Please describe your clinical practice. Roughly how many patients with ALS do you currently manage?

What are your initial thoughts on the clinical trial data and scientific literature to date for AMX0035?

On a scale from 1-10 (10 being extremely excited), how would you rate your level of excitement for  AMX0035?

If AMX0035 gets approved on the existing data available so far, do you expect to begin prescribing AMX0035 to any of your patients?

How does AMX0035 compare and fit in with the current standard of care or other treatment options?

The Adcom voting question tomorrow: (Do the data from the single randomized, controlled trial and the open-label extension study support a conclusion that sodium phenylbutyrate/taurursodiol is effective in the treatment of patients with amyotrophic lateral sclerosis (ALS)?)

If you were on the panel, how would you vote

If you are a NO on the Adcom voting question, how would you answer the followup question which is, "what additional information you would consider necessary to support a conclusion that sodium phenylbutyrate/taurursodiol is effective in the treatment of patients with ALS"

In briefing docs, FDA expressed a few of its major concerns on the primary analysis:
1. mITT, excluding the 2 deaths. (appropriateness of "joint rank" vs. shared baseline mixed effects model used by Amylyx for the analysis)
2. Missing data on week 24 from live patients and how to treat this missing data. (MAR method vs. LOCF by Amylyx)
3. Linearity assumption of ALSFRS-R scale.  

How much weight do you give each of these concerns in terms of how you view the trial results?

When FDA analysis applied, p values go from stat sig 0.038 to 0.06 and 0.08
Does it change your overall view of the product?
Do you believe as a single trial this is still sufficient for an approval? Or does it make you want to see a larger 2nd trial first?

How do you think the adcom experts will be impacted by these FDA presentations and how do you predict they will they vote?

Thoughts on composition of the expert panel

On Secondary endpoints
Is this data encouraging?  Not helpful?Numerical trend going against treatment in pNF-H   32.7 pg/mL
Is that large? Small? Meaningful?Numerical difference in rate of SVC decline *in favor of treatment*, of 5% p= .076
Is it meaningful?

Is ATLIS baseline imbalance contributing to slower rate of decline in treatment group?

Overall view on secondary endpoint data

FDA also raises the issue of the analysis ignoring deaths in open label extension study, when analyzing the ALSFRS slopes, as with primary endpoint.
Is this a real issue?  Or always part of ALSFRS-R analysis?
- Is this different from Radicava which got approval on ALSFRS slope?  
Is this more of an issue because it is a single trial vs. 2 trials?

FDA raises the issue of Unblinding due to GI and bitter taste--- FDA shows gastrointestinal AEs in first 3 weeks, but it's only around 33% vs. 21%. From your experience is this a difference that is likely to unblind a trial? Is this possibly a less pressing issue being raised by FDA? Or is it important?  Are you concerned about unblinding in the trial when you consider these trial results?