Replies to post #8070 on Biotech Values

[rkcrules2001]

GENR results... Question
<<For the 4 median patients taking 40 mg doses and combining both eyes, there was an average dropoff of about 1 letter per month between 2 and 4 months. This is approximately the same rate of vision loss as shown for untreated patients in an earlier slide.>>

A couple of points.

First, I think you are rounding a bit.

If I understand, you are calculating the combined results of 40mg Study Eye and Second Eyes at 2 months and 4 months. Would this be

2 Month : (2.8 + 2.9) / 2 = +2.85
4 Month : (-1.5 + 3.9) / 2 = +1.2
Dropoff : 2.85 - 1.2 = 1.65

Wouldn't 1.65 be the dropoff over 2 months, so the average monthly dropoff would be .83? Or am I misunderstanding the math?

I believe the 304 Sham patients in the 2 recent Macugen trials averaged a loss of about 1.2 letters per month. I'm getting this from slides 15 & 16 in the FDA August Macugen meeting ( http://www.fda.gov/ohrms/dockets/ac/04/slides/2004-4053S1_05_FDA-Harris.ppt )

As we've discussed before all this may be academic with only N=4 (or even 6), but on a percentage basis .83 versus 1.2 may still be notable.

Second, how "compelling" one finds these results may depend on what's expected of squalamine (I don't know how to spell Evizon yet). Keep in mind these 2-month and 4-month results are after treatment had been discontinued.

If one is expecting a cure after treatment, then these results are disappointing. However, if squalmine is expected to become an ongoing therapy that keeps a devastating disease in check (or even regresses it), then these results may be pretty darned exciting.

I believe people treated with Macugen still suffered an average loss of .7 letters per month while undergoing treatment every 6 weeks.

And squalamine results (even at 10mg) blow that away.

[rkcrules2001]

Question for Winchem

My prior statement about "even 10mg squalamine blowing away" Macugen is not really correct. I kept thinking about the published 10mg N=6 average at EOT of -.8, versus the +2.7 you calculated when the high and low results are thrown out. This led me to attempt to reproduce your calculations, and I came up with some differences. In particular, the +2.7 10mg EOT number changed to +.3. That's still better than Macugen's apparent average of -.7, but it's not realy "blowing away".

Below are the numbers I came up with, but again I'm not certain my formulas are correct. Would you please reassess your adjusted 10mg EOT number, and see if you get +2.7 or +.3? Am I doing something wrong?

Here are my numbers....

Date       Mex  40mgst   40mg2nd  10mg 
 Wk3        6.3   6.9       4.3     0.8 
 EOT        8.6   7.8       7.1     0.3 
 2Mon       6.7   2.8       3.3    -2.0 
 4Mon       5.5  -2.0       4.0    -2.7

These numbers would produce a revised average 40mg 2Mon-to-4Mon dropoff of 1.0 letter per month (versus the .83 in my earlier post), which is exactly what you said originally. A monthly loss of 1.0 letters is still better than the 1.2 average loss for folks going without any treatment, but it is even more hair-splitting, especially considering the low Ns.

Just for ref, here are your original numbers...

Date  Mex  40mgst 40mg2nd 10mg 
 Wk3   6.5   6.9     4.3	   0.8 
 EOT   8.8   7.8     7.1    2.7 
 2Mon  6.9   2.8     2.9   -1.9  
 4Mon  5.7  -1.5     3.9   -2.0