The PAVO study is basically looking at the administration of daratumumab subcutaneously.
We know that other monoclonal antibodies like Herceptin and rituximab now have subcutaneous formulations.
We, of course, cannot simply take large intravenous volumes and give them subcutaneously.
Even when you concentrate them, there’s the hyaluronidase barrier that prevents the absorption of drugs.
So the hyaluronidase enzyme that allows these monoclonals to be given subcutaneously, in the previous formulation of subcutaneous daratumumab, required mixing.
So it was a mix and deliver where the pharmacist had to mix the daratumumab with the hyaluronidase.
Here it’s a co-formulate where the two drugs have already been mixed.
What that means is a much shorter infusion time, 3-5 minutes, and it’s one of those rare things in medicine where every angle seems to be better.
So the convenience goes from a seven hour infusion to now 3-5 minutes; the infusion related reactions drop from about 40-50% to less than 12% and in terms of efficacy, although preliminary data in slightly different patient populations, the efficacy results of 56% as a single agent is really encouraging and may correlate with the fact that the pharmacokinetics of this subcutaneous administration show a higher level of cycle 3, day 1, or the trough level of daratumumab, that has been shown to correlate with efficacy in previous studies.
So the fact that this was higher than IV daratumumab is encouraging and, again, is going to be confirmed by a large phase III study comparing IV to subcutaneous daratumumab and that will be great for patients once it’s approved.