Accelerated Approval Process: Targeted Cancer Drugs

[Guest guest]

WHAT IF a highly active drug came along with very, very low - or virtually

no toxicity- that could reduce tumor burden, improve quality of life, and

prevent progression of a life-threatening type of cancer for many months and

years? .. This with virtually no side effects? Is CAL 101 such a drug, or

perhaps the btk inhibitor?

From my perspective, any drug that could demonstrate such benefits (with

virtually no risk) deserves to win accelerated (conditional) approval.

Further, if the toxicity profile is genuinely low, a placebo control could

be appropriate and ethical . in a population not requiring therapy -

asymptomatic CLL for example. (The placebo control would assist in the

objective evaluation of benefits and risks, and ethical in this case because

no treatment would not be harmful to the participants - who do not yet

require therapy).

BUT . sufficient time would be needed to make sure that unanticipated

delayed side effects do not exist for these new drugs, potentially reversing

the earlier benefit and doing substantial harm. Also, it will be important

to learn if exposure to the drug is associated with poorer outcomes later on

(compared to those not exposed to the new drug).

.. This for the benefit of patients, but also the sponsors, who would

otherwise be liable for those harms if approvals were not based on such

evidence.

The following article proposes a study design that could achieve both: more

rapid approval based on early signs of benefit, leading to full approval

based on longer-term outcomes.

Accelerated Approval Seen as Triumph and Roadblock for Cancer Drugs

http://jnci.oxfordjournals.org/content/96/20/1495.full

" The concern about how these types of approvals may affect subsequent

clinical trials led Schilsky to suggest that the system might require a

little tweaking.

The ideal situation, he said, would be an integrated approach: The

pharmaceutical company would begin a phase III trial of the new agent and

build into that trial an interim evaluation, which would occur only after

the trial had completed accrual. If a benefit appeared likely at the time of

the interim analysis, then accelerated approval could be granted on the

basis of surrogate markers. If at the end of the trial, the drug showed a

survival or clinical benefit, then full approval could be obtained. "

Also on this subject:

FDA's Next Accelerated Approval Process: " Targeted Cancer Drugs "

http://therpmreport.com/Free/f27af8ed-2215-474b-9700-fcc71e01193d.aspx?utm_s

ource=RPMel

April 09 - a bit dated but showing how Congress determines FDA policy, and

how outcomes in political struggles can support or hinder progress in cancer

research.

Karl