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February 26, 2004
Investigational
New Drug (IND) application filedwith the USFDA for
HGF genetic medicine against ischemic heart disease
-Peripheral arterial disease and ischemic
heart disease related clinical trials in the USA- |
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AnGes MG filed an investigational new drug (IND)
application for hepatocyte growth factor (HGF) genetic medicine
with the Food and Drug Administration (FDA) on February 25,
2004 through its US subsidiary, AnGes Inc. in order to start
Phase I study of medicine against ischemic heart disease (IHD).
In the USA, AnGes MG has been conducting Phase II clinical trials
for HGF genetic medicine against peripheral arterial disease
(PAD) since April 2003. In addition, AnGes MG intends to start
conducting IHD related clinical trials in the near future, as
a larger number of patients are affected, thereby aiming to
launch HGF genetic medicine for both diseases at an early date.
HGF genetic medicine has a neovascular effect and is intended
to cure ischemic disease in which the lumenblood vessels narrows
due to arteriosclerosis and the blood flow is impaired. As this
medicine's effect differ from that of other conventional drugs,
it is expected to be effective for patients who do not sufficiently
respond to conventional drug therapy or who cannot undergo surgery.
AnGes MG has been developing this medicine in fields centering
around PAD, where the blood circulation in the lower limbs is
decreases (obstructive arteriosclerosis and Buerger's disease),
and IHD, in which the blood flow in the heart is impaired.
The objective of the current IND application is to start the
Phase I clinical trial of HGF genetic medicine in the field
of ischemic heart disease in the USA. Generally, the Phase I
clinical trials are conducted to verify safety and healthy volunteers
are used as subjects. However, in this development project of
HGF genetic medicine for ischemic heart disease, AnGes MG is
going to administer the medicine to a limited number of patients
with severe ischemic heart disease using a catheter for direct
administration of the medicine to the ischemic lesions, beginning
with the Phase I trial. This is for the purpose of verifying
the safety as well as the efficacy of the medicine. Since the
IND application for starting the Phase I clinical trial for
IHD in the USA, AnGes MG has been preparing for the start of
clinical trials related to the same diseases in Japan during
2004.
In addition to the PAD related Phase II clinical study of HGF
genetic medicine now underway in the USA, AnGes MG is going
to begin PAD related multi-center double blind Phase III clinical
trials soon in Japan. With the IND application for HGF medicine
to treat IHD, AnGes MG aims to concurrently develop this medicine
for use against both PAD and IHD in Japan and the USA.
AnGes MG has granted Daiichi Pharmaceutical Co., Ltd. the distribution
rights for HGF genetic medicine in both the PAD and IHD fields
in Japan, the US and Europe. |
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 Specific
therapeutic significance of the HGF genetic medicine
It is known that HGF has a strong vascularization effect; the
present pharmaceutical agent deposits a gene to produce HGF
in sites of vascular necrosis, thus the HGF protein is generated
locally, resulting in blood vessel regeneration to improve the
(arteriosclerotic) condition - the first genetic medication
to be produced in Japan. The agent thus developed does not employ
a virus vector to introduce the genetic sequence to a patient's
DNA - it is a pure, "naked" DNA sequence, so negative
effects that usually accompany a DNA sequence introduction with
a virus vector do not appear here. In addition, since the present
medicine alters the condition of necrosis by regenerating the
blood vessels, as opposed to all conventional pharmaceutical
agents, positive results can be expected in cases when conventional
therapy for PAD and IHD fails, or is increasingly complicated.
Explanation
of specialized terms
1. Gene medicine
A medicine, wholly, or partially comprising a genetic expression.
2. Hepatocyte Growth Factor (HGF)
A growth factor developed from hepatocytes; in addition to blood
vessel regeneration, it initiates various processes necessary
for tissue / organ regeneration during organ formation (organogenesis).
3. Peripheral arterial disease (PAD)
Since peripheral blood vessels of the four limbs can become
clogged, so that the supply of blood to muscle and skin tissues
is not adversely affected, causing the following symptoms: a
feeling of paralysis, coldness, arrest of blood flow (intermittent
claudication), ulcer of lower limbs (thrombic disease), pain
even when there is no motion. A condition characteristic of
arteriosclerosis obliterans (ASO), Buerger's disease. There
are approximately 100,000 patients in Japan and 1,000,000 -
in the U.S.A.
4. Ischemic heart disease (IHD)
Vessels supplying the heart (coronary blood vessels) become
contracted (or constricted) to a certain extent resulting in
insufficient blood flow after physical activity; characteristic
symptoms are angina pectoris accompanied with a tightness in
the chest and chest pains, and myocardial infarction causes
by disorders of coronary blood vessels becoming completely clogged
- heart muscle tissue becoming ischemic. There are approximately
100,000 patients in Japan who underwent angioplasty surgery
due to severe heart disease, and 1.8 million - in the U.S.
5. Naked DNA
For a genetic expression to work properly, genes have
to enter a cell; in conventional practice, however, genes may
only come as close as to be attached to the cell membrane, unable
to penetrate it. A carrier, an agent to introduce the genetic
expression to a cell, becomes necessary at this point. An improved
virus vector (i.e., purified not to pose danger to the host
cell) is usually used for these purposes, and the method features
a genetic expression introduced to a cell by a ribosome. Our
methodology of the HGF genetic medication, by contrast, has
genes spiraling in "plasmid DNA" (a naked DNA technology).
Plasmid DNA alone may not be able to penetrate the cell membrane,
it can, however, generate genes if injected intra-muscularly.
The technology is extremely safe with no danger of contamination
and cytotoxicity due to ribosomes or viruses. |
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