Isotechnika Presents Positive Data From the Promise Trial of Voclosporin at the American Transplant Congress
Edmonton, Canada (ots/PRNewswire)
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 CND$2.8 billion, and expected to grow to CND$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%(x)
Mid dose voclosporin 9%(x)
High dose voclosporin 2%(x)
Tacrolimus 6%
(x)statistically non-inferior to tacrolimusSafety
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%(x) 17.5%(x) 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)
(x) Significantly different from tacrolimus, p(less than)0.05
(xx) Significantly different from tacrolimus, p(less than)0.005Voclosporin 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 CND$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 CND$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 http://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.
For further information: Dr. Robert Foster, Chairman & CEO, Isotechnika Inc., Phone: +1-780-487-1600 Ext. 272, Fax: +1-780-484-4105, Email: rfoster@isotechnika.com; Stephanie Gillis-Paulgaard, Director, Corporate Communications, Isotechnika Inc., Phone: +1-780-909-4661, Email: sgillis-paulgaard@isotechnika.com
Contact:
For further information: Dr. Robert Foster, Chairman & CEO,
Isotechnika Inc., Phone: +1-780-487-1600 Ext. 272, Fax:
+1-780-484-4105, Email: rfoster@isotechnika.com; Stephanie
Gillis-Paulgaard, Director, Corporate Communications, Isotechnika
Inc., Phone: +1-780-909-4661, Email:
sgillis-paulgaard@isotechnika.com