Stringent Path for Accelerated Cancer Drug Approval, et al

[Guest guest]

February 14, 2011

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The FDA’s Oncologic Drugs Advisory Committee (ODAC) met last week to debate the

value of the FDA's accelerated approval program for cancer drugs. The goal of

the accelerated program is to provide novel and promising treatments to patients

faster than through the traditional, longer route to FDA approval. Successful

accelerated approval drugs include Gleevac, the oral drug for chronic myeloid

leukemia, as well as most HIV treatments.

Accelerated approval is granted based on a surrogate endpoint study rather than

the gold standard of overall survival, bona fide clinical efficacy, or quality

of life improvement. Surrogate endpoint trials are generally faster than the

traditional efficacy trials that are required for full drug approval because the

surrogate endpoints are typically laboratory readouts that are available before

direct measure of effectiveness. More.............

http://tinyurl.com/4ab7phq

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MULTIPLE KINASES

Kinase inhibitors are the largest class of new cancer drugs. However, it is

already apparent that most tumours can escape from the inhibition of any single

kinase. If it is necessary to inhibit multiple kinases, how do we choose which

ones? In this Opinion article, we discuss some of the strategies that are

currently being used to identify new therapeutic combinations of kinase targets.

Despite the excitement surrounding these targets, clinical progress has been

uneven. Kinase inhibitors have revolutionized the treatment of a select group of

diseases, such as chronic myeloid leukaemia (CML) driven by a single oncogenic

kinase; for these conditions, kinase inhibitors have achieved multi-year

increases in survival.

Why has clinical progress been so challenging? One reason is that most tumours

can escape from the inhibition of any single kinase. This first became clear

when resistance mutations in BCR–ABL were discovered in patients with CML who

were resistant to imatinib; similar mutations have now been detected in other

kinases following treatment with kinase inhibitors. Alternatively, tumours can

acquire drug resistance through mechanisms that do not involve mutation of the

target. These mechanisms include the activation of surrogate kinases that

substitute for the drug target and the inactivation of phosphatases to amplify

the residual kinase activity that persists during drug treatment. It is also

clear that many tumours possess intrinsic resistance to kinase inhibitors at the

time of initial therapy. This can result from the activation of multiple,

redundant kinase signalling pathways or the presence of activating mutations in

downstream pathway components, such as KRAS or PTEN, which enable the tumour to

bypass the drug target. Read more...........

http://tinyurl.com/4pmrbpz

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FYI,

Lottie Duthu