Isotechnika announces positive 12 month data from PROMISE trial



    EDMONTON, April 21 /CNW/ - Isotechnika Inc. (TSX:ISA) today announced
positive 12 month follow up data from the Phase 2b PROMISE trial evaluating
its lead drug, voclosporin, a next generation calcineurin inhibitor, in de
novo kidney transplant patients. As a dose ranging study, the Phase 2b trial
was successful in meeting the primary endpoint demonstrating non-inferiority
in biopsy proven acute rejection (BPAR) episodes as compared to tacrolimus
control in all three dose groups at six months. The extended data demonstrates
that voclosporin maintained efficacy at 12 months. Voclosporin also
demonstrated an improved safety profile versus tacrolimus. This trial was
designed to determine the most appropriate dosing strategy for the Phase 3
development programs of voclosporin in kidney transplantation. The extension
study provides sufficient data to implement a dosing strategy for Phase 3
designed to provide a better safety profile than tacrolimus while maintaining
efficacy at 12 months.
    Isotechnika is in ongoing discussions with regulatory agencies and
potential partners with regards to the planning and implementation of a Phase
3 pivotal trial for voclosporin in kidney transplantation. Physician
prescribing practices for transplant patients continue to be heavily
influenced by side effect profiles and market research indicates that three
significant side effect considerations are renal function, new onset diabetes
mellitus after transplant (NODAT) and neurological symptoms. Voclosporin in
its anticipated therapeutic range demonstrated less NODAT and neurological
symptoms with equivalent renal function. In addition, the pharmacokinetic and
pharmacodynamic analysis confirms a strong concentration-effect relationship
for voclosporin. Based on these results, the ideal dose for a Phase 3 trial
will encompass the concentration range obtained in the low to mid dose
treatment groups.
    "The results from this study are promising and demonstrate the potential
to decrease cases of new onset diabetes," stated Dr. Herwig-Ulf
Meier-Kriesche, Professor of Medicine, Medical Director Kidney Pancreas
Transplant Program, Central Florida Kidney Center Endowed Chair in Medicine,
University of Florida. "New onset of diabetes is really the Achilles heal of
most currently used immunosuppressive regimens for transplantation. A
calcineurin inhibitor which has the potential to achieve the same excellent
rejection prophylaxis and renal function preservation as tacrolimus with a
significant reduction in diabetogenicity while maintaining the impressive
safety profile of the calcineurin inhibitor family would mean significant
progress for our field."
    "I'm very pleased that our PROMISE study further demonstrated that the
efficacy of voclosporin is competitive with the market leader tacrolimus, with
the bonus of a favorable safety profile," stated Dr. Robert Foster,
Isotechnika's President & CEO. "This data combined with the previously
announced positive trial results in uveitis from our partner, Lux Biosciences,
adds further credibility to the commercial potential of voclosporin. Our next
steps are to confirm our Phase 3 transplant protocol with the FDA. As
previously outlined, Isotechnika continues to explore strategic partnerships
and/or licensing arrangements as a means to build value in our program and
fund the continued development of our product."

    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
or 0.8 mg/kg of voclosporin twice daily or a standard dose of tacrolimus. All
four arms of the study were then dosed to achieve trough blood concentration
levels as dictated by the protocol. A total of 41 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 de novo
kidney transplant patients receiving voclosporin for six months as compared to
tacrolimus control. Secondary endpoints examined clinical and laboratory
parameters such as kidney function, NODAT, electrolytes, neurological effects
and lipid parameters.

    Efficacy Results:

    BPAR is a measure of acute rejection in transplant. As a dose ranging
study, the Phase 2b trial was successful in meeting the primary endpoint
demonstrating non-inferiority in BPAR episodes as compared to tacrolimus
control in all three dose groups at six months. As specified by the protocol,
after six months, only the mid and high dose groups received a dose reduction
as is often standard practice with this class of drugs.

    
    -------------------------------------------------------------------------
                              Patients with BPAR        Patients with BPAR
    Drug                         at 6 months         between 6 and 12 months
    -------------------------------------------------------------------------
    Low dose voclosporin             11%                        2%
    -------------------------------------------------------------------------
    Mid dose voclosporin              9%                        8%
    -------------------------------------------------------------------------
    High dose voclosporin             2%                        3%
    -------------------------------------------------------------------------
    Tacrolimus                        6%                        0%
    -------------------------------------------------------------------------
    

    Data from a multicenter trial reported in 2008, suggest that rejection
rates in patients on tacrolimus after one year are in the range of 16-23%.
This indicates that the BPAR rates observed in all dose groups of voclosporin
fall within the expected range.

