Posted On: 12/15/2015 8:44:00 PM
Post# of 72440
doubleJ23, thanks so much! Very much appreciated!
A few thoughts:
I'm still a bit puzzled about Brilacidin 0.6 mg/kg dosing. PK/PD modeling suggests a dose response relationship with higher doses of Brilacidin having a greater antimicrobial effect though this really isn't supported by the Phase 2b data. I thought they might consider 0.7 mg/kg to maximize drug exposure with a reasonable side effect profile.
B-OM has very stringent enrollment criteria and a fairly low bar for success. I've previously commented my belief that the trial design is perfect for preventiing oral mucositis. Brilacidin with antimicrobial, anti-inflammatory and anti-biofilm properties is perfect for this indication. Leo has to be careful that he specifies prevention and not treatment for this indication. Also, it doesn't make sense for Leo to talk about treatment of other inflammatory GI conditions without a sense that B-OM is doing what we think it's doing.
It's amazing to me that there is any positive clinical impact of once weekly Kevetrin dosing for a drug with a half life of 2-4 hours. I've mentioned this several times on the other board. I was trying to find where I talked about continuous infusion but I couldn't find it in my posts. In a note to Leo about 6 weeks ago, however, I wrote: Regarding Kevetrin, has there been any consideration to administering Kevetrin as a continuous infusion? A continuous infusion would avoid the peaks and troughs of a short half-life drug while providing constant tumor exposure to Kevetrin. Also, many of these patients already have indwelling long-term central venous access and the portable pumps have greatly improved over the last decade or so.
I'm sure more than a few people have been thinking along these lines and I believe this makes the most sense as a titratable pharmacologic strategy with the greatest chance for dramatic clinical effect. I very much hope dosing for ovarian cancer is more than twice per week.
Prurisol is still a wild card for me. I hope folks start thinking in terms of what would be considered successful for the Phase 2 trial. I think >35-40% of patients with 2 point reduction in the IGA rating represents success for the primary efficacy endpoint. This assumes a placebo response of about 20% (which could low). Lots of other considerations regarding secondary endpoints that would keep the conversation alive if the aggressive primary efficacy endpoint is not met.
Hope the above is food for thought and of course, all imo and fwiw. Thanks.
A few thoughts:
I'm still a bit puzzled about Brilacidin 0.6 mg/kg dosing. PK/PD modeling suggests a dose response relationship with higher doses of Brilacidin having a greater antimicrobial effect though this really isn't supported by the Phase 2b data. I thought they might consider 0.7 mg/kg to maximize drug exposure with a reasonable side effect profile.
B-OM has very stringent enrollment criteria and a fairly low bar for success. I've previously commented my belief that the trial design is perfect for preventiing oral mucositis. Brilacidin with antimicrobial, anti-inflammatory and anti-biofilm properties is perfect for this indication. Leo has to be careful that he specifies prevention and not treatment for this indication. Also, it doesn't make sense for Leo to talk about treatment of other inflammatory GI conditions without a sense that B-OM is doing what we think it's doing.
It's amazing to me that there is any positive clinical impact of once weekly Kevetrin dosing for a drug with a half life of 2-4 hours. I've mentioned this several times on the other board. I was trying to find where I talked about continuous infusion but I couldn't find it in my posts. In a note to Leo about 6 weeks ago, however, I wrote: Regarding Kevetrin, has there been any consideration to administering Kevetrin as a continuous infusion? A continuous infusion would avoid the peaks and troughs of a short half-life drug while providing constant tumor exposure to Kevetrin. Also, many of these patients already have indwelling long-term central venous access and the portable pumps have greatly improved over the last decade or so.
I'm sure more than a few people have been thinking along these lines and I believe this makes the most sense as a titratable pharmacologic strategy with the greatest chance for dramatic clinical effect. I very much hope dosing for ovarian cancer is more than twice per week.
Prurisol is still a wild card for me. I hope folks start thinking in terms of what would be considered successful for the Phase 2 trial. I think >35-40% of patients with 2 point reduction in the IGA rating represents success for the primary efficacy endpoint. This assumes a placebo response of about 20% (which could low). Lots of other considerations regarding secondary endpoints that would keep the conversation alive if the aggressive primary efficacy endpoint is not met.
Hope the above is food for thought and of course, all imo and fwiw. Thanks.
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