EMA Panel Backs Daclizumab (Zinbryta) for Multiple Sclerosis

Daclizumab is given by self-administered subcutaneous injection once a month.
The humanized monoclonal antibody selectively binds to the high-affinity interleukin-2 receptor subunit (CD25) expressed at abnormally high levels on T cells in patients with MS. Daclizumab offers a targeted mechanism of action that does not cause broad and prolonged immune cell depletion, the company notes in a news release.
According to the CHMP opinion, the benefits of daclizumab include its ability to reduce the annualized relapse rate and risk for disability progression.
The positive CHMP opinion is based on results from two clinical trials. In the DECIDE study, daclizumab 150 mg administered subcutaneously every 4 weeks showed a reduced relapse rate and fewer new lesions on MRI compared with interferon β-1a (Avonex, Biogen) injected intramuscularly weekly.
In the placebo-controlled SELECT study, daclizumab reduced relapse rates and had positive effects on key measures of MS disease activity relative to placebo.
The most common side effects with daclizumab seen in clinical trials are elevations of liver enzymes and hepatic injury, cutaneous events, infections, gastrointestinal disorders, and depression. The CHMP recommends that daclizumab be prescribed by physicians experienced in the management of MS.
For more information on the mechanism of action of daclizumab check Gavin’s post ~6 months ago. Personally, I am concerned about yet another drug with a potentially significant secondary autoimmunity problem, however the EMA was happy with daclizumab’s risk:benefit profile.

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  • This drug just targets Tregs instead of wiping out everything like HSCT.

    So how does this fit in with the current montra that MS is driven by B-cells (Rituximab, etc.)?

    • It think this idea is wrong…just like the MS is driven by B cells is wrong too (an opinion that may be wrong too).

      Yes it does target T regs..but it depetes them. If we follow MS dogma then this should make MS worse but it doesn't so what does this say about Tregs or dogma? The autoimmunites induced are distinct from those induced by alemtuzumab and maybe a problem of removal of T reg?

      Does it actually do what it was orginally used for and gets rid of activated T cells?

      Does it work by boosting NK cells that get rid of an infection e.g. EBV

      The big question is how is this going to be positioned?

      Based on the results its effect on relapse is not in the same league as alemtuzumab, natalizumab but more like dimethyl fumarate.

      Daclizumab is part Biogen verse part Abbvie verses dimethyl fumarate which is Biogen. Is Biogen going to promote a product to compete against its own product?

      We will now see

  • Daclizumab efficacy is highly overestimated. The trick is through the way SELECT study data were presented:

    A year prior to the study the placebo group, the Dac150 and the Dac300 group had ARR (Annualised Relapse Rate) of 1.3, 1.4 and 1.3 respectively.
    After the end of the one-year study the new ARRs were 0.46, 0.21 and 0.23

    The presentation-interpretation of the data is that Dac150 reduced relapses by 54% = (0.46-0.21)/0.46.
    54% reduction of ARR sounds amazing, but is totally misleading because:
    a) compares results of different patient groups
    b) compares results under different patient conditions (nothing-placebo, nothing-Dac150)

    A more direct approach would be to compare the ARR of the SAME groups before and after treatment. That way, (a) above is eliminated, and we get:
    – (1.3-0.46)/1.3 = 64% reduction for placebo
    – (1.4-0.21)/1.4 = 85% reduction for Dac150
    – (1.3-0.23)/1.3 = 82% reduction for Dac300

    Thus, only 21% reduction of relapses for Dac150 compared to placebo. NOT very impressive indeed, although much closer to reality.

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