BARCELONA — The phase 3 DECIDE trial, showing favorable results with the investigational drug daclizumab (Biogen) in multiple sclerosis (MS), has been published in the October 8 issue of The New England Journal of Medicine (NEJM).

The results, which show a reduced relapse rate and a lower number of new lesions on MRI with the new agent vs interferon β-1a, were first reported last year at the MS Boston 2014 meeting.

The 3-month confirmed disability progression (the main disability endpoint) was not significantly improved with daclizumab, but secondary analyses did suggest that 6-month confirmed disability progression was reduced.

In addition, a new analysis from the DECIDE trial presented today at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015 conference here showed that more patients receiving daclizumab had no evidence of disease activity (NEDA) at 2 years.

"In this new analysis we found that around double the number of daclizumab patients had no evidence of disease activity after 2 years of treatment compared with those on β interferon," lead investigator, Professor Ludwig Kappos, MD, University Hospital Basel, Switzerland, told Medscape Medical News. "This means no new lesions, no relapse, and no disability progression. This is similar to what we've seen with fingolimod and alemtuzumab."

On all the DECIDE data, he added: "I would say that daclizumab is certainly on the stronger end of the spectrum in terms of efficacy when considering all the different agents available now for MS."

The drug, which is given by subcutaneous injection once a month, is awaiting approval for MS in the United States and Europe. It is a humanized monoclonal antibody that binds to CD25 (part of the interleukin-2 receptor) and so modulates interleukin-2 signaling, which is implicated in the pathogenesis of MS.

Professor Kappos added that the positioning of daclizumab will depend on the adverse effects — mainly skin reactions, which can be serious. "The efficacy is better than most first-line treatments. We don't yet know how the regulatory authorities will recommend its use," he said.

Commenting on the data for Medscape Medical News, Professor Franz Fazekas, Medical University Graz, Austria, who was co-chair at the ECTRIMS sessions at which the new data were presented, said, "NEDA is now being used in many studies and is gaining acceptance — it is a compound measure summarizing several endpoints and confirms more or less what is shown by the individual data. It adds to the concept that these new drugs really are able to stop the disease."

But he added that the NEDA definition used in this trial may not give the whole picture because it did not include brain atrophy, which is now often included in this endpoint. "In this study the improvement in the NEDA endpoint was driven by MRI results and focal disease but did not include measure of diffuse disease," he cautioned.

Professor Fazekas said it was too premature to speculate as to where daclizumab will fit in to treatment. "But the more drugs we have, the better as we will have more choice. While it was quite well tolerated in this study, I think we have to see what side effects we see on wider use."

The DECIDE trial randomly assigned 1841 patients with relapsing-remitting MS to daclizumab (150 mg every 4 weeks subcutaneously) or interferon β-1a (30 μg once a week intramuscularly) for up to 144 weeks.

The primary end point was the annualized relapse rate, which was 45% lower with daclizumab. Other results showed a 54% reduction in the number of new or newly enlarged hyperintense lesions on T2-weighted MRI.

There was no effect on disability progression in the main 12-week endpoint, which is the only disability endpoint reported in the main NEJM paper.

An additional analysis of 24-week confirmed disability progression, which was a tertiary outcome and is published as supplemental material with the paper, does suggest a better effect with daclizumab. In addition, outcomes on the Multiple Sclerosis Functional Composite (MSFC) — also in the supplemental material — suggested a better effect of daclizumab.

Table. DECIDE Results

Outcome Daclizumab Interferon β-1a P Value
Annualized relapse rate 0.22 0.39 <0.001
No. of new or newly enlarged T2 lesions 4.3 9.4 <0.001
Disability progression confirmed at 12 wk (%) 16 20 0.16
Disability progression confirmed at 24 wk (%) 13 18 0.03
MSFC score (mean change from baseline) 0.091 0.055 <0.001
No evidence of disease progression (%) 24.6 14.2 <0.0001

 

Serious adverse events were reported in 15% of daclizumab patients vs 10% of those in the interferon β-1a group. Infections were more common with daclizumab (65% vs 57%), including serious infection (4% vs 2%).

Cutaneous events, such as rash or eczema, were a common adverse effect with daclizumab (37% vs 19%). These were classed as serious in 2% vs less than 1%, respectively.

Elevations in liver aminotransferase levels that were more than five times the upper limit of the normal range occurred in 6% of the daclizumab group vs 3% of the interferon patients.

Because there was one death in a previous study in a patient who developed skin reactions while receiving daclizumab, this adverse event will be given particular scrutiny. On this, Professor Kappos commented: "The patient who died developed an infection after discontinuing daclizumab and being treated with high doses of systemic corticosteroids for a long period of time, so it seems likely that they might have been immunosuppressed."

"In DECIDE, there were cutaneous side effects and some patients discontinued treatment because of this. Patients will have to be monitored for this and they should be treated immediately with anti-inflammatories or steroids if it occurs," he added.

The DECIDE trial was supported by Biogen and AbbVie Biotherapeutics. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

N Engl J Med. 2015;373:1418-1428. Abstract

European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015. Abstract 89. Presented October 8, 2015.

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