Pharmaceutical Archives 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.