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pharmaceutical news
Drugs
trial patients start to
improve
19th March 2006
TWO of
the
six men involved in a drugs trial that went disastrously wrong
were last night still in a critical condition. However, doctors
said yesterday that the condition of the other patients was
improving, that they are conscious and able to talk to their
families.
A
human medical experiment goes horribly
wrong in
TGN1412
drug trial
March 16th
2006
Two
men who fell seriously ill following a clinical drugs trial
remain in a life-threatening condition but four others are
showing signs of recovery.
All six are still in intensive care in Northwick Park Hospital,
north-west London, after falling ill on Monday.
TeGenero the manufactures of the anti-inflammatory drug, says it
has apologised to the men's families.
TeGenero described the reactions as "shocking developments" and
said the new medicine had showed no signs of problems in earlier
tests.
Clinical Director of Intensive care Ganesh Suntharalingham at
Northwick Park Hospital said: "Of the six patients admitted to
critical care, the four who are seriously unwell are continuing
to show signs of improvement but it is still early days.
"The other two men remain critical and it could be a while
until they show significant change."
One of the critically ill men has been named as student Ryan
Wilson, 21, of Highbury, north London.
Another who was taken seriously ill has been confirmed as a New
Zealander. The New Zealand High Commission said he was
"conscious and has spoken to hospital staff".
TeGenero
AG
Statement TGN1412
March 17th 2006
“We are encouraged by the signs of progress in the conditions of
the patients but remain deeply concerned for them and their
families. They are receiving excellent treatment at Northwick
Park Hospital in London.
We are working closely together with the doctors and have made
ourselves available to answer any questions on the drug and to
support them in choosing the most suitable treatment.
At the same time, we have offered every support possible to the
institutions in charge of investigation, the MHRA in the UK and
the German authorities. We will respond to any questions and
provide information beyond the material already available. We
are doing everything we can to unravel as quickly as possible
how these unexpected symptoms could have developed.
The tested substance TGN1412 is a new treatment for the
devastating illnesses of leukaemia, rheumatoid arthritis, and
multiple sclerosis.
We are shocked about the symptoms we have seen in the
volunteers. Extensive pre-clinical tests showed no sign of any
risk. We observed strict standards for this clinical test and we
obtained all required approvals both in Germany and in Great
Britain. The drug was tested extensively in laboratories and has
been tested on rabbits and monkeys. We saw no drug related
adverse events and there were no drug related deaths.
Our thoughts are with the patients and their families.”
Dr. Thomas Hanke
Chief Scientific Officer
Information
Supplied by TeGenero AG
TGN1412
Development
of TGN1412 for the treatment of B-CLL
Despite clinical
benefits from chemo-or monoclonal antibody therapy, B-cell
chronic lymphocytic leukaemia (B-CLL) is still an incurable
disease and the development of novel additional immunotherapy is
for the treatment of B-CLL is highly requested by
hemato-oncologists. TGN1412 represents a novel class of
immunomodulatory antibody and has demonstrated the potential to
be effective in the treatment of B-CLL in pre-clinical trials.
Several features of this disease suggest that immune-based
strategies have therapeutic potential. Whereas the clinical
course of B-CLL often remains stable for years, the total
leukemic cell burden tends to expand at variable speed without
any apparent reaction of the immune system against the tumour.
It has been shown that this is related to an impaired T cell
mediated immune response. Despite expressing high levels of
major histocompatibility complex (MHC) class I and II molecules,
CLL B-cells are ineffective antigen-presenting cells (APC).
Moreover, CLL B cells tend to be resistant to activation-induced
cell death, (apoptosis).
It has been shown by the Company that activated T cells can
induce CLL B-cells to become effective APCs, making these cells
“visible targets” for endogenous, tumour-antigen specific T
cells. In addition, TGN1412 has the potential to increase
susceptibility of CLL tumour cells to induction of apoptosis. In
summary, TGN1412 is seen as an attractive new immunotherapeutic
approach that promises to enhance both cell-mediated anti-tumour
immunity and induction of tumour-cell apoptosis.
Development
for the treatment of rheumatoid arthritis
There is growing
evidence that auto reactive T cells are involved in the
pathogenicity of chronic inflammatory diseases such as
rheumatoid arthritis (RA). RA is a debilitating, chronic
inflammatory disease of the joints that affects approx. 1% of
the population. Despite recent advancements with novel therapies
such as TNF-α-blockers aiming at neutralization of inflammatory
mediators, complete remission is rarely gained. Thus, there is
still a high medical need for efficacious and well-tolerated
novel treatment options in RA.
A pronounced T-cell activation and expansion mediated by
CD28-SuperMAB® in animal models is accompanied by the expression
of anti-inflammatory cytokines, like IL-10, rather than by the
toxic cytokine storm of pro-inflammatory mediators induced by
other agents that address the TCR complex. CD28-SuperMAB®
over-proportionately expand regulatory T cells, a specialized
T-cell subset that suppresses auto-aggressive T-cells present in
the body and which has only recently been appreciated as
important guardians of immune tolerance. Based on their
functional potency in suppression of organ-specific as well as
systemic autoimmune diseases, regulatory T-cells have been
widely accepted as attractive targets for immunotherapeutic
intervention. However, attempts to expand and activate this
subset of CD4 T-cells in vivo and, ultimately, in
autoimmune/inflammatory diseases have been hampered so far by
the lack of therapeutic agents.
The pronounced regulatory T-cell expansion and induction of
anti-inflammatory cytokines by CD28-SuperMAB® are mechanistic
explanations for beneficial effects of CD28-SuperMAB® in animal
disease models for human autoimmune/inflammatory diseases.
Multiple preclinical results indicate that CD28-SuperMA® are
capable of inhibiting clinical signs, surrogate parameters and
pathophysiological characteristics of autoimmune/inflammatory
diseases in a well-tolerated fashion.
Thus, TGN1412 is a promising novel approach to addressing the
medical need in chronic autoimmune/inflammatory diseases, which
require long-term therapy without severe side effects.
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