Let's look at the cons from the presentation:
IV administration
Is this really a con? Many of these ABSSSI patients are quite sick upon arrival in the ER. (TIAB, I'm sure you have some observations.) Most will get IVs when blood is drawn for laboratory studies. It's hard for me to see how a single dose Brilacidin through an in situ IV is a 'con' in any way, especially since the IV route is the fastest route to get a blood level of antibiotic for treatment of severe infection. Also, with single dose treatment it's just not an issue.
• small Vd
Previously addressed. With a small Vd, infections where there is very poor perfusion may not get adequate tissue levels (MIC) to effectively treat the infection. Vd is a consideration in critically ill ICU patients who appear to have a larger Vd and may require higher doses of certain drugs. Again, Brilacidin Phase 2b suggests the drug is quite effective for the indication tested (ABSSSI). Perhaps a small Vd will limit its usefulness for other as yet untested indications. I think it's more of a theoretical consideration at this point and a possible limitation as opposed to a 'con.'
• gender differences in PK (Cl and body surface)
Previously addressed. This one surprised me as we have not seen any indication that gender differences impacted clinical results. The more detailed data for Brilacidin Phase 2b does not focus on gender differences and it does not appear to be a major issue in moving forward with Phase 3. I think the important point about gender differences in drug dosing is that they are real and may impact dosing for some drugs. It is a consideration in moving forward with trials for any drug. Is gender difference a 'con' if overall effectiveness and adverse effects are comparable in the study population? I don't think so.
• reversible adverse effects
(paresthesia, ? blood pressure and heart rate)
Also addressed. This is a 'con' but doesn't appear to be limiting.
First, note the the systolic blood pressure (SBP)cutoff decreased from 180 to 160 from Phase 2a to 2b. Second, consider that a significant percentage of the population presents to the ER with (SBP) > 160. I'm more interested in the change in SBP during infusion to see if SBP changes are really a con and how significant it might be. I have not found any information suggesting change of heart rate with Brilacidin infusion so I'm not too concerned that this is a problem. Also, most ABSSSI patients have significant fever, which as you know, is usually associated with a more rapid heart rate. Again, is there a change in HR during infusion that is concerning? Neither Phase 2a or 2b in any way suggests that this is a problem so I don't think change in HR is a real 'con.'
Paresthesias are the one adverse effect that I was most concerned about. Apparently, the paresthesias are mild and transient and related to sodium channel blockade. In that the paresthesias don't persist and Brilacidin appears generally well tolerated, I see paresthesia as a 'con' as it is an adverse effect. In that the drug is well tolerated, I see it as a weak con that will not limit Brilacidins clinical usefulness.
Hope this helps.
