Innovation Pharmaceuticals Inc (IPIX)

[sunspotter]

"he continues to equate hypertension and tingling with actual more meaningful SAEs"

Hypertension and peripheral neuropathy (nice spin by IPIX to term it "numbness and tingling" but let's call a spade a spade and acknowledge the truth) are both potentially very serious, as most people with some knowledge of medicine and therapeutics know.

Here's another well-informed commentator talking about the AE profile of brilacidin:

"More important and of concern is the fact that numbness and tingling are still extremely frequent AEs (58-74%) in the Phase 2b trial despite the dose reduction. The syndrome has been described as “paresthesias, usually beginning in the oral area, and often with subsequent extension to one or more of the following areas: face, scalp, extremities, upper thorax, and/or perineum (groin and buttocks)”; the company refers to it as an ‘ion channel effect’ of short duration and reversible. [3]

In the context of the blood pressure changes observed in Phases 1 and 2, this ‘ion channel effect’ may be anything but trivial. Electrophysiologic studies on human cell lines published in abstract form found that even low concentrations of brilacidin (1µM) block ion channels to a significant degree: 43.2% (ASIC1a), 56.3% (hNav1.7) and 45.8% (hKv1.6).[4] In case you are interested, ASIC1a stands for acid-sensing ion channel, and hNav1.7 and hKv1.for the sodium and the potassium channel, respectively.

Adverse Events like hypertension, numbness and paresthesia seem to be caused by inhibition of Na, K and other ion channels

This Kv1.6 channel is expressed not only in neurons, but also in cardiac and other muscle tissue where it affects membrane potential and cellular response to stimuli [5]. While ion-channel blockers are an area of considerable interest for drug therapy, we are not convinced such off-target effects are desirable for an antibiotic. Even if it is a QIDP drug.

Clearly, a thorough QT study with brilacidin showing no major QTc prolongation would go a long way to set everyone at ease. Such a study has not been done yet. However, we were surprised to find a trial of brilacidin ORAL RINSE listed on clinicaltrials.gov. Interestingly, patients with EKG abnormalities, hypertension, and QT prolongation are specifically excluded from participation in this trial, although brilacidin is only given topically.

What do we really know about brilacidin / PMX-30063? Given the dearth of published information, and the total lack of peer-reviewed publications, the answer is: Really not much. Abstracts and presentations by PolyMedix and Cellceutix, the new owner of brilacidin, from various conferences are uniformly selective, redacted and incomplete. [6,7], " (The emphases are mine.)

http://allphasepharma.com/dir/2015/07/10/1693/brilacidin-qidp-drug-at-a-critical-juncture/