Drug trial reaction - (Drug NOT used for breast cancer)

[AlaskaAngel]

IMPORTANT: This investigational drug is NOT a drug used for HER2.

There was hope that it could be used for some cancer, as well as other diseases. Because of its relationship to the immune system and because it is a monoclonal antibody, I am posting the information about it for consideration:

LONDON, England -- Two men are in critical condition in a London hospital and four others are in serious condition after taking part in a clinical trial for a new drug.
One victim, whose head and neck were reported to have increased to three times normal size, was described by a friend as resembling "the Elephant Man."
The men were admitted late Monday to the intensive care unit from an independent medical research unit at Northwick Park Hospital after reacting badly to the drug, which is intended to treat chronic inflammatory conditions and leukemia.
The volunteers suffered extreme reactions while participating in a drug trial run by clinical research company Parexel International, based in Boston, Massachusetts.
"My 20-year-old came in here a healthy boy," the mother of one of the volunteers told CNN. "He doesn't smoke, not a big drinker, fit is a fiddle and they destroyed my son's life."
His girlfriend added: "He's in a bad way. His immune system is all gone."
The UK's Sun newspaper said one of the men had been taken to intensive care after his head and neck increased to three times normal size.
It quoted a friend as saying the 21-year-old was a student and had taken part in the trial to make money after seeing an advertisement on the Internet.
The girlfriend of another volunteer told the BBC her partner looked like the "Elephant Man" -- a freak show figure in Victorian Britain whose head ballooned outwards until his skull was wider than his waist.
She said all his internal organs were failing.
"Such an adverse drug reaction occurs extremely rarely and this is an unfortunate and unusual situation," Dr. Herman Scholtz, head of Parexel International Clinical Pharmacology, said in a statement.
Scholtz said Parexel had acted within regulatory, medical and clinical research guidelines during the study.
"We use standardized procedures for testing a drug in humans for the first time, based on a well-defined protocol, designed by the sponsor company and approved by ethics committees and regulatory authorities," he said.
Parexel said the drug, TGN1412, was an antibody developed by TeGenero of Wuerzburg, Germany.
"These events were completely unexpected and do not reflect the results we obtained from initial laboratory studies which enabled us to progress investigations into human volunteers," TeGenero's chief executive Dr. Benedikte Hatz said in a statement.
The UK medicines watchdog -- the Medicines and Healthcare products Regulatory Agency (MHRA) -- immediately started an investigation.
Professor Kent Woods, Chief Executive Officer at MHRA, told the UK Press Association: "Our immediate priority has been to ensure that no further patients are harmed.
"We will now undertake an exhaustive investigation to determine the cause and ensure all appropriate actions are taken."
Eight men had all volunteered to take part in the trial. Two were given a placebo and were unharmed.
"Two patients remain critical and four patients are serious but showing some signs of improvement," Ganesh Suntharalingam, clinical director of intensive care at Northwick Park Hospital, said in a statement Wednesday.
"The drug, which is untested and therefore unused by doctors, has caused an inflammatory response which affects some organs of the body," he said.
"The critical care team has been doing everything possible to treat the patients successfully in this unique set of circumstances. We are also collaborating closely with colleagues in the UK and overseas to draw on the skills of other specialists."


*End of news article*

This is the company's description of this drug:
Drug Development


TeGenero’s CD28-SuperMAB® have been generated to therapeutically balance the immune system in diseases associated with life-threatening abnormalities in T lymphocyte number and function. The company’s most advanced product candidate TGN1412, a fully humanized CD28-SuperMAB®, is far advanced in pre-clinical development. It has shown exquisite and unique ex vivo and in vivo T lymphocyte activating capacity and great therapeutic potential for a number of autoimmune/inflammatory as well as oncological diseases.

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 immunotherapies 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 tumor. 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, tumor-antigen specific T cells. In addition, TGN1412 has the potential to increase susceptibility of CLL tumor cells to induction of apoptosis. In summary, TGN1412 is seen as an attractive new immunotherapeutic approach that promises to enhance both cell-mediated anti-tumor immunity and induction of tumor-cell apoptosis.


Development for the treatment of rheumatoid arthritis
There is growing evidence that autoreactive 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

[Christine MH-UK]

http://www.newscientist.com/article/...al-horror.html

Apparently the drug was much less selective than other monoclonal antibodies.

Ironically, this news story seems to have made healthy, young men in Britain more interested in participating in trials because it has highlighted that they pay well and usually don't have much effect on volunteers.

Perhaps drugs companies should test such powerful drugs like they do cancer drugs: the first human trials only happen in someone with the disease who has exhausted other treatments and only one person at a time gets the treatment, at least at the start of the trial.

[Christine MH-UK]

The good news is that five of the six men who took the drug are out of the hospital. The sixth man has regained consciousness but was so badly affected by the trial that he will have to remain in the hospital for another six months and will probably have to have his hands and feet amputated, which is horrendous given that he is just 20 and had only done the trial to go on a diving vacation.

Take care,

Christine