AstraZeneca PIIIb trial update for Bevespi in COPD

[idpickering]

AstraZeneca today announced top-line results from the AERISTO Phase IIIb trial for Bevespi Aerosphere (glycopyrronium/formoterol fumarate) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). In the trial, Bevespi Aerosphere demonstrated non-inferiority to umeclidinium/vilanterol on peak forced expiratory volume in one second (FEV1) but did not demonstrate superiority on peak FEV1 or non-inferiority on trough FEV1.

https://www.investegate.co.uk/astrazene ... 00056227Y/

[moorfield]

Thanks Ian, but wtf does that one mean do you reckon? Is it working or not, my directorspeak translator is misfiring this morning ....

I hope the next dividend is going to be demonstrating non-inferiority to inflation

[idpickering]

Thanks Ian, but wtf does that one mean do you reckon? Is it working or not, my directorspeak translator is misfiring this morning ....

I hope the next dividend is going to be demonstrating non-inferiority to inflation

My take on it is that it is working.

Ian.

[Julian]

Thanks Ian, but wtf does that one mean do you reckon? Is it working or not, my directorspeak translator is misfiring this morning ....
...

This AZ drug is already approved for COPD in the USA & Canada and is going through the EU approval process with a decision expected this year. It works (it wouldn't have got FDA approval if it hadn't demonstrated efficacy) but there is now conflicting evidence as to whether it is more effective than the GSK competitor that got EU approval in 2014 ("The performance of Bevespi Aerosphere in AERISTO is inconsistent with previous data" where I assume that previous data is from earlier phase III trials).

AZ themselves seem confused as to why these latest trial results are inconsistent with the previous data which I assume, given they flag some inconsistency, showed stronger efficacy data than was seen in this latest trial. It is possible that after re-analysing the data AZ might find an explanation, maybe something odd about this cohort vs the previous phase III trials that were over 4 times bigger. If the data stands then I don't think it would undermine the EMA approval (someone correct me if I'm wrong but I don't think superior performance against a comparator is required for approval) but it would be a disappointment for AZ in terms of the sales prospects in the EU if/when this new product is launched launch because I'm sure that AZ were hoping that a positive outcome from this comparator study, one that showed a statistically significant increase in efficacy vs the GSK competitor, would have provided a very powerful sales tool for their salesforce.

TL;DR - it works but we might not be on course to develop as strong a sales message as we had hoped both for ongoing US/Canada sales and as it gets licensed in other parts of the world.

- Julian

[tjh290633]

I wonder why they had to do a fresh set of trials? Does the EU not accept trials carried out in non-EU places?

TJH

[Gengulphus]

Thanks Ian, but wtf does that one mean do you reckon? Is it working or not, my directorspeak translator is misfiring this morning ....

Wrong tool for the job - what you actually need is a regulatorspeak translator! ;-)

Gengulphus

[Julian]

I wonder why they had to do a fresh set of trials? Does the EU not accept trials carried out in non-EU places?

TJH

No, the EU (European Medicines Agency) accepts non-EU trial data but only if those trials have been conducted such that they conform with EMA guidelines. Big pharma is very wise to this so, even if all of the original phase III work was non-EU, I would have expected it to be EMA-compliant data.

In calling this a "fresh" trial it is worth clarifying that this wasn't "fresh" as in a replacement for the previous trials. The previous trial data will have had to have been submitted to get the EMA review process started. This additional trial is supplementary data to add to the phase 3a data from the previous trials that would already have been submitted to the EMA. This additional trial might have been because the EMA wanted more data for statistical and/or safety reasons and/or because AZ might have been so encouraged by the efficacy readouts that it was seeing from the initial phase 3a trial data that it wanted what it expected to be a strong comparator study in the bag for EU product launch. These sort of comparator studies are done all the time but if they are prior to drug approval in a region they are called phase 3 studies(*) and if they are after approval they are called phase 4 studies.

- Julian

(*) Phase 3b in this case because it was conducted after the new drug application (NDA) with initial phase 3a trial data had already been submitted to the EMA.

[tjh290633]

Thanks for that explanation, Julian

TJH

[Julian]

You're welcome Terry.

For full disclosure - I am not a pharmacologist and I don't work in the industry but by some strange twist of fate more than half of my closest friends are pharmacologists so I have spent the last 3 decades or so often being the lone non-pharmacologist (I'm a computer guy) sitting in pubs and at dinner tables listening to a bunch of pharmacologists talking shop and annoying the hell out of them by asking lots of questions both during and after such conversations trying to understand at least some of it so all my knowledge is second-hand.

Interestingly enough I was out with one of those friends on Wednesday night, the night before Ian posted the news, and she told me that work had suddenly got very busy. What's interesting about that is that she actually works in clinical science(*) for AZ and has recently become heavily involved in the COPD side of things. I'm wondering if she might even be part of the team that has been drafted in to try and analyse the anomalies between the various phase 3 trial data! If so then I'll obviously not be able to find out any inside info about any specifics but I will at least ask her if she is on that project.

- Julian

(*) Those are the people who design, run and review/analyse data from clinical trials