantation” (INN: vandefitemcel; hereafter, “AKUUGO®”) in Japan,
for the indication of improving chronic motor paralysis resulting
from traumatic brain injury.
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Vial containing cell suspension for
intracranial implantation (Photo: Business Wire)
Traumatic brain injury (TBI) is caused by a strong external
force, such as from a traffic accident or a fall, applied to the
head, damaging the brain tissue within the skull. The manifestation
and timing of symptoms of TBI vary widely among patients, and
depending on the affected area of the brain, patients may
experience aftereffects such as motor dysfunction or higher brain
dysfunction. Studies suggest that destroyed or damaged brain
tissues do not regenerate naturally, and patients who enter the
chronic phase of TBI and develop motor paralysis face lifelong
impacts on their daily and social lives, indicating that there is a
significant unmet medical need.
AKUUGO® has been shown to be effective in improving chronic
motor paralysis associated with TBI, and is the world’s first and
only allogeneic cell therapeutic agent* approved for this
indication. AKUUGO® is also a world first in that it facilitates
the regeneration of brain, and its approval for practical clinical
use marks a significant milestone. AKUUGO® is an allogeneic cell
product manufactured by culturing bone marrow-derived mesenchymal
stem cells collected from healthy donors and transiently
transfecting the human Notch-1 intracellular domain gene into the
cultured cells to enhance their ability to regenerate nerve cells.
The transplantation of AKUUGO® into damaged nerve tissues in the
brain is expected to trigger the release of FGF-2 (a type of
protein) and other substances, which in turn will promote the
natural regenerative ability of damaged nerve cells and induce
proliferation and differentiation of nerve cells. The results of
basic research have also shown that AKUUGO® has protective effects
on nerve cells, induces angiogenesis, and demonstrates
immunomodulating effects.
Mori Keita CEO of SanBio commented as follows.
“We are extremely pleased to announce that we have obtained
conditional and time-limited approval for AKUUGO® after 24 years in
operation, enabling us to provide it as a new treatment option for
TBI patients in Japan. AKUUGO®, which is directly administered to
the brain, represents an innovative and crucial choice for patients
with chronic motor paralysis associated with TBI. Through AKUUGO®,
we hope to bring hope to the lives of as many TBI patients as
possible.”
The approval of AKUUGO® was based on the results of the global
Phase 2 clinical trial SanBio conducted in Japan and the United
States. Dr. Nobuhito Saito, Professor of Neurology at the
University of Tokyo led the clinical trial, commented as
follows.
“Traumatic brain injury can affect various areas of the brain,
and the site and extent of the damage determine the duration and
severity of symptoms, as well as aftereffects. Rehabilitation in
the acute phase is effective in restoring a certain level of motor
function; however, because damaged brain cells do not regenerate,
there has been no effective treatment for chronic motor deficit and
other aftereffects of traumatic brain injury. The approval of
AKUUGO® may provide a new treatment option for patients suffering
from the chronic aftereffects of traumatic brain injury, and I look
forward to seeing further progress in research and analysis.”
Dr. David O. Okonkwo, Professor of neurological surgery and
director of the Neurotrauma Clinical Trials Center at University of
Pittsburg commented as follows.
“Patients with chronic traumatic brain injury experience
lifelong disability affecting quality of life, particularly those
with motor deficits. Living with traumatic brain injury also places
burdens on the caregivers who support them. The approval of AKUUGO®
is a breakthrough and opens a new chapter in the treatment of motor
deficits in chronic traumatic brain injury.”
Dr. Hideyuki Okano, a Keio University professor and SanBio’s
founding scientist who has supported the Company over many years,
commented as follows.
“For more than 20 years, SanBio has conducted R&D in the
field of brain regenerative medicine. I’m pleased that AKUUGO® has
been approved for treating chronic motor paralysis resulting from
traumatic brain injury, the first such treatment to be approved in
the world, and thrilled to offer the product as a new treatment
option to patients in Japan. The approval of AKUUGO® in Japan,
ahead of anywhere else in the world, brings us closer to achieving
our goal of supporting patients with central nervous system
disorders, especially brain disorders, around the world who still
suffer from the lack of effective treatment options.“
Reference
Product Overview
Brand name
AKUUGO® Suspension for Intracranial
Implantation
Generic name
Vandefitemcel
Indications and effects
Improvement of chronic motor paralysis
associated with traumatic brain injury
Dosage and administration
For adults, implant 5 x106 live human
(allogeneic) bone marrow-derived mesenchymal stem cells (300μL of
cell suspension) to perilesional brain tissues via stereotactic
brain surgery using the dedicated delivery device set.
Implant the cells into the perilesional
area through three trajectories via a burr hole made in the skull.
To each trajectory, inject 100μL of the cell suspension, depositing
20μL of the solution each across a total of five sites placed at
5–6mm intervals from the deepest site. The rate of implantation
should be approximately 10μL/min. Follow the steps below for
implantation.
1. Before starting the procedure, attach
the guide & stop and stylet-equipped inserter from the
dedicated delivery device set to the head fixation device for
invasive neurosurgery.
2. Thaw the cell suspension for
intracranial implantation, wash it with the dedicated preparation
solution, and adjust the concentration of the cell suspension to
1.67 x 106 cells/100μL using the dedicated preparation solution.
