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Daclizumab trial for relapsing-remitting MS begins

ZenapaxActive Comparator Study Designed to Examine the Safety and Efficacy of Daclizumab Formulated for Monthly Subcutaneous Dosing.

Biogen Idec and Abbott today announced enrollment of the first patient in a global Phase III study evaluating the efficacy and safety of daclizumab compared to interferon beta-1a (Avonex(R)) in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS).

The trial, called DECIDE, will investigate a subcutaneous formulation of daclizumab intended for monthly administration, which has the potential to provide a new immunomodulatory approach for treating MS. Under the terms of the collaboration agreement, Biogen Idec will make a $30 million milestone payment to Abbott. This payment is due upon enrollment of the first patient in the DECIDE trial.

"Despite significant advances in MS therapy, many patients continue to experience disease activity. The MS community is eager for new treatment approaches," said Ludwig Kappos, M.D., Head, MS-Research Group, University Hospital, Basel, Switzerland, and lead investigator for the study. "As shown in previous studies, daclizumab appears to selectively target immune cells that are thought to become activated in MS and cause damage to the central nervous system."

DECIDE is a global Phase III, randomized, double-blind, active-comparator study expected to enroll approximately 1,500 RRMS patients in 28 countries. The trial will investigate a subcutaneous formulation of daclizumab intended for once-monthly administration as a monotherapy compared to treatment with interferon beta 1-a, one of the most common treatments for MS. Daclizumab is also being investigated in the ongoing Phase IIb registration-enabling SELECT trial, which is evaluating the efficacy and safety of monthly subcutaneous doses of either 150 mg or 300 mg of daclizumab monotherapy.

"The DECIDE study builds on the positive results we saw in the CHOICE trial, which showed that daclizumab, when added to interferon beta, significantly reduced MS lesions compared to interferon beta therapy alone," said Alfred Sandrock, M.D., Ph.D., Senior Vice President of Neurology Research and Development at Biogen Idec. "Initiating this trial demonstrates our commitment to developing new treatment options for patients who suffer from this terrible disease."

"Initiating the Phase III DECIDE trial is a tremendous milestone for the collaboration as it brings daclizumab one step closer to becoming a potential new treatment option for patients with MS," said Eugene Sun, M.D., Vice President, Global Pharmaceutical Clinical Development, Abbott. "Extensive preclinical and clinical experience with daclizumab suggest this drug holds promise as a new approach for the treatment of MS, and we look forward to expanding our knowledge further with the DECIDE trial."

Multiple sclerosis, one of the most common neurological disorders, affects more than 2.5 million people worldwide. In MS, certain immune cells, called T-cells, become activated and are believed to migrate to the central nervous system (CNS), releasing cytokines that injure nerve fibers in the CNS and cause the symptoms of MS.

Daclizumab is a humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at low levels on resting T-cells and at high levels on T-cells that are thought to become activated in response to MS. Daclizumab is believed to work by selectively targeting these activated T-cells without causing general T-cell depletion.

Data from the Phase II CHOICE trial demonstrated that daclizumab 2mg/kg administered subcutaneously every two weeks in combination with interferon beta (IFNB) therapy led to a 72 percent reduction in the number of new or enlarged MS lesions when compared to IFNB therapy alone in patients with active, relapsing forms of MS. Additional analysis from the study revealed that daclizumab led to an increase of a subset of natural killer cells (CD56bright NK cells) that help regulate the immune system. This increase was associated with a significant reduction in MS lesion formation. The incidence of common adverse events was similar in all treatment groups. Some serious adverse events occurred in daclizumab treated patients, which were most commonly infections that resolved with standard interventions.

About DECIDE

DECIDE (Daclizumab HYP Efficacy Compared to Interferon Beta 1-a Study for Multiple Sclerosis) is a two- to three-year, Phase III, muliticenter, double-blind, randomized, parallel-group, monotherapy, active-control study designed to determine the efficacy and safety of daclizumab versus interferon beta 1-a, one of the most common MS treatments, in patients with RRMS. The trial is expected to enroll approximately 1,500 RRMS patients in 28 countries. The study will include patients between the ages of 18 to 55 years with an Expanded Disability Status Scale (EDSS) score ranging from 0.0 to 5.0.

The primary objective of the study is to determine the efficacy of daclizumab compared to interferon beta 1-a in preventing MS relapse, with annualized relapse rate as the primary endpoint. The study will also examine the efficacy of daclizumab compared to interferon beta 1-a in slowing functional decline and disability progression and in maintaining quality of life.

During the 96- to 144-week treatment period, all study participants will receive either a subcutaneous injection of daclizumab 150 mg once every four weeks or weekly injections of interferon beta 1-a.

