Thanks for that additional context Mats. I did want to follow up on US vs ex-US P1 trials.
At this point, Pfizer and Moderna have consistently gotten mRNA vaccines into US trials in ~2 months after receiving a new sequence. Are the timelines to starting a trial in Australia/South Africa/elsewhere considerably shorter?
As a comment, big pharma does perform vaccine trials in the global South, although this is more about seasonality than speed. Pfizer performed a major P1/P2 trial for their RSV vaccine in Australia, because the timing of RSV season in Australia matched well with the development timelines for the drug.
One of the main arguments I see in favor of US or EU P1 trials is that the FDA/EMA are the most sophisticated regulatory agencies, and will provide more useful feedback on your development plan than other agencies. This is particularly relevant if you intend to eventually market a drug in the US, since the FDA only accepts foreign trial data if the study was conducted according to FDA requirements. Since Alvea wasn’t really targeting the US market, this is less of a consideration. Still, what do you make of this argument?
I’d also mention that once you get to the P3/BLA stage, filling in a country with a less sophisticated regulatory agency can be a burden. My own experience is that FDA/EMA/Japan are more willing to let sponsors deviate from official guidelines if there is a good scientific justification. Meanwhile, other agencies lack the expertise to assess drugs on the merits and will fall back to saying that you must follow the guidelines. For instance, I’ve been in the maddening position before of having agencies in small countries repeatedly cite FDA guidance to argue that we need to make some change to our plans, despite the fact that our drug was already approved by the FDA without said change!
Hi Matthew, thanks for engaging and for your thoughtful comments/questions.
In non-pandemic times, yes. Australia has less requirements for a IND-type submission (GMP certificate only needed prior to enrollment, not at submission); you only need the HREC approval (IRB equivalent) and no national regulatory approval (just a rubber stamp); and depending on the indication and competitive pressures you usually get faster enrollment.
Agreed. I was talking more about regulatory speed to get into FIH.
You can still get a pre-IND meeting with US regulators and get their feedback before or in parallel to conducting a AU P1 (I recommend before, but if there are few/no uncertainties you might consider in parallel). So you don’t have to choose. Agreed that FDA has requirements for foreign data, but it is a low bar (GCP, IRBs, ICs), and you could still get a majority of your data from outside the US. Rule of thumb is you need 20% of your data for an NDA/BLA to be from US populations, but even that rule has been broken successfully.
These are great points, I don’t have a lot of experience with NDA/BLA submissions to foreign countries so your insights are valuable. I’ll just note I was specifying people use Australia for P1. Agree that P2s and P3s are another ballgame.
Thanks for that additional context Mats. I did want to follow up on US vs ex-US P1 trials.
At this point, Pfizer and Moderna have consistently gotten mRNA vaccines into US trials in ~2 months after receiving a new sequence. Are the timelines to starting a trial in Australia/South Africa/elsewhere considerably shorter?
As a comment, big pharma does perform vaccine trials in the global South, although this is more about seasonality than speed. Pfizer performed a major P1/P2 trial for their RSV vaccine in Australia, because the timing of RSV season in Australia matched well with the development timelines for the drug.
One of the main arguments I see in favor of US or EU P1 trials is that the FDA/EMA are the most sophisticated regulatory agencies, and will provide more useful feedback on your development plan than other agencies. This is particularly relevant if you intend to eventually market a drug in the US, since the FDA only accepts foreign trial data if the study was conducted according to FDA requirements. Since Alvea wasn’t really targeting the US market, this is less of a consideration. Still, what do you make of this argument?
I’d also mention that once you get to the P3/BLA stage, filling in a country with a less sophisticated regulatory agency can be a burden. My own experience is that FDA/EMA/Japan are more willing to let sponsors deviate from official guidelines if there is a good scientific justification. Meanwhile, other agencies lack the expertise to assess drugs on the merits and will fall back to saying that you must follow the guidelines. For instance, I’ve been in the maddening position before of having agencies in small countries repeatedly cite FDA guidance to argue that we need to make some change to our plans, despite the fact that our drug was already approved by the FDA without said change!
Hi Matthew, thanks for engaging and for your thoughtful comments/questions.
In non-pandemic times, yes. Australia has less requirements for a IND-type submission (GMP certificate only needed prior to enrollment, not at submission); you only need the HREC approval (IRB equivalent) and no national regulatory approval (just a rubber stamp); and depending on the indication and competitive pressures you usually get faster enrollment.
Agreed. I was talking more about regulatory speed to get into FIH.
You can still get a pre-IND meeting with US regulators and get their feedback before or in parallel to conducting a AU P1 (I recommend before, but if there are few/no uncertainties you might consider in parallel). So you don’t have to choose. Agreed that FDA has requirements for foreign data, but it is a low bar (GCP, IRBs, ICs), and you could still get a majority of your data from outside the US. Rule of thumb is you need 20% of your data for an NDA/BLA to be from US populations, but even that rule has been broken successfully.
These are great points, I don’t have a lot of experience with NDA/BLA submissions to foreign countries so your insights are valuable. I’ll just note I was specifying people use Australia for P1. Agree that P2s and P3s are another ballgame.