Replies to post #212080 on Innovation Pharmaceuticals Inc (IPIX)

[WILD_4_IPIX]

YOU ROCK PLENTY !Thanks for all your efforts to stop the avalanche of Bullshit ! Much appreciated !

GO IPIX !

[To infinity and beyond!]

first of all I love the whiny chair attack

will have some time in a next 2 days to be sure your numbers are right

if so easy to estimate then why not reported by IP? Still does not add up to me but I am more than happy to be proven to be just plain lazy

will get back to you

[georgejjl]

Absolute proof that AF's intent was and is to distort the truth

Quote:
That single serious adverse event was actually a serious increase in liver enzymes (a sign of liver toxicity) in a patient treated with the 50 mg dose of Prurisol, according to the data presented by the company on Sept. 19.

Additional patients treated with the higher doses of Prurisol also reported increases in liver enzymes, some greater than two times the upper limit of normal, according to the Sept. 19 presentation of the Phase 2 study results.

Cellceutix has not told investors about the Prurisol-related liver toxicity seen in its Phase II study. This is especially concerning because the company is using higher Prurisol doses (300 mg and 400 mg) in its next Phase 2 study. Prurisol is a prodrug of abacavir, an old HIV drug known to cause serious hypersensitivity reactions in some patients.


https://www.thestreet.com/story/13960573/2/biotech-school-when-cellceutix-ceo-rants-about-criminal-short-smart-investors-see-red-flags.html

AF said:

Quote:
That single serious adverse event was actually a serious increase in liver enzymes (a sign of liver toxicity) in a patient treated with the 50 mg dose of Prurisol, according to the data presented by the company on Sept. 19.

Additional patients treated with the higher doses of Prurisol also reported increases in liver enzymes, some greater than two times the upper limit of normal, according to the Sept. 19 presentation of the Phase 2 study results.


**********************************************************************

So let's look at the competition that is already approved by the FDA to treat psoriasis.

Celgene's Otezla (apremilast)

Quote:
ALT and AST abnormalities (3-fold increases over the upper limit of normal) were observed in numerically more apremilast patients than placebo patients in clinical trials


http://www.pbm.va.gov/PBM/clinicalguidance/criteriaforuse/Apremilast_(OTEZLA)_Criteria_for_Use_in_Psoriasis_and_Psoriatic_Arthritis.pdf

Abbvie's Humira (adalimumab)

Quote:
sixteen patients (nine treated with adalimumab and seven treated with placebo) developed AST and ALT liver enzyme elevations greater than twice the ULN. Overall between one and four percent of adalimumab-treated patients developed > 2 fold elevation of liver enzymes.


http://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/ucm092768.pdf

Janssen Biotech, Inc (Johnson & Johnson's) Remicade (infliximab)

Quote:
Infliximab has been associated with at least four forms of hepatic injury which have quite separate causes and different clinical outcomes. First, infliximab can cause serum aminotransferase elevations, which generally arise after 2 to 5 infusions....

A second type of liver injury associated with infliximab use is a hepatocellular injury typically associated with autoimmune markers. Infliximab induces autoantibodies including antinuclear (ANA), smooth muscle (SMA) and double-stranded DNA autoantibodies (anti-dsDNA), in a high proportion of patients....

A third form of Infliximab induced liver injury is a cholestatic form of liver injury that can arise as early as a few days to up to 24 weeks after starting therapy. Symptoms include jaundice and pruritus, and liver biopsy shows cholestasis with mild inflammation....

A fourth type of hepatic injury caused by infliximab is reactivation of chronic hepatitis B (Case 3). Patients receiving infliximab for an autoimmune condition who are also HBsAg carriers can have a reactivation of hepatitis B virus (HBV) activity with rise in serum HBV DNA concentrations, followed by abnormal ALT levels and clinically apparent hepatitis with jaundice. Reactivation of hepatitis B can be severe and the mortality rate among jaundiced cases is at least 10%. The rise in HBV DNA levels usually occurs within the first few months of infliximab therapy, but is clinically silent until after ALT levels rise 2 to 6 months later.


https://livertox.nlm.nih.gov/Infliximab.htm

Novartis's Cosentyx (secukinumab)

Quote:
For liver function parameters in Pool A, the incidence of liver enzyme elevations was generally low and comparable among treatment groups. While a numerically higher proportion ofelevations in ALT or AST >5×ULN was noted with 150 mg secukinumab vs. placebo, there was no dose response for secukinumab and rates were comparable to etanercept (0.3%, 0.9%, 0.3%, and 0.9%, respectively, for 300 mg, 150 mg, placebo, and etanercept). Combined elevations in ALT or AST >3×ULN and TBL >2×ULN in Pool A were observed in 1 (0.1%) patient on 150 mg secukinumab and 1 (0.1%) placebo patient.


http://www.fda.gov/downloads/AdvisoryCommittees/UCM419023.pdf

Amgen's Enbrel (etanercept)

Quote:
Etanercept has been associated with low rates of serum ALT elevations during therapy that are generally asymptomatic, transient, and do not require dose modifications. There have been isolated reports of clinically apparent liver injury during etanercept therapy, but the frequency has been far less than with infliximab, and several patients with infliximab induced liver injury have been reported to tolerate etanercept without recurrence. Etanercept therapy can be associated with induction of autoantibodies, including antinuclear antibody (ANA) and cases of autoimmune hepatitis, induced or exacerbated by etanercept therapy have been reported. The latency to onset has ranged greatly, from as short as 2 weeks to as long as several years. The pattern of serum enzyme elevations has also varied, both cholestatic and hepatocellular injury being reported. Immunoallergic manifestations such as fever, rash and eosinophilia are rare. Autoimmune phenomena are reported and the injury is reportedly responsive to corticosteroid therapy. How frequently the disease recurs after corticosteroids are discontinued has not been carefully assessed.