About Daclizumab

Daclizumab is a humanized monoclonal antibody that binds to the CD25 alpha subunit of the high affinity IL-2 receptor. CD25 is expressed at low levels on resting T-cells (immune cells) and at high levels on T-cells that can become activated in response to autoimmune conditions such as MS. Daclizumab is believed to work by selectively binding to and inhibiting this receptor on activated T-cells without causing T-cell depletion. Daclizumab is an investigational agent in clinical development for the treatment of MS under a collaboration between Facet Biotech, acquired by Abbott in April 2010, and Biogen Idec. Daclizumab is currently being studied in two registrational clinical trials in patients with MS.

Source: Biogen Idec (24/05/10)

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Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.

Zenepax (as the drug is called here) is a WONDERFULLY effective drug. I have been on it once a month IV for more than a year. It works great and I have experienced no side effects.

HOWEVER - there are only a very few of us taking this drug outside of the clinical trials. but the company sent a letter to all doctors telling it that the drug was no longer available after December.

I managed to keep getting it until last month. The backsliding has already started. The company is unwilling to help the handful of patients on this drug, but is starting Phase II trials, which if are successful as expected will enable them to go on and make literally many millions off MS patients.

They cannot let us continue to pay $5,000 a month for taking this drug while the can manage to make it available to those who will enable them to get the FDA approval they need to make massive profits????

THIS SUCKS !!!!

I am going to have the CCSVI prodecude, but I should be able to continue to take this drug.

I am in this study. I have a sneaky suspicion that I am getting avonex though since I often have back pain and flu like symptoms the day after the injection.

When do you find out which arm you are in? This is a LONG study.

Hi,
I had my first injection of daclizumab or placebo last friday. The same day I got avonex or placebo. I have no idea what am I taking. Which one is a real drug? No idea.

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Polish, 30yrs, dx 2000 RRMS, EDSS 5.

liberated in february the 2nd 2010:). Currently on double blind clinical trial with Avonex/Daclizumab.

Everyone here appears to be in some way on the trial or historically on it, but this is my first real introduction to Daclizumab. So I searched on Google to see if there was any data on EDSS. And whoa! http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002600/ If you click on the diagram it takes you to the full data (obviously a tiny study) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002600/table/table1-1756285609337992/ but every one had an improvement in EDSS, as opposed to the standard increase.

However, it does appear to be high on the side effects, which are individually excruciatingly detailed in the above study.

Do you think there is some rebound effect beyond the natural course of MS; such as that seen with Tysabri?
I would guess you also experienced an EDSS improvement. Did you find it was the biggest change at the beginning then possibly slow improvement after, or was it a fairly steady over time improvement?

I am also on this trial. I started Oct.17/10. I believe I am on Avonex just because of the side effects I deal with every week.

I have been in the Decide trial for over two years now. Not certain which drug I am on. I believe I am on the Daclizumab, simply because I had been on the Avonex previously for over 2 years and the side effects were horrible for me.
Now I feel okay afterwards.

April clinic visit will be week 144 in Decide Trial! Hoping for two things:
1. An extension
2. Possibly find out which drug I have been on for the last two years.
My nurse did mention that she has new consent forms for me to sign next week at my Week 140 visit, so my fingers are crossed for good luck on both counts. Will update with news next week!

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RRMS dx 2006. EDSS <1 (so far) Enrolled in clinical trial since 2011.

Hello Rocketdog- I hope you are doing well. What did you find out????

Thanks!

Hello Cure! Well, no news yet. The trial was taken over by another CRO so I will find out something on my next visit, week 144 which is April 8.
I will be sure to post...are you in this trial too?
Hope you are well also!

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RRMS dx 2006. EDSS <1 (so far) Enrolled in clinical trial since 2011.

err.. was that a shout out to me? or to WantingACure? or a statement on this drugs effects?
If your asking me, then, No, I am not in this trial, but am interested in this treatment!

Sorry! It was a reply to wanting a cure, but it was nice to hear from you too!
So, yesterday was week 144, end of trial. Full day of testing~ bloodwork, EDSS, MRI, VFT, all of the acronyms you can think of. Then I got the new consent forms to sign!! I am now officially on the Daclizumab for the next 2-3 years (barring any SAE's of course). Still no word on which I have been taking for the last 2.5 yrs, but that's okay.
One sub-Q a month. No more IM once a week! They will still be testing for liver function and everything else to monitor for side effects.
EDSS is still zero, 500m walk in about 2.5mins, and still have the cognitive skills that allow me to work. Hoping I can still play volleyball this summer!
I wish anyone else in these trials will chime in on their experiences? Positive, negative, neutral...
Thanks!

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RRMS dx 2006. EDSS <1 (so far) Enrolled in clinical trial since 2011.

What was your EDSS before you started treatment?

Unless I am in a relapse, my EDSS is usually between 0-1. Brain fog? Meh, that's another story. I've had very little of that with the Dac HYP. Interferons = total wipeout at least one or two days a week. Plus the fever, chills, pain...
How about you?

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RRMS dx 2006. EDSS <1 (so far) Enrolled in clinical trial since 2011.