Yesterday was quite day, with one thing and another.  For starters, the FDA ODAC committee finally held a session for Cell Therapeutics pixantrone in 3rd line NHL and ChemGenenex's omacetaxine, for people with the T315i mutation in CML.  The previously scheduled meeting was cancelled due to the Snowpocalyse that hit DC last month. 

I had to dash off to a doctor's appointment myself so missed most of the action on Twitter and rushed back to catch up at lunchtime by checking Twitter buddies such as Kerri Wachter who was live tweeting from the meeting and Adam Feuerstein of The Street's excellent live blog.

:Original raster version: :Image:Food and Drug...Image via Wikipedia

You can see my original review of the February FDA documents here.  Sadly, the analysis turned out to be accurate and Adam had noted:

"That was brutal."

Approximately 20 minutes into Richard Pazdur's opening introduction. 

In particular, the FDA felt that:

"Pixantrone has demonstrated evidence of biologic activity, but the mere demonstration of biologic activity is not sufficient for approval."

Ouch!  At that point it becomes incumbent upon the company presenters to argue persuasively to the nine panel members to convince them otherwise.  However, that was going to be a tall order given the FDA concerns regarding:

  1. Neutropenia and infections were higher in pixantrone than the control
  2. Cardiac toxicity was higher in pixantrone than control, including heart failure and ejection fraction

As highlighted in the original analysis of the pixantrone filing, the FDA were also unhappy about the shortened study given only 140 people were enrolled out of the planned 320, leading them to conclude:

  1. Study was not well executed or complete.
  2. Study was inconsistent (only 8 people enrolled in the US and none had a complete response).
  3. Trial did not demonstrate statistical significance or robust findings.

What was weird about the proceedings though, was a clear disconnect between the two parties, as Adam Feuerstein reported live via the webcast:

"Pazdur: FDA not consulted about halting enrollment in trial, not pre-specified in study's statistical plan."

"Bianco: In March 2008 after 140th patient was enrolled, study was closed to enrollment. We consulted with FDA about this."

Checking my Twitter stream, Kerri reported:

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Personally, I was surprised that CTI thought that the statistical parameters would not change if they only recruited 140 of the 320 people expected and could proceed on that basis.  This is basic college level statistics – if you majorly change one input, the outliers must also be adjusted.  For this reason, the FDA's decision to treat the data as if an interim analysis had been done is fair and reasonable.

Going forward, it is likely that either all 320 patients would need to be enrolled in a study to meet the minimum FDA requirements or new studies in combination with other agents would be needed.  This latter approach is probably more likely, because the US sites (28 of them) only enrolled 8 people because the preferred treatment in the 3rd line refractory setting is combination chemotherapy, not single agent therapy. 

Perhaps the snowpocalypse last month was a portend of what was to happen.  Either way, yesterday was a bad day in DC for CTIC.

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