Cleanse the micro-syringe fixed with the cannula from the dedicated
delivery device set with the dedicated preparation solution before
filling it with the prepared cell suspension.
Date of marketing approval
July 31, 2024
Condition of approval 1. Considering the limited
manufacturing record for the Product, the Company shall promptly
collect information on the Product’s quality based on a
pre-determined plan, and evaluate and report on the
equivalence/homogeneity, in terms of quality, of the
investigational product (clinical trials product) and the Product
intended for commercial distribution. Based on the evaluation
results, the Company shall apply for a partial change of approved
matters. It shall not ship the Product until the partial change
application has been approved.
2.
The Company must ensure that the Product is used in medical
facilities fully equipped to handle emergencies, by physicians who
possess sufficient knowledge and experience in the diagnosis and
treatment of traumatic brain injury and stereotactic brain surgery
techniques. The physicians must also have sufficient knowledge of
the clinical trial results and adverse events of the Product.
3.
Until the Company re-applies for marketing approval for the Product
prior to the expiration of the conditional and time-limited
approval, the Company must conduct post-marketing evaluation of all
cases where the Product is used.
4.
Until the Company re-applies for marketing
approval for the Product prior to the expiration of the conditional
and time-limited approval, the Company must collect information on
the biological characteristics reflecting the mechanisms of action
of the Product and take necessary measures, such as improving its
quality control strategy.
*About allogeneic cell transplantation Regenerative
medicine therapies can be classified into autologous and allogeneic
cell therapies. In autologous cell transplantation, the patient’s
own cells are harvested and used, but cell processing procedures
are time-consuming and labor-intensive. In allogeneic cell
transplantation, on the other hand, cells are collected from a
donor and cultured in large quantities. Since allogeneic cell
medicines can be mass produced, they can treat a large number of
patients.
About Traumatic Brain Injury Traumatic brain injury (TBI)
is one of the leading causes of death and disability worldwide. The
estimated global incidence of acute TBI during 2016 was 27 million
cases, and the estimated global prevalence of chronic impairment
secondary to TBI was 55.5 million cases*1. Overall, TBI and
long-term motor deficits secondary to TBI significantly impair a
person’s self-care, employability, and quality of life, and are
major burdens on healthcare systems worldwide. In the United
States, approximately 43% of surviving hospitalized persons with
TBI experience long-term disabilities*2, and it is estimated that
3.17 million people are living with long-term disabilities
secondary to TBI*3. There are about 60,000*4 TBI patients in Japan,
and of which, 20%*5 are estimated to suffer from aftereffects of
the injury.
About "AKUUGO® suspension for intracranial
implantation” AKUUGO® suspension for intracranial
implantation(INN: vandefitemcel) is a human (allogeneic) bone
marrow-derived modified mesenchymal stem cell that is produced by
modifying and culturing mesenchymal stem cells derived from the
bone marrow aspirate of healthy adults. The transplantation of
AKUUGO® into damaged nerve tissues in the brain is expected to
trigger the release of FGF-2 (a type of protein) and other
substances, which in turn will promote the natural regenerative
ability of damaged nerve cells and induce proliferation and
differentiation of nerve cells. The conditional and time-limited
approval was based on the results of SanBio’s global Phase 2
clinical trial. The primary endpoint of the trial—mean change from
baseline in Fugle-Meyer Motor Scale (FMMS) score at 24 weeks after
treatment—was met, with the AKUUGO®-treated group reporting
8.3-point improvement versus 2.3 for the control group,
demonstrating a statistically significant difference. The final
analysis of the study was presented at the annual meeting of
American Academy of Neurology. We are pushing forward with R&D
targeting multiple indications, including chronic effects
associated with chronic cerebral infarction.
About SanBio Group (SanBio Co., Ltd. and SanBio, Inc.)
SanBio is engaged in the regenerative cell business—we research,
develop, manufacture, and sell regenerative cell medicines. In July
2024, under the Sakigake Designation Program, we obtained
conditional and time-limited approval for our mainstay product
AKUUGO® for the indication of improving chronic motor deficit
resulting from traumatic brain injury. Going forward, we will
continue focusing our R&D efforts on central nervous system
disorders with significant unmet medical needs that cannot be
addressed by existing medicine or drugs. The Company is
headquartered in Tokyo, Japan and Oakland, California, and
additional information about SanBio Group is available at
https://sanbio.com/en/
References
1 James SL, et al. “Global, regional, and national burden of
traumatic brain injury and spinal cord injury, 1990- 2016: a
systematic analysis for the Global Burden of Disease Study 2016.”
Lancet Neurol 2019;18:56-87.
2 Selassie AW, et al. “Incidence of long-term disability
following traumatic brain injury hospitalization, U.S.”, 2003. J
Head Trauma Rehabil 2008;23:123-31
3 Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of
long-term disability from traumatic brain injury in the civilian
population of the United States, 2005. J Head Trauma Rehabil. 2008
Nov-Dec;23(6):394-400.
4 The number of patients under “19 Injury, poisoning, and other
consequences of external causes (intracranial injuries)” in Patient
Survey 2020, the Ministry of Health, Labour and Welfare
5 The number of patients under “T905 After effects of
intracranial injury” in Patient Survey 2020, the Ministry of
Health, Labour and Welfare
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For more information, contact: SanBio Co., Ltd.
Management Administration Email: info@sanbio.com