Innovation Pharmaceuticals Inc (IPIX)

[slcimmuno]

on the BMJ ABX piece, i put an email out to the author letting him know there *is* a different kind of ABX in the works (not run of the mill). one that is, yes, QIDP-designated; and one that is, yes, effective against MRSA. (he kind of dissed this; MRSA still is killing lots of folks in non-Western parts of the world esp.) and it goes by the name Brilacidin, part of a larger class of compounds referred to as HDP-M --- novel anti-infectives highly resistant to resistance.

doubt i'll get a response but just wanted to flag him on it. (see the email i sent, at bottom.) the BMJ does allow Rapid Responses, so if there is anyone who wants to take a stab at that, feel free.
http://www.bmj.com/content/350/bmj.h1500/rapid-responses

all in all i thought his contrarian observations were insightful and he asked fair Qs of ABX companies, of IDSA, of the FDA about the QIDP process, trial data and results, etc. he is a bit of an activist type... see link to NYT piece---him marshalling folks to get Big Pharma to open up data.
http://www.nytimes.com/2013/06/30/business/breaking-the-seal-on-drug-research.html

anyway, hopefully B and HDP-M resistant-to-resistance (be it unlikely, futile) advantage will get its due---its MOA a key differentiating factor. not to mention our lead compound has performed on par w/ the best ABSSSI drug out there (which is becoming less effective due to resistance) and w/ a better safety profile (fewer side-effects). the single-dose aspect does have real clinical (better compliance) and monetary consequences (major bucks saved, to the tune of $1800 shaved off for 1 day less in LOS) that i think he downplayed, glossed over, when discussing Orbactiv.

of note: the BMJ ABX piece was part of a larger critique by the Journal Q'ing the Need for Speed---expedited approval. see below.

Commentary: Will 20th century patient safeguards be reversed in the 21st century?
http://www.bmj.com/content/350/bmj.h1500

EXCERPT
Despite numerous changes in White House and Congressional leadership, the 21st century has seen a steady escalation of legislation chipping away at the FDA. In response to legislative and political pressure, the FDA has offered numerous concessions to industry and its lobbyists. It now offers four pathways to speed the approval process for many drugs and biologics6 as well as an easier approval pathway for drugs for orphan diseases (those affecting fewer than 200?000 patients in the US).7 Though all drugs are supposed to meet “appropriate standards” for safety and effectiveness, the standards for most drugs approved through expedited pathways are clearly lower, with smaller and shorter term studies than are otherwise required. For example, in 2008, an average of about 100 patients were tested with new drugs that were approved through expedited pathways, compared with almost 600 for standard approvals.8 As a result, patients relied on drugs for which safety and effectiveness were not always confirmed when they were first on the market. Instead of requiring clear proof of safety or effectiveness before approval, most evidence is not required until afterwards. Sadly, “required” postmarketing studies are often delayed for years,9 and when problems are discovered, corrective action doesn’t happen swiftly. It takes on average 11 years after approval for the FDA to institute new black box warnings, rescind approval, or require new risk information or contraindications be made public.8

xxxxxx

i can understand Leading Light MDs like those at the BMJ and elsewhere expressing caution (First, Do No Harm), but still.... seems to me the science (Prec Med) is getting good enough that certain populations, those patients w/ the worst diseases (cancers) and baddest bugs (infections), deserve expedited access to the best meds via actual full-on approvals---by way of smaller, more focused studies. all the Right to Try state-level legislative efforts barnstorming the country is indicative of mounting patient demand.

anyway, i see this article as a "Hold On a Sec", a raising of the Yellow Flag. Cautionary. but i don't see any brakes being pressed down upon... too much pressure, for so many good reasons, for Congress/the FDA to continue expediting drug development.

MY EMAIL

Dr Doshi,

A very interesting read. Appreciate that you took a contrarian position -- you ask many good questions and raise valid points. Insightful.

One US-based biotech company that is doing innovative work on the ABX development front is Cellceutix. Its lead compound, Brilacidin, and other Host Defense Protein-Mimics (HDP-M), stands a good chance of becoming a truly novel, first-in-class anti-infective.

The early clinical work was done at U Penn (PolyMedix) under chem/quant visionaries (William DeGrado, Michael Klein, Richard Scott, Gregory Tew). Cellceutix acquired rights to Polymedix IP and other assets in 2013. The therapeutic approach not only mimics, but improves, the immune system's natural response with the drug perforating bacterial walls quickly. As a result of this mechanism (rapid lysis), resistance is much less likely to develop, if at all. These synthetic molecules are smaller, more stable, more potent, and more selective compared to natural HDPs.

The FDA has granted Brilacidin QIDP status and, unlike other ABXs that have shown potential still in pre-clinical stages (e.g., Teixobactin), it's in human trials. Its Ph 2b results were comparable to Daptomycin for ABSSSI but as a single dose (not 7 days, like Cubicin). It also is active against MRSA infections. Work being done by Cellceutix at Fox Chase Medical Center on other gram negative bugs--as you know the hardest to kill--is very promising.

HDP-Mimics, in general, have anti-inflammatory and anti-biofilm properties, with some additional Cellceutix compounds effective against malaria and drug-resistant strains of tuberculosis . The company will be providing an update on aspects of its ABX pipeline at ECCMID 2015, to be held in Copenhagen, at the end of April.

If not already on your radar, the company's progress might be worth tracking, particularly because its unique MOA might make resistance much less likely perhaps even moot (see the Polymedix slide deck below). Maybe you could dig deeper on the potential of HDP-Mimics in a future article if you deem it appropriate, newsworthy. I know of similar work being done by a fellow researcher of yours at U of MD, Erik de Leeuw, showing considerable promise as well.

Thanks again. Would love to know your thoughts on the potential of HDP-Mimics esp given its MOA, bacterial resistance less likely to develop.

Best regards,

More info below.
http://cellceutix.com/brilacidin/
http://files.shareholder.com/downloads/ABEA-4ITCYZ/0x0x598955/c3e5a236-e44a-4e85-80c8-25fe7733ec65/Host_Defense_Antimicrobial_Peptides.pdf
http://cellceutix.com/gram-negative-bacteria/#sthash.qPhhhkAi.dpbs