AP24534

[Guest guest]

Dear Jeff,

I do know that there is an Ariad trial in the Phase 1 going on at MDACC and

I believe at the Univ. of Michigan with Dr. Talpaz and at OHSU. The only thing

my doctor has told me was that it was a very low dose and would not consider

putting me in it until they raise the dose in Phase 2. The could always lower

it in Phase 2, but they cannot raise it in Phase 1 because it is the first human

trial.

Here is breaking news from the ASH convention held last week in San

Francisco about AP24534.

AP24534, even when studied in modest concentrations, completely

suppressed the emergence of resistant mutants. This finding is in direct

contrast to results obtained with all other Bcr-Abl inhibitors previously

profiled in this in vitro assay. This resistance profiling method has previously

predicted the specific mutations that confer clinical resistance to marketed CML

therapies: imatinib, dasatinib and nilotinib. CML is characterized by an

excessive and unregulated production of white blood cells by the bone marrow due

to a genetic abnormality that produces the Bcr-Abl protein. After a chronic

phase of production of too many white blood cells, CML typically evolves to more

aggressive phases such as accelerated or blast crisis. Treatment with Bcr-Abl

inhibitors is initially effective in most patients but frequently results in the

emergence of Bcr-Abl mutations that confer drug resistance over time. The T315I

mutant of Bcr-Abl currently accounts for 15-20 percent of all drug resistant

mutants in CML. First-generation therapies for CML, such as imatinib, and

second-generation therapies for CML, such as dasatinib and nilotinib, are not

able to inhibit this mutated protein and thus are not effective against all

forms of CML. For the entire article, go to this site:

http://www.genengnews.com/news/bnitem.aspx?name=46823730

I hope this answers your questions.

Blessings,

Lottie

[Guest guest]

Thank you very much, this is helpful, Jeff

>

> Dear Jeff,

> I do know that there is an Ariad trial in the Phase 1 going on

at MDACC and I believe at the Univ. of Michigan with Dr. Talpaz and

at OHSU. The only thing my doctor has told me was that it was a

very low dose and would not consider putting me in it until they

raise the dose in Phase 2. The could always lower it in Phase 2,

but they cannot raise it in Phase 1 because it is the first human

trial.

>

> Here is breaking news from the ASH convention held last week

in San Francisco about AP24534.

>

> AP24534, even when studied in modest concentrations,

completely suppressed the emergence of resistant mutants. This

finding is in direct contrast to results obtained with all other Bcr-

Abl inhibitors previously profiled in this in vitro assay. This

resistance profiling method has previously predicted the specific

mutations that confer clinical resistance to marketed CML therapies:

imatinib, dasatinib and nilotinib. CML is characterized by an

excessive and unregulated production of white blood cells by the

bone marrow due to a genetic abnormality that produces the Bcr-Abl

protein. After a chronic phase of production of too many white blood

cells, CML typically evolves to more aggressive phases such as

accelerated or blast crisis. Treatment with Bcr-Abl inhibitors is

initially effective in most patients but frequently results in the

emergence of Bcr-Abl mutations that confer drug resistance over

time. The T315I mutant of Bcr-Abl currently accounts for 15-20

percent of all drug resistant mutants in CML. First-generation

therapies for CML, such as imatinib, and second-generation therapies

for CML, such as dasatinib and nilotinib, are not able to inhibit

this mutated protein and thus are not effective against all forms of

CML. For the entire article, go to this site:

>

> http://www.genengnews.com/news/bnitem.aspx?name=46823730

>

> I hope this answers your questions.

> Blessings,

> Lottie

>

>