Etanercept has been linked to rare cases of reactivation of hepatitis B, although less frequently than infliximab. Reactivation typically occurs in patients who are inactive HBsAg carriers, with normal serum aminotransferase levels and no or only low levels of HBV DNA in serum. The immune suppression caused by the immunomodulatory agent leads to an increase in HBV replication and rise in serum HBV DNA levels. With stopping immune suppression (or between cycles of therapy), restoration of immune function leads to an acute immunological response to the heightened viral replication and a flare of hepatitis, that can be severe and can result in hepatic failure and death. Reactivation in patients with anti-HBc without HBsAg (serologic pattern of previous HBV infection) has not been reported in patients treated with etanercept, but has been reported after therapy with other TNFa antagonists and more commonly with rituximab and after bone marrow transplantation. The anti-TNF inhibitors have little or no effect on hepatitis C virus levels and have been used safely in patients with chronic hepatitis C.


https://livertox.nlm.nih.gov/Etanercept.htm

I could go on but that is more than sufficient to say that elevated liver enzyme levels is not an issue unique to or problematic for Cellceutix's Prurisol. QED

Good luck and GOD bless,

George

[DaubersUP]

Really good post. The market will understand when its printed and confirmed in the phase 2b data. Peeps like Infiniti need apple to apple tests to understand.

He shall have it

[kfcyahoo]

PP,

I'm beginning to wonder if, perhaps, Leo should audition for Shark Tqnk. Never watched the show until this past Sunday night when our son advised us that he had just received a text from a friend telling him to tune in because his friend's brother was going to be on the show. Ten minutes later(after the presentation), Mark Cuban offered $200,000 down and a 23% royalty on sales.

Ten minutes- done(I'm sure there was plenty more leg work to get there). Point being, there's money out there. The winner of the above noted show has just turned 20 years old and this his second major venture(he's also a college student).

[LilyGDog]

IPIX is amazing... Great post and thanks for taking the time to do this.

Well, Infinity, actually they did tell us something.

I just takes an effort to lift ones mental ass off from the whiny chair and do something called estimating. Lemme show you how:

We know that there were 6 subjects (0.462 * 13 = 6) in prurisol 200 mg group with IGA 3 that had 2 point drop. Numbers for 200 mg ITT group were 28 subjects and 18 of them were IGA 3. Let's be stingy and assume that the seventh 2 point drop in ITT did not happen in IGA 3 group. We get:

prurisol 200 mg ITT IGA 3 - 2 point change percentage: 100*6 /18 = 33.3 % (at least)

Placebo group had ITT of 30 out which 23 was IGA 3. This group had 4 subjects with 2 point IGA drop. Let's be generous and assume that all four happened in IGA 3 subjects. That means

placebo ITT IGA 3 - 2 point change percentage: 100*4/23 = 17.4 % (at most)

Risk ratio associated with 2 point drop in IGA 3 groups: 0.52 for prurisol (and probably better). A number that is known to imply clear statistical significance in 100+ subjects trials.

BTW:In Esteem 2 trial Otezla scored PASI 75 percentage of 28.8 % when calculated using LOCF. Prurisols results in p2a are probably better than that. Strange: It looks like Leo did not lie, but famous Adam F. might have. Who would have thunk THAT!

[BooDog]

Nice work PP. $IPIX will be making their mark and leave a few chasing. I know I have the patience, and thankful to be able to continue accumulating.

Brilacidin results good enough to go ahead and start the preps for meeting with the FDA, kevetrin with its modulation and expressions and though some are on the fence about prurisol, it's my opinion it has much better than a 50% chance of moving forward. Across the pipeline, looking very good imo. Mr. Market can wait for final data and partnerships, I won't be chasing.

[To infinity and beyond!]

had a minute to look at numbers, which are oddly confusing

what do I mean by that: back to the green line on the sept presentation, page 12: they say initial IGA 3 was 68 and 32 % for 200 mg group, so real numbers are 19 of 28. At close of trial 25% remain IGA 3- so is that 7 of 28? But there were dropouts and totals do not add to 100% at conclusion but 86%

And that would suggest that 12 of 28 or 43% responded with IGA change >/= 2. And yet they prev said 7 of 27 responded

However, and nonetheless: Forgetting this odd stuff, and using the numbers you provided.

The stingy and the generous categories are the right approach but the very simple fact is that you are willing to make one of the same mistakes as IP in presenting the data- which is that very small numbers do NOT justify use of percentages and enable NO confidence.

The difference between 6 responders and 4 responders is just not significant, and it is nothing to hang your hat on.
yes it enables them to move the trial forward. No it does not inspire any confidence

But you are right that you can make some educated guesses about the placebo group if you just try a little bit, and there I am guilty of whining, as you point out.

The larger issues, though, are that (1) IP should make this info transparent, and (2) the numbers are too small to be very useful