Luveniq Advisory Committee: Renal Side Effects May Be Key Issue With Immunosuppressant

Lux Biosciences' Luveniq (voclosporin) for uveitis will undergo review by FDA's Dermatologic and Ophthalmic Drugs Advisory Committee on June 28.

Lux Biosciences' Luveniq (voclosporin) would be the first new treatment for uveitis since corticosteroids became the standard treatment in the 1960s, but renal and blood pressure adverse effects could raise questions when it goes before an FDA advisory panel.

FDA's Dermatologic and Ophthalmic Drugs Advisory Committee will review the immunosuppressive drug at its June 28 meeting. The agency granted the drug priority review status in March, with a Prescription Drug User Fee Act review deadline of August 4. The company also has filed for approval with the European Medicines Agency.

Luveniq, also known as LX211, is the oral form of voclosporin, a calcineurin inhibitor that Lux has in-licensed for ophthalmic indications from the Canadian biopharma Isotechnika Pharma, which discovered the molecule and is currently studying it for the treatment of psoriasis and the prevention of organ rejection in kidney transplant patients. "All studies to date suggest that voclosporin is more potent and less toxic than ... [other] calcineurin inhibitors," Isotechnika says on its Web site.

In two clinical trials in which patients took the drug twice daily at a dose of 0.4 mg/kg, 8.2 percent of subjects experienced adverse effects on renal function - a decrease from baseline of 30 percent or more in glomerular filtration rate and twice the rate of those on placebo. The active arm patients also suffered from higher blood pressure, with a mean increase in systolic pressure of 6 mm Hg. Lux termed these effects "moderate and manageable," adding that 5 percent of patients also had abnormal hair growth.

Uveitis is a group of non-infectious but serious eye conditions that can lead to severe vision loss or substantial morbidity from steroid use. In one of the studies Lux sponsored, 232 patients with clinically inactive uveitis were enrolled at 57 sites in North America, Europe and India. The drug "reduce[d] recurrence of inflammation by 50 percent over placebo at the 0.4 mg/kg twice daily dose (p<0.05) and may therefore effectively increase the interval between inflammatory relapses to 24 months compared to 10 months with placebo," Bahram Bodaghi, who presented the results at last October's meetings of the American Association of Ophthalmology and the associated American Uveitis Society, said in a statement.

A separate Lux-sponsored study investigated LX211 in 218 patients with active, sight-threatening uveitis affecting the posterior segment of the eye, and found the 0.4 mg/kg dose to be statistically significantly superior to placebo at controlling inflammation and preserving vision at weeks 16 and 24. Patients were able to cut back on corticosteroids to 5 mg per day or less. Lux highlighted "the ability of LX211 to control the inflammation that characterizes this potentially blinding eye disease and significantly reduce its rate of recurrence."

Also in October 2009 privately held Lux announced that it had raised $50 million in a private placement to fund the rollout of Luveniq (Also see "Lux Bioscience Brings In $50 Million To Take Luveniq To The Finish Line Alone" - Pink Sheet, 19 Oct, 2009.).

- Martin Berman-Gorvine ([email protected])