Replies to post #6726 on Biotech Values

[krenjp]

"the average change from baseline for the six non-study eyes would surely have been greater than 0.5 lines, which is the amount reported in slide #13 from GENR's "Corporate Overview" slides."

I don't necessarily disagree with you that the value would seemingly be bigger had two patients reached 5.6 lines positive. But the value reported in slide 13 is not the average but the mean; if the distribution is not symetrical the value of the mean will be different than the average. So it is still possible to have two patients with +5.6 and a third or fourth patient at 0.5. Although this is quite a wide margin and difficult to believe but again, this is a small n.

Anyway, I wonder what you make of slide 19 on the mean VA change with Squalamine +1.1 versus Visudyne -1.1? This seems very positive, but I do not have a basis of comparison with Visudyne to say. Apparently the Visudyne data comes from their phase 3.

[randychub]

If you looked at per patient instead of per eye then it would be right on target almost with the 33%. This could be a better way to look at it since the drug would probably have a different efficacy per patient then per eye.

Randy

[rkcrules2001]

GENR 207 Comments

Dew, regarding your earlier post, some comments and questions.

1. Are we splitting statistical hairs in looking at averages across N=6 populations?

2. It seems that much of your disappointment and concern is due to comparisons with the Mexican trial. OK, there are differences. But are not the 207 40mg results still some of the best wet AMD results ever seen? Can they not stand alone?

3. The focus of your comments was on 2-Month Follow Up results. If we look at EOT results, there is strong consistency (Mean Lines Change):
.... Mexican trial Study Eye -- +1.8
.... 207 40mg Study Eye -- +1.6
.... 207 40mg 2nd Affected Eye -- +1.9

4. Clearly the 2-Month results are important, but they do not render the EOT values meaningless. For example, the 2-Month results seem to point to issues regarding the need for maintenance therapy, rather than saying that squalamine is ineffective. It’s a treatment, not a cure, right?

5. An issue I have not yet seen discussed much is Baseline Visual Acuity. As noted earlier, I believe 207 required 20/200 or better Baseline in the Study Eye. Does the EDTRS chart fully equalize results across all VA? In other words, is one line of improvement the equivalent at 20/80 and at 20/320? The same statistically, same medically, same visually? In looking at the 28 letter impact for the person with a Baseline of 20/320 (Slide 16), I just don’t see how it could be the same. Eg, could a person with, say, 20/60 ever achieve a 28-letter improvement?

6. There are significant differences in Mean Baseline VAs–
.... Mexican trial Study Eye – 20/125
.... 207 40mg Study Eye – 20/80
.... 207 40mg 2nd Affected Eye – 20/320

7. In Ihub #2140 (May, 2004) you wrote:
“However, patients with AMD do not undergo spontaneous remission. If AMD patients in a clinical trial experience improved vision during a clinical trial, the improvement can be almost certainly be attributed to the therapy.

Placebo arms in AMD trials are used to track how rapidly untreated patients lose vision –not to track how often untreated patients gain vision. The latter essentially doesn't happen.

There is no question that Squalamine works in AMD. What remains in doubt is how long the effect lasts (which dictates how often patients should be retreated) and what is the best dose to balance safety and efficacy.”

Isn’t this still where we are?