Lux Biosciences, Inc. today announced its submission of simultaneous regulatory filings to both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking marketing approval for its investigational drug LUVENIQ™ (LX211; oral voclosporin) for the treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye. Efficacy of LX211 in support of the indication sought was demonstrated in two controlled, randomized, multi-center trials including data from 450 patients at 56 sites in 7 countries. The safety data include a total of 2,110 subjects who received voclosporin during its clinical development in uveitis and psoriasis, about 500 of whom were treated for >36 weeks and about 200 for >52 weeks. LX211 had previously received orphan drug status from FDA and EMA, and fast track status from FDA. Based on the latter, Lux Biosciences has requested priority review from FDA.
“The results seen in the LUMINATE clinical trial program, the largest completed to date in non-infectious uveitis, support our belief that LX211 has the potential to significantly advance the treatment of this blinding disease,” said Ulrich Grau, Ph.D., Lux Biosciences’ President and Chief Executive Officer. “This is the first regulatory filing of voclosporin in any indication, in any country, which made this submission a complex task. It incorporates the research and development undertaken by our collaboration partner Isotechnika over more than a decade, and that of Lux Biosciences over the last 3 ?? years. Simultaneous filings of both a U.S. New Drug Application (NDA) and a European Marketing Authorization Application (MAA) for LX211 represent a major milestone for Lux Biosciences.”
He added, “I wish to thank all of the Lux Biosciences employees, our partner Isotechnika, investigators, patients, contractors and advisors who contributed to the development program and made these on-time filings possible. I am not aware of a company of our small size having accomplished a submission of this magnitude for a new molecular entity simultaneously in the United States and Europe. It is a tribute to our networked approach to development, whereby a large team led and managed by a small core group was able to complete a major international drug development program in record time.”
Results from the LUMINATE program, submitted in support of both the U.S. and European marketing applications, showed that LX211 at the recommended dose of 0.4 mg/kg twice daily provided clinically meaningful efficacy and enabled preservation of vision in treated patients, a critical patient benefit. Study LX211-01, in subjects with uncontrolled uveitis, showed LX211 to rapidly reduce inflammation in subjects with moderately severe disease, either alone or in combination with systemic corticosteroids. Subjects receiving LX211 experienced a 50% reduction in mean vitreous haze as compared to 29% in placebo-treated subjects. The proportion of subjects demonstrating an improvement of at least 2 grades in vitreous haze or a grade of ?��1+ for the study eye at last visit was 64% in the LX211 group as compared to 46% in the placebo group. Moreover, treatment with LX211 permitted the withdrawal of immunosuppressive therapy and the use of 5 mg/day or less of prednisone.
Study LX211-02 demonstrated the efficacy of LX211 in subjects whose disease was clinically quiescent at the time of enrollment. Nearly 90% of the patients in this study were receiving one or more forms of systemic immunosuppression prior to randomization. In this study, treatment with LX211 resulted in a 50% reduction in the rate of inflammatory exacerbations at the 26-week primary endpoint compared to those receiving placebo; a similar result was observed at 50 weeks. This indicates that relative to placebo, a patient’s exposure to ocular inflammatory exacerbations that lead to loss of vision and to potentially damaging exposure to high rescue doses of steroids is approximately cut in half when LX211 therapy is administered at the clinically effective dose. Treatment with LX211 also enabled the concomitant withdrawal of immunosuppressive therapy and allowed the reduction of systemic corticosteroids to 5 mg/day or less, as well as the complete elimination of topical corticosteroid therapy.
The most common adverse events (>5%) occurring at a rate higher in treated patients than those receiving placebo, regardless of whether they were drug related or not, were hypertension, decreased renal function, diarrhea, pyrexia and arthralgia. All cases of reported hypertension were treatable, and all cases of decreased renal function were reversible. The most commonly observed infections reported were nasopharyngitis, urinary tract infection, and upper respiratory infections, but no opportunistic infections were observed. Adverse event risks in general did not appear to be increased with longer-term use. Additionally, no meaningful signals of more serious treatment effects were observed, even at a lesser frequency, in either study.
“LX211 at the recommended dose of 0.4 mg/kg twice daily, possesses a favorable benefit-risk profile for the treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye,” said Eddy Anglade, M.D., Lux Biosciences Chief Medical Officer. “If approved, LX211 would offer physicians a valuable oral treatment option capable of modifying the course of uveitis by effectively controlling the inflammation that characterizes this potentially blinding eye disease and significantly reducing its rate of recurrence. Avoiding inflammatory exacerbations that result in ocular morbidity and the loss of vision, coupled with avoidance of steroid-induced morbidities, is central to the management of patients afflicted with uveitis. LX211 has been shown to provide a means to attain these therapeutic goals in a disease that requires effective intervention and for which current therapeutic options are limited and deficient.”
About LUVENIQ™
LUVENIQ (LX211) is the oral form of a next-generation calcineurin inhibitor, voclosporin. Like other molecules of this class, the compound reversibly inhibits immunocompetent lymphocytes, particularly T-lymphocytes, and it also inhibits lymphokine production and release. Lux Biosciences has exclusive worldwide rights to voclosporin for ophthalmic use and is cooperating with the team at Isotechnika Pharma who discovered the molecule and develop it in psoriasis and organ transplantation.
About Uveitis
Uveitis, which represents a group of serious inflammatory eye conditions, is inevitably associated with either severe vision loss or substantial morbidity from steroid use. Non-infectious uveitis involving the posterior segment of the eye is a leading cause of vision loss and long-term disability and the fourth leading cause of legal blindness in the industrialized world. As the majority of uveitis patients are first diagnosed at ages under 40 years, the socio-economic burden of this disease is higher than that of other serious ocular conditions such as AMD and diabetic macular edema.
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Lux Biosciences