Roughly how many patients with ATTR amyloidosis  do you currently manage?

On a scale from 1-10 (10 being extremely excited) where would you rate your level of excitement for patisiran in this treatment population?

How do you envision an Onpattro approval for CM would change your use of tafamidis? Do you see it replacing tafamidis for any of your patients or being used in combination?

Describe the patient for whom you'd prescribe Onpattro. New patient? Patient already on tafamidis?

How important to you is Onpattro's silencer/reversal mechanism of action vs tafamidis' stabilizer mechanism?

Please give your high level view of APOLLO-B trial results

Numbers from topline results will be shared at ISA in September.  
-Is there a bar for 6mwt that will make the result clinically meaningful vs. not?

-Same question re: KCCQ scale - What number of points vs. placebo is clinically meaningful and what is the bar for a compelling benefit on this scale that would make you want to use the product (whether in combo or upfront)?

APOLLO-B included patients on tafamidis for >=6months at baseline IF they showed signs of progression while on treatment.

-What are the criteria that define disease progression while on Tafamidis?  
-What percent of your patients on tafamidis fall into this category?
-Is this the patient population you would target for treatment with Onpattro?

Alnylam says the trial was not powered or long enough in duration to demonstrate mortality benefit. P value was only stat sig on 6mwt but not the secondary endpoints on mortality and hospitalization that don't include 6mwt.  

-Will you still want to use this drug based solely on 6mwt and KCCQ?  

-Related to earlier question about effect size, will that be more important in this context of no mortality benefit demonstrated by the time of approval?

Your view of the safety profile.  
Importance (or lack thereof) of increase in arthralgia and muscle spasms on the treatment?

Implications of excluding NYHA class 3 of high risk from the trial?
- What is the standard that defines "high risk" vs. not, within class 3?
- Is it harder to improve 6mwt in this group and exclusion helped achieve positive results?- Or do they get more benefit and therefore it made the trial more difficult to show a benefit on 6mwt?
--How does the exclusion of this patient population from APOLLO-B factor into decision of whom to prescribe Onpattro?

Assuming results in September are sufficiently meaningful, how will this play in the market?  Will insurers pay for combination treatment with Tafamidis?

Administration is IV dosing every 3 weeks. Is this acceptable to patients?

Both event-based outcome measurements have nominal p value nowhere near significance. But p-value in overall group is 0.56 while in those NOT on tafamidis it is 0.99, very close to 1.  -- Does this suggest most events in the trial are happening in those on tafamidis (with progression) and therefore the sicker patients, and does this actually lend some credence to why the acoramidis trial may have failed since patients not on tafamidis and entering that trial are going to be less sick nowadays?

Could it also be the case that all the 6mwt benefit is in the tafamidis group (or the other group), and would this factor into how you choose to use Onpattro? Does the company need to break out the trend between the two groups to show whether there is 6mwt benefit in naive as well as tafamidis experienced patients to help clarify how to use the product?