Daclizumab extension study results: impact on progression confirmed

Another treatment option for RRMS. What about progressive MS? #MSBlog #MSResearch

"The daclizumab extension was finally published this week in the Lancet Neurology (abstract below). I first presented the results at the last year's AAN meeting in San Diego (slides below)."

"Why is daclizumab so interesting? It Is one of the drugs that dissociates relapses from disease progression; i.e. it appears to have a greater impact on disability progression than you would expect from its impact on relapses. The other drugs that do this are ibudilast and laquinimod. I suspect these agents as a class are having a greater impact on downstream neurodegenerative events than they are having on usptream inflammatory events. Saying this daclizumab does have a reasonable impact on relapse rates with a reduction in the annualised relapse rate of over 50%. Daclizumab also has a very interesting mechanism of action; it boosts a population of cells called natural killer cells (NK-cells) that are part of the innate or hard-wired immune system. NK-cells have several functions one of which is an anti-viral role."

"Could the fact that daclizumab increases NK-cells, which correlates with the drug's effectiveness, be telling us something fundamental about MS? Could MS be due to a virus and daclizumab is boosting the anti-viral response against this virus? We don't know, but we need to keep this hypothesis in mind when we interpret the results of the trials."

"Because of daclizumab's impact on disability progression, which may be independent of its impact on relapses, it needs to be tested in SPMS. At the moment we are waiting for the phase 3 daclizuamb study in RRMS to report. If this trial is positive let's hope Biogen-Idec and AbbVie have the will, and allocate the resources, to take-on SPMS or even PPMS with daclizumab. It is the least we can do for MSers with progressive disease."

Giovannoni et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial. The Lancet Neurology, 19 March 2014 doi:10.1016/S1474-4422(14)70039-0.

Background: In the SELECT trial, disease activity was reduced in MSers who received daclizumab high-yield process (HYP) for 52 weeks. The primary aim of the SELECTION extension study was to assess the safety and immunogenicity of extended treatment with daclizumab HYP.

Methods: A multicentre, randomised, double-blind, 52-week extension trial was done in 74 centres in the Czech Republic, Germany, Hungary, India, Poland, Russia, Ukraine, and the UK between Feb 13, 2009, and Oct 3, 2012. Eligible MSers were aged 18—55 years, had relapsing-remitting multiple sclerosis, and had completed the SELECT study. MSers who received placebo in SELECT were randomly assigned (1:1) to receive 150 mg or 300 mg subcutaneous daclizumab HYP every 4 weeks for 52 weeks (treatment initiation group); those who had received daclizumab HYP were randomly assigned (1:1) to continue their present dose with (washout and re-initiation group) or without (continuous treatment group) a washout period of 20 weeks. All randomisation was done with a centralised, interactive voice-response system. MSers and personnel were masked to treatment assignment, except for the site pharmacist who prepared the study drug but had no interaction with patients. The primary endpoints were the safety and immunogenicity of daclizumab HYP. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00870740.

Findings: 517 (91%) of 567 MSers who completed the SELECT trial entered SELECTION, of whom 170 were in the treatment initiation group, 173 in the continuous treatment group, and 174 in the washout and re-initiation group. 11 MSers in the treatment initiation group (6%), 13 in the continuous treatment group (8%), and ten in the washout and re-initiation group (6%) had any serious adverse event other than relapse of multiple sclerosis. One MSer in the washout and re-initiation group (300 mg daclizumab HYP) died because of autoimmune hepatitis; a contributory role of daclizumab HYP could not be excluded. Seven MSers tested positive for neutralising antidrug antibodies: one (1%) of 128 for whom data were available in the continuous treatment group (this MSer  also tested positive at SELECTION baseline), four (2%) in the treatment initiation group, and two (2%) of 129 in the washout and re-initiation group.

Interpretation: Adverse events and immunogenicity were not increased in the second year of continuous treatment with daclizumab HYP or during treatment washout and re-initiation. These results support further assessment of daclizumab HYP for relapsing-remitting multiple sclerosis.

Other posts of interest on daclizumab:

06 Jan 2014
This is interesting in that Daclizumab is a antibody therapy that appears to be working via expanding a population of immune cells called natural killer cells or NK cells. NK cells are part of our so called innate immune system ...
09 Oct 2013
MS is full of examples of this approach, e.g. interferon-beta, rituximab (anti-CD20), alemtuzumab (anti-CD52) and daclizumab (anti-CD25) therapy. The following is the proof of concept study that led to the development ...
20 Sep 2013
Havrdova E, Giovannoni G, Stefoski D, Forster S, Umans K, Mehta L, Greenberg S, Elkins J. Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the ...
28 Jul 2013
Daclizumab is a humanized monoclonal antibody that prevents interleukin-2 (IL-2) binding to CD25, blocking IL-2 signaling by cells that require high-affinity IL-2 receptors to mediate IL-2 signaling. The phase 2a CHOICE ...

15 Apr 2013
Objective: Through a retrospective analysis, the objective of this study was to determine whether daclizumab treatment reduces the rate of brain structure atrophy in comparison to a mixture of other disease-modifying therapies ...
10 Apr 2013
We assessed whether daclizumab high-yield process (HYP) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis. METHODS: We did a randomised ...
CoI: multiple

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