Positive Phase 3 uveitis trial results for voclosporin reported by Isotechnika's partner Lux Biosciences
EDMONTON, March 26 /CNW/ - (ISA:TSX): Isotechnika Inc. today announced that their partner, Lux Biosciences, Inc., reported the results from the three Phase 3 LUMINATE trials investigating voclosporin oral capsule (LUVENIQ(TM) or LX211) for the treatment of uveitis. Voclosporin is a next generation calcineurin inhibitor that Isotechnika has licensed to Lux for ophthalmic indications. The data show a positive effect on ocular inflammation and a safety profile consistent with the expected use in uveitis. Following full analysis of the data, the results of the LUMINATE clinical trials will be submitted for publication and presented at upcoming conferences. In parallel, Lux Biosciences will be preparing submissions for approval.
"The available results from the LUMINATE program demonstrate that LUVENIQ, if approved, can play a significant role in the treatment of inflammation in certain forms of sight-threatening uveitis," said Eddy Anglade, M.D., Lux Biosciences' Chief Medical Officer. "A significant unmet therapeutic need exists for an approved agent which is not a corticosteroid and allows sparing of those drugs to reduce their associated, serious side effects."
"These results further demonstrate the ability of voclosporin to impact a wide range of autoimmune conditions and highlight its broad commercial potential," said Dr. Robert Foster, President and Chief Executive Officer of Isotechnika. "We are committed to support Lux as they move forward with their LUVENIQ filings."
The three randomized, double-masked, dose-ranging and placebo-controlled trials comprising the LUMINATE Program, the largest clinical program ever conducted in uveitis, enrolled 558 patients in 7 countries (United States, Canada, United Kingdom, France, Germany, Austria and India). The key results in the LUMINATE trials were:
- Overall, of the 3 doses studied, the 0.4 mg/kg BID dose had the most
acceptable safety profile relative to effect on the disease.
Isotechnika, Inc. previously reported that 0.4 mg/kg BID demonstrated
both efficacy and an acceptable safety profile in their clinical
trial of voclosporin in plaque psoriasis, which is in the range of
the maintenance dose of voclosporin anticipated for use in kidney
- Study LX211-01 enrolled 218 patients with active non-infectious
uveitis with posterior manifestation of the disease. The 0.4 mg/kg
BID dose fully met the primary endpoint of superiority to placebo at
both weeks 16 (p=0.008) and week 24 (p=0.04)
for mean change from baseline in vitreous haze, a validated measure
of inflammation of the posterior segment of the eye. The magnitude of
the effect was (greater than)1 step change, demonstrating a
clinically relevant benefit.
- Study LX211-02 enrolled 232 patients with clinically quiescent
disease. The 0.4 mg/kg BID dose showed a reduction by 50% vs. placebo
in rate of recurrence of inflammation at 6 months. The study did not
meet the primary analysis endpoint of all-cause therapeutic failure
at 6 months as the drug effect on inflammation was diluted by
discontinuations that were unrelated to inflammation. This was due to
a pre-specified analysis that accounted for data censoring due to
non-efficacy-related discontinuations. However, the reduction in
inflammation vs. placebo by 50% was statistically significant
(p=0.046), thus confirming the positive results from
- Study LX211-03 enrolled a narrow sub-set of 108 patients with active
uveitis with anterior manifestation of the disease. The efficacy of
the voclosporin dose groups and placebo did not separate during the
steroid taper; all showed an improvement by (greater than)1 step mean
reduction from baseline in anterior chamber cells, a validated
measure of inflammation in the anterior segment of the eye. This
study, which is not critical for approval and was added to encompass
a sub-set of patients affected by anterior chamber disease, turned
out to be underpowered owing to greater than expected variability.
The integrated safety profile of 0.4 mg/kg BID voclosporin in the LUMINATE trials suggests that it would be suitable for chronic use in this high medical need indication. Of particular interest were the relatively small effects of voclosporin 0.4 mg/kg BID on renal function, an area of concern for first generation calcineurin inhibitors. The proportion of subjects experiencing a confirmed rate of decrease in estimated glomerular filtration rate (eGFR) by (greater than or equal to)30% was 8.2% in the 0.4 mg/kg BID dose group vs. 2.7% in the placebo group. Patients experienced a mean increase in systolic blood pressure by study-end over baseline of 6 mm Hg. However, most of these patients were successfully controlled with medication and only 1.3% discontinued therapy due to hypertension. Other adverse events typical of the calcineurin inhibitor class, in particular diabetes, elevation of lipids, hypomagnesemia, and tremor, were not observed in the LUMINATE studies. Other more frequently observed adverse events included headache, diarrhea and infections, which were similar in incidence to placebo. In terms of ocular safety there was no apparent effect on intraocular pressure, cataract formation or endothelial cell density.
Ulrich Grau, Ph.D., Lux Biosciences' President and Chief Executive Officer, said, "Based on the available data from the LUMINATE pivotal trial program, we plan to engage in discussions with several regulatory agencies and plan regulatory filings of LUVENIQ in the near future. We are gratified by what appears to be a robust clinical effect of LUVENIQ coupled with an acceptable side effect profile."
Voclosporin is designed for use as an oral immune-modulatory agent to treat the forms of non-infectious uveitis that require systemic treatment, including posterior, intermediate and panuveitis, allowing for tapering of systemic corticosteroids to 5 mg or less per day. The mean age of these patients is approximately 40 years and uveitis is the 4th leading cause of blindness; hence, the burden of disease is relatively higher than for age-related ophthalmic diseases, and the medical need for effective treatments is striking. If approved for commercialization by regulatory agencies, voclosporin would be the first corticosteroid-sparing agent available in the United States and most other markets for the treatment of uveitis.
Uveitis is an autoimmune disease characterized by chronic inflammation of the eye. Uveitis is an under-diagnosed and under-recognized medical condition that causes vision impairment, ocular pain, and loss of vision. Experts estimate that 10% of new cases of blindness in the United States result from this disease. Approximately 300,000 people suffer from uveitis in the United States alone. The only therapeutic class approved by the FDA for treatment of uveitis is corticosteroids, which are burdened with multiple side effects, such as osteoporosis, hyperglycemia, hypercholesterolemia, hypertension, mood disturbances, and if applied chronically to the eye, cataract formation and glaucoma.
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 have been completed and data is being collected and analyzed. Our partner, Lux Biosciences, 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 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.
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 -30- /For further information: Dr. Robert Foster, President & CEO, Isotechnika Inc., Phone: (780) 487-1600, Fax: (780) 484-4105, E-mail: email@example.com/
Posted: March 2009