LX211 submission for approval in US and Europe

We have been asked by a number of  our members if we know anything about the about the progress of the LX211 trials which highlighted LX211 as potential disease modifying therapy for noninfectious uveitis.  Birdshot is a non infectious form of posterior uveitis.

In February we read that Lux Biosciences was preparing to file for US and European approval.  If the drug is approved it will be the first drug licencensed in the US and Europe specifically for uveitis.  We would assume that licencing in the UK would be likely to follow this.

On 4th August, Isotechnika Pharma Inc, Lux’s US partners sent out a press release which stated that before approval would be given in the US, further trials were needed to check out the drugs safety.  It stated that approval remained on course for Europe. http://micro.newswire.ca/release.cgi?rkey=1808048256&view=64134-0&Start=0&htm=0

We are not sure how long the process takes for licencing to occur but we are watching out for developments.

One thought on “LX211 submission for approval in US and Europe

  1. ARVO: Mixed Results with Investigational Uveitis Drug
    By Charles Bankhead, Staff Writer, MedPage Today
    Published: May 05, 2009
    Reviewed by Zalman S. Agus, MD; Emeritus Professor
    University of Pennsylvania School of Medicine. Earn CME/CE credit
    for reading medical news

    FORT LAUDERDALE, Fla., May 5 — An investigational therapy for uveitis outperformed placebo in one randomized clinical trial but produced mixed results in two other studies reported here. Action Points
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    Explain to patients that studies of a drug for noninfectious eye inflammation showed potential for improving the condition.

    Only one of three studies met its specified endpoint.

    Note that these studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
    In the positive study, the oral calcineurin inhibitor voclosporin (LX211, Luveniq) led to >1 step improvement in vitreous haze, compared with placebo, James Rosenbaum, M.D., of Oregon Health and Science University in Portland, said at the Association for Research in Vision and Ophthalmology (ARVO) meeting.

    The second study showed a statistically significant reduction in eye inflammation with voclosporin compared with placebo (P=0.045), but did not meet the primary endpoint of all-cause therapeutic failure.

    In the third trial, voclosporin failed to distinguish itself from placebo in the uveitis subgroup with anterior inflammation.

    “Based on the results of the LUMINATE trial program, LX211 appears to offer a therapeutic and safety profile that would meet the critical need for an oral medication for uveitis,” Dr. Rosenbaum said in a statement.

    “LX211 is not a corticosteroid, but allows the reduced use of corticosteroids, which in turn reduces the serious side effects associated with those drugs.”

    The studies also demonstrated voclosporin’s steroid-sparing potential, as patients treated with the agent were able to taper their steroid dose to 5 mg/d or less, he added.

    The LUMINATE clinical trials program comprised three randomized, placebo-controlled studies. Investigators in the U.S., Canada, Europe, and India enrolled a total of 558 patients with noninfectious uveitis.

    In all three trials, patients were randomized to placebo or to one of three doses of voclosporin (0.2, 0.4, or 0.6 mg/kg bid) and treated for 24 weeks.

    Collectively, the trials showed that the 0.4 mg/kg dose offered the best balance of safety and efficacy.

    The LX211-01 trial involved 218 patients with posterior disease. The primary endpoint was the mean change in vitreous haze. Voclosporin led to significantly greater improvement at week 16 (P=0.008) and week 24 (P=0.04).

    LX211-02 involved 232 patients with quiescent disease. The primary endpoint was all-cause therapeutic failure at six months, a composite outcome that included events such as disease recurrence, discontinuation for adverse effects, and discontinuation for other reasons.

    According to Dr. Rosenbaum, withdrawals unrelated to efficacy diluted the statistical power required to demonstrate a significant treatment effect.

    However, a protocol-specified analysis that accounted for the withdrawals showed a 50% greater reduction in inflammation with voclosporin compared with placebo (P=0.045).

    LX211-03 involved 108 patients with predominately anterior-chamber disease. Treatment with voclosporin reduced the cellular response by 60% to 75% compared with baseline, but patients in the placebo group also improved. As a result, voclosporin did not demonstrate superiority to placebo.

    Voclosporin was associated with a higher incidence of adverse effects than placebo.

    They included ?30% decrease in glomerular filtration rate in 8.2% of patients, versus 4.1% in the placebo group; a 6 mm Hg increase in systolic blood pressure, and hirsutism in 5% of patients.

    Otherwise, voclosporin had a safety profile similar to that of placebo, said Dr. Rosenbaum.

    The LUMINATE clinical trial program was funded by Lux Bioscience.

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