TD:
There is nothing inherently wrong with T cell depletion. We have more T cells that we need, day to day. If one were to selectively deplete a subpopulation aside from antigen-activated cells, that might be "unwanted". If MEDI (BGEN, for LFA3tip) shows that there are no adverse events (infection would be a primary concern), then no sweat.... you discontinue treatment if cell count drops too far.
However, if I were a psoriasis patient, I'd prefer to avoid it. And, until proven otherwise, it's a pink flag.
>> 1) Would the dosing regimen necessarily be the same for psoriasis as for RA? <<
I would expect the effective dose for psoriasis to be ballpark the effective dose for other autoimmune diseases. However, the potential magic in 507 is in Dumont et al.-like results (including independent results from MEDI, showing a different mechanism but similar message), not in making people 20% better by depleting 20% of their T cells. That's why it is of interest to determine the minimal amount of antibody that is effective.
Again, results from the small i.v. phase IIa did not show a dose response. Approximately 1 mg/recipient was as effective (or more effective!), mean reduction PASI, as higher doses. The number of recipients per treatment group was insufficient, however, to draw conclusions. MEDI had, honestly, done too little too late. They're trying to make up for that now. We'll see if they used a little wisdom this time.
>> 2) "If" they actually undertake clinical trials with this new indication, would it not be safe to assume that at least they have some anecdotal evidence that the depletion issue isn't that great? <<
Yes, but the AC meeting for LFA-3tip will provide light on concern, and MEDI's judgement re. 507 is -- IMO -- pure crap.
>> 3) Concerning the start of the retreatment studies, would it not be logical to assume that MEDI had to provide some data to the FDA for them to approve such retreatments and if so, wouldn't an issue of depletion preclude such retreatments? <<
No. Trials that show T cell depletion are nothing new to the world of biologicals. As long as depletion is not deep and long-lasting, side effects have not been pronounced. For psoriasis, it's a concern. Again, we'll see how much of a concern when we hit the LFA-3tip AC.
I'd like to avoid depletion if I were a patient, but it wouldn't stop me from seeking treatment with a LFA-3tip or a 507. |
