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

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

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

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

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 - Is there a stat sig change vs. placebo that is NOT clinically meaningful and if so what is the bar for a compelling benefit?

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 previous question about effect size, will that matter more in the 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?

What is the implication that NYHA class 3 of high risk was excluded from the trial?
Is it harder to improve their 6mwt and thus helped achieve positive results?Or would they get the most benefit on 6mwt and therefore it actually made the trial more difficult to show a benefit?
In the context of who you might put on Onpattro, does this limit its use, and are these not the patients who may need the most help beyond tafamidis?   Will you also not treat Class 3 high risk with Onpattro?

Assuming the results in September are sufficiently meaningful, how will this play in the market?  If used as a combo with tafamidis, will any insurers pay for that?

administration is IV dosing every 3 weeks. Is this reasonable for 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 are happening in those on tafamidis (with progression) and therefore 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?

Rate your level of excitement about patisiran for ATTR Amyloidosis with Cardiomyopathy on a scale of 1-10 and provide the rationale.

How important to you is Onpattro's silencer/reversal ability vs tafamidis' stabilizer claim?