Isotechnika presents positive data from the promise trial of voclosporin at the American Transplant Congress



    EDMONTON, June 4 /CNW/ - Isotechnika Inc. today announces the successful
results of the Phase 2b PROMISE trial which were presented by Dr. A. Osama
Gaber, an investigator for the PROMISE trial, at the 2008 American Transplant
Congress in Toronto, Canada. The presentation detailed the final data
confirming the efficacy of Isotechnika's next generation calcineurin
inhibitor, voclosporin (ISA247), in de novo kidney transplant patients. An
improved safety profile versus tacrolimus was also reported. Dr. Gaber is the
Director of Transplantation, Vice-Chair for Administration and Faculty
Affairs, Department of Surgery, The Methodist Hospital (Houston) and Cornell
University (New York).
    "Despite the advances in transplant medicine which have allowed patients
to lead healthier, more fulfilling lives, there is still an unmet medical need
in these patients, and room for improvement in the drug regimens used to
preserve organ function," stated Dr. Gaber. "In this study, voclosporin
demonstrated encouraging results with regards to both efficacy and safety
parameters, specifically new onset diabetes mellitus."

    Calcineurin Inhibitor Market

    Tacrolimus is the global market leader in transplant, garnering about 75%
of the US calcineurin inhibitor market. Calcineurin inhibitors are a core part
of the drug regimen of kidney transplant patients, 93% of whom receive a
calcineurin inhibitor. Worldwide, the calcineurin inhibitor market is
currently approximately $2.8 billion, and expected to grow to $4 billion by
2010.

    Efficacy

    In PROMISE, the primary endpoint (biopsy proven acute rejection, BPAR)
was clearly met in all three voclosporin dose groups. BPAR is a measure of
acute rejection in transplant. In clinical practice, patients with more
episodes of BPAR, typically 10-15% at 6 months, have worse outcomes. The
results show that voclosporin is as efficacious as tacrolimus, has the dose
response expected in a Phase 2 trial, and provides the rationale for dose
selection for the Phase 3 clinical program.

    
    -------------------------------------------------------------------------
    Drug                                                  Patients with BPAR
    -------------------------------------------------------------------------
    Low dose voclosporin                                               11%(*)
    -------------------------------------------------------------------------
    Mid dose voclosporin                                                9%(*)
    -------------------------------------------------------------------------
    High dose voclosporin                                               2%(*)
    -------------------------------------------------------------------------
    Tacrolimus                                                          6%
    -------------------------------------------------------------------------
    (*)statistically non-inferior to tacrolimus
    

    Safety

    The three dose groups of voclosporin were shown to be safe. Voclosporin
demonstrated improvements over tacrolimus in several key areas, specifically
with respect to NODM, triglycerides, magnesium, insomnia and tremors.

    New Onset Diabetes Mellitus (NODM)
    NODM is a serious complication in transplant patients and negatively
impacts patient outcomes. Published literature shows that mean graft survival
of 11 years decreases to 8 years with NODM.
    A statistically significant lower incidence of NODM was seen in the low
dose voclosporin group, translating into a 90% reduced risk of developing NODM
as compared to tacrolimus. Although not statistically significant, the mid
dose group had a clinically meaningful lower incidence of NODM with a 65%
reduced risk. The high dose group had an incidence of NODM that was not
clinically different than tacrolimus. This reduced burden of NODM in the low
and mid dose groups represents a large benefit to patients.

    Triglycerides
    Triglyceride elevation is risk factor of cardiovascular complications.
The low dose voclosporin group showed a statistically significant reduction in
the number of incidences of elevated triglycerides compared to tacrolimus
translating into a 55% risk reduction. The mid and high dose groups showed a
24 to 30% reduced risk of elevated triglycerides.

    Magnesium
    Magnesium is involved in many important functions in the body, and is
regulated by the kidneys. Low magnesium levels can lead to cardiac arrhythmia,
hypertension, muscle cramps, and increased irritability of the nervous system,
resulting in tremors, confusion, hallucinations and insomnia. Voclosporin
showed significantly higher levels of magnesium than tacrolimus, improving the
overall safety profile.

    
    -------------------------------------------------------------------------
                                     Patients      Elevated      Magnesium
    Drug                            with NODM    Triglycerides   (6 months)
    -------------------------------------------------------------------------
    Tacrolimus                        16.4%           39.2%     1.77 mmol
    -------------------------------------------------------------------------
    Low dose voclosporin               1.6%(*)        17.5%(*)  1.98 mmol(xx)
    -------------------------------------------------------------------------
    Mid dose voclosporin               5.7%           29.7%     1.95 mmol(xx)
    -------------------------------------------------------------------------
    High dose voclosporin             17.7%           27.5%     1.89 mmol(xx)
    -------------------------------------------------------------------------
    (*)  Significantly different from tacrolimus, p(less than)0.05
    (xx) Significantly different from tacrolimus, p(less than)0.005
    

    Voclosporin also showed trends to a reduced incidence of insomnia and
tremors at the six month time point as compared to tacrolimus. This reduced
side effect burden is also clinically meaningful to patients and their
physicians.

    
    -------------------------------------------------------------------------
                                                     Tremors
    Drug                                           (6 months)      Insomnia
    -------------------------------------------------------------------------
    Tacrolimus                                        12.5%          14.0%
    -------------------------------------------------------------------------
    Low dose voclosporin                               3.0%           7.1%
    -------------------------------------------------------------------------
    Mid dose voclosporin                               3.1%          10.4%
    -------------------------------------------------------------------------
    High dose voclosporin                              2.9%           6.9%
    -------------------------------------------------------------------------
    

    Kidney Function
    In the evaluation of kidney function, there were no significant
differences noted between the voclosporin and tacrolimus groups. Kidney
function was well preserved in each of the three dose levels of voclosporin
relative to tacrolimus. Voclosporin did not meet one of the secondary
objectives, a 5% improvement in kidney function as determined by iothalamate
GFR.

