a snip from the FDA Accelerated Approval Meeting

April 1, 2011

Greetings,

I'm not through the entire transcript yet (it being tax season and all), but

I wanted to copy the following section as supportive of my understanding

that regulators (the FDA) will be flexible about the study methods used for

approval based on what is feasible . the challenges of enrolling patients,

and if there is no effective alternative therapies.

Noting that randomized trials are preferred when feasible, not to make the

process more challenging, but to provide reliable information about

toxicities and benefits. Random selection in such trials eliminating patient

selection bias and usually resulting in treatment groups with equivalent

risk factors - making the assessment objective. A yes -- proven better,

instead of a maybe - needs more study.

But when there is no effective therapy to compare a drug to, then a single

arm study can suffice. ~ Karl

== " Where Nothing Works " and goal of therapy is to get to transplant

DR. WILSON: So, actually, maybe, Dr. Pazdur, you can comment. What we're

hearing is that this is a group where nothing works. So you have a drug like

clofarabine that showed a 20 percent complete response rate. If it is as

compelling as we hear, why is not a secondary confirmatory Phase 2

single-arm trial acceptable? And I'm asking this as a rhetorical question

against a randomized study.

DR. PAZDUR: I think one of the issues that we wanted to take a look at is

duration here. And if they can provide us further duration with additional

patients, this may suffice for the conversion. Here, again, we would prefer

to have a randomized trial; let's face it. And I think we've had a

discussion of what the limitations are in this population. I don't know if

or Marty want to comment on this, because they were the review staff on

it.

DR. JOHNSON: We may just very well convert this to full regular approval

based on a Phase 2 [single-arm] trial in, I think, about 60 patients. So we

may take your advice.

DR. WILSON: Well, I just bring this up because it's a little bit of a

catch-22, because as we saw in this pivotal trial, 40 percent of them did go

on to a transplant. So I think you're not going to be able to get that kind

of duration in the absence of that. And so I think you either have to accept

CR and say they had no alternative therapy, and they went to transplant and

look at the duration there or simply do a randomized study.

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