Innovation Pharmaceuticals Inc (IPIX)

[georgejjl]

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

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:

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.

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

Celgene's Otezla (apremilast)

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)

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)

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)

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)

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