    
    -------------------------------------------------------------------------
                                   Iothalamate     Nankivell        Serum
                                       GFR            GFR        Creatinine
    Drug                             (mL/min)       (mL/min)   ((micro)mol/L)
    -------------------------------------------------------------------------
    Tacrolimus                           65             69            120
    -------------------------------------------------------------------------
    Low dose voclosporin                 56             71            122
    -------------------------------------------------------------------------
    Mid dose voclosporin                 64             72            123
    -------------------------------------------------------------------------
    High dose voclosporin                60             68            131
    -------------------------------------------------------------------------
    Better kidney function is indicated by a higher GFR and a lower serum
    creatinine.
    

    The results indicate that the dosage can be adjusted to maximize efficacy
without having deleterious effects on the kidney.

    Dose response relationship

    Analysis of the pharmacokinetic and pharmacodynamic data from this trial
suggests that an ideal dosing strategy is readily identifiable with
voclosporin. A wide therapeutic window which optimizes both efficacy and
safety has now been confirmed, allowing transplant physicians and surgeons to
individualize voclosporin dosing for their patients.
    "These positive results clearly demonstrate that voclosporin offers
significant clinical benefit. We believe that the efficacy and enhanced safety
profile of voclosporin compared to the market leader tacrolimus gives us a
product that offers significant benefit to patients. These attributes also
confirm voclosporin's commercial potential in a market which is predicted to
grow to more than $4 billion by 2010," stated Dr. Robert Foster, Chairman and
CEO of Isotechnika Inc. "We look forward to advancing voclosporin into pivotal
phase 3 trials and moving one step closer to commercialization."

    Phase 2b Trial Design

    PROMISE is a randomized, multicenter, open-label, concentration
controlled, dose ranging, safety study of voclosporin and tacrolimus in de
novo renal transplant patients. Patients received an initial dose of 0.4, 0.6
and 0.8 mg/kg twice daily. All four arms of the study were dosed to trough
blood concentration levels as dictated by the protocol. A total of 42 centers
participated in the study, and 334 patients were enrolled. The primary
endpoint was defined as non-inferiority in biopsy proven acute rejection
(BPAR) episodes in patients receiving voclosporin for six months as compared
to tacrolimus control. Secondary endpoints examined clinical and laboratory
parameters such as kidney function, electrolytes, neurological effects, NODM
and lipid parameters.

    About Isotechnika
    -----------------
    Edmonton-based Isotechnika Inc. is an international biopharmaceutical
company focused on the discovery and development of novel immunosuppressive
therapeutics that are designed to offer advantages over other currently
available treatments. There is a significant unmet medical need in the
treatment of both solid organ transplantation and autoimmune disease. It is
estimated that the market potential will exceed $4 billion annually in sales
for calcineurin inhibitors such as voclosporin by 2010.
    Voclosporin is a next generation calcineurin inhibitor, which recently
completed a Phase 2b North American trial for the prevention of kidney
rejection following transplantation. An extension to the Phase 2b trial and a
combined Phase 3 European/Canadian trial for the treatment of moderate to
severe psoriasis are ongoing. Our partner, Lux Biosciences, is currently
conducting three separate Phase 2/3 pivotal trials investigating voclosporin
(referred to as LX211 by Lux) for the treatment of uveitis. Voclosporin has
also been approved to enter First-in-Man trials as the drug utilized in the
CINATRA(TM) Drug Coated Coronary Stent system developed by the Company's
partner, Atrium Medical Corporation.
    Isotechnika Inc. is a publicly traded company on the Toronto Stock
Exchange under the symbol "ISA". More information on Isotechnika can be found
at www.isotechnika.com.

    Forward-Looking Statements
    --------------------------
    This press release may contain forward-looking statements. Such
forward-looking statements involve known and unknown risks, uncertainties and
other factors that may cause actual results, events or developments to be
materially different from any future results, events or developments expressed
or implied by such forward-looking statements. Forward-looking statements,
including the Company's belief as to the potential of its products, the
Company's expectations regarding the issuance of additional patents and the
Company's ability to protect its intellectual property, involve known and
unknown risks and uncertainties, which could cause the Company's actual
results to differ materially from those in the forward-looking statements.
Such risks and uncertainties include, among others, securing and maintaining
corporate alliances, the need for additional capital and the effect of capital
market conditions and other factors on capital availability, the ability to
economically manufacture its products, the potential of its products, the
success and timely completion of clinical studies and trials, the Company's
ability to successfully commercialize its products, competition, the ability
of the Company to defend its patents from infringement by third parties, and
the risk that the Company's patents may be subsequently shown to be invalid or
infringe the patents of others. Additional risks and uncertainties relating to
the Company and its business can be found in the "Risk Factors" section of the
Company's Annual Information Form. These factors should be considered
carefully and readers are cautioned not to place undue reliance on such
forward-looking statements.

    %SEDAR: 00010508E




For further information:

For further information: Dr. Robert Foster, Chairman & CEO, Isotechnika
Inc., Phone: (780) 487-1600 Ext. 272, Fax: (780) 484-4105, Email:
rfoster@isotechnika.com; Stephanie Gillis-Paulgaard, Director, Corporate
Communications, Isotechnika Inc., Phone: (780) 909-4661, Email:
sgillis-paulgaard@isotechnika.com

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ISOTECHNIKA PHARMA INC.

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