    Safety Results:

    The safety profile of voclosporin compared to tacrolimus was evaluated
again at 12 months by multiple assessments including renal function, NODAT,
hypertension and hyperlipidemia. Based on these assessments no specific safety
concerns were raised.

    Renal Function

    At 12 months, kidney function was well preserved in each of the three
dose levels of voclosporin relative to tacrolimus. Based on Nankivell
glomerular filtration rate (GFR) there were no statistical differences between
any of the voclosporin dose groups and tacrolimus. A statistical difference
was observed with iothalamate GFR in the high dose voclosporin group when
compared to tacrolimus (53 versus 62 mL/min) which is not unexpected as this
was a dose range finding study.

    
    -------------------------------------------------------------------------
                                          Nankivell GFR (mL/min)
    -------------------------------------------------------------------------
    Drug                     6 Month Results           12 Month Results
    -------------------------------------------------------------------------
    Low dose voclosporin              71                        70
    -------------------------------------------------------------------------
    Mid dose voclosporin              72                        72
    -------------------------------------------------------------------------
    High dose voclosporin             68                        69
    -------------------------------------------------------------------------
    Tacrolimus                        69                        73
    -------------------------------------------------------------------------
    

    The results suggest that over a wide range of dosing, there are minimal
changes in renal function.

    New Onset Diabetes Mellitus After Transplant (NODAT)

    NODAT is a serious complication in transplant patients and negatively
impacts patient outcomes. Published literature shows that mean graft survival
of 11 years decreases to eight years with NODAT. At 12 months there was a
meaningful reduction in NODAT in the low dose group of 81% as compared to
tacrolimus. Although not statistically significant, the mid dose group had a
clinically meaningful lower incidence of NODAT with a 66% reduction in risk.

    
    -------------------------------------------------------------------------
                                        Patients with NODAT
    -------------------------------------------------------------------------
    Drug                     6 Month Results           12 Month Results
    -------------------------------------------------------------------------
    Low dose voclosporin            1.6%                      3.2%
    -------------------------------------------------------------------------
    Mid dose voclosporin            5.7%                      5.7%
    -------------------------------------------------------------------------
    High dose voclosporin          17.7%                     21.0%
    -------------------------------------------------------------------------
    Tacrolimus                     16.4%                     16.4%
    -------------------------------------------------------------------------
    

    Hypertension

    Systolic blood pressure was statistically significantly higher in
voclosporin treated patients compared to tacrolimus treated patients, however
there was no difference in the number of patients treated for hypertension.
The absolute difference ranged from a 5 to 8 mmHg increase, and no dose
dependency was seen. No statistical differences were noted in diastolic blood
pressure.

    Neurological Events

    Voclosporin has consistently shown a lower proportion of patients
experiencing insomnia and tremors at both six and 12 months as compared to
tacrolimus.

    
    -------------------------------------------------------------------------
                                     Tremors                  Insomnia
    -------------------------------------------------------------------------
    Drug                      6 Months    12 Months    6 Months    12 Months
    -------------------------------------------------------------------------
    Low dose voclosporin        11.9%        13.1%        7.1%         7.1%
    -------------------------------------------------------------------------
    Mid dose voclosporin        22.1%        23.4%       10.4%        10.4%
    -------------------------------------------------------------------------
    High dose voclosporin       13.8%        13.8%        8.0%         6.8%
    -------------------------------------------------------------------------
    Tacrolimus                  22.1%        24.4%       14.0%        15.1%
    -------------------------------------------------------------------------
    

    About Isotechnika

    Edmonton-based Isotechnika Inc. is a 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 have been completed and data is being collected and analyzed.
Our partner, Lux BioSciences, Inc., has recently completed three separate
Phase 2/3 pivotal trials investigating voclosporin (referred to as LUVENIQ(TM)
by Lux) for the treatment of uveitis. In addition to the uveitis trials, Lux
BioSciences Inc. has also commenced a Phase 1 trial using their proprietary
voclosporin ophthalmic solution (LX214) as a candidate for dry eye syndrome.
Voclosporin has also entered 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 or www.SEDAR.com.

    
    Forward-Looking Statements
    --------------------------
    
    This press release may contain 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, the
availability of funds and resources to pursue research and development
projects, 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, 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. Investors should consult the
Company's quarterly and annual filings with the Canadian commissions for
additional information on risks and uncertainties relating to the forward-
looking statements. Investors are cautioned against placing undue reliance on
forward-looking statements.

    %SEDAR: 00010508E




For further information:

For further information: Dr. Robert Foster, President & CEO, Isotechnika
Inc., Phone: (780) 487-1600 Ext. 247, Fax: (780) 484-4105, Email:
rfoster@isotechnika.com

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ISOTECHNIKA PHARMA INC.

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