Good news: top-line results from the Daclizumab phase 2b study

G
Press release WESTON, Mass. & ABBOTT PARK, Ill., Aug 09, 2011 (BUSINESS WIRE)

Biogen Idec (NASDAQ: BIIB) and Abbott (NYSE: ABT) announced positive top-line results from SELECT, a global, registrational Phase 2b clinical trial designed to evaluate the investigational compound daclizumab high-yield process (DAC HYP) in people with relapsing-remitting multiple sclerosis (RRMS) over one year. Results showed that DAC HYP, administered subcutaneously once every four weeks, significantly reduced annualized relapse rate by 54 percent in the 150 mg dose arm (p< 0.0001) and 50 percent in the 300 mg dose arm (p=0.0002) compared to the placebo arm at one year. DAC HYP met key secondary endpoints for the 150 mg and 300 mg arms, respectively, providing a highly statistically significant reduction in the cumulative number of new gadolinium-enhancing (Gd+) lesions between weeks eight and 24 (69%; 78%); in the number of new or newly enlarging T2 hyperintense lesions at one year (70%; 79%); and in the reduction in the proportion of patients who relapsed (55%; 51%). DAC HYP also showed a trend toward improvement in quality of life measures at one year.

The SELECT trial also investigated DAC HYP’s effect on disability progression as measured by the expanded disability status scale (EDSS) as a tertiary endpoint. Findings showed that DAC HYP reduced the risk of sustained disability progression at one year by 57 percent in the 150 mg dose arm and by 43 percent in the 300 mg dose arm compared to placebo. Additional analyses are ongoing and the companies anticipate presenting detailed data at an upcoming medical meeting.

“The exciting results for DAC HYP, along with previous clinical data, support our continued investigation of this candidate as a promising new approach to treating multiple sclerosis,” said Doug Williams, Ph.D., Biogen Idec’s Executive Vice President of Research and Development. “DAC HYP’s convenient once-monthly, subcutaneous administration, combined with a strong efficacy profile, suggest that it may provide an attractive option for MS patients. We hope to confirm the results of SELECT in our second registrational trial, DECIDE.”

“These results bring us one step closer in the development of a potential new treatment option for multiple sclerosis, an area of medicine where there continues to be a significant need for novel approaches for patients,” said Eugene Sun, M.D., Vice President, Global Pharmaceutical Clinical Development, Abbott. “We look forward to continued analysis of the SELECT data and the opportunity to present these results in full context at an upcoming scientific forum.”

In the SELECT trial, the overall incidence of adverse events and treatment discontinuations were similar in all study arms. Serious infections (2% versus 0%), serious cutaneous events (1% versus 0%) and liver function test abnormalities greater than five times the upper limit of normal (4% versus <1%) occurred more frequently in DAC HYP-treated patients than in the placebo group. There was one death in SELECT due to a complication of a psoas muscle abscess in a patient recovering from a serious skin adverse event and one in the ongoing dose blinded extension study (SELECTION) due to possible autoimmune hepatitis; a contributory role for DAC HYP in these events could not be excluded.

In addition to SELECT, DAC HYP is being studied in a Phase 3 registrational clinical trial called DECIDE, which is currently enrolling patients. DECIDE is evaluating the efficacy and safety of once-monthly subcutaneous DAC HYP as a monotherapy compared to interferon beta 1-a therapy over two to three years of treatment.

About SELECT

SELECT was a global, randomized, double-blind, placebo-controlled, one-year, dose-ranging study to determine the safety and efficacy of DAC HYP in 600 patients with RRMS. The study evaluated two doses of DAC HYP (150 mg or 300 mg every four weeks) and had a greater than 90 percent study completion rate in all treatment groups. The primary endpoint was the reduction in annualized relapse rate in patients with RRMS at one year. Secondary endpoints included the reduction in the cumulative number of new gadolinium-enhancing (Gd+) lesions between weeks eight and 24, in the number of new or newly enlarging T2 hyperintense lesions at one year, and in the proportion of patients with RRMS who relapsed, as well as improvement in quality of life measures in patients with RRMS at one year. Additional endpoints assessed the safety and tolerability of DAC HYP.

About DAC HYP

Daclizumab high-yield process (DAC HYP) is a subcutaneous formulation of daclizumab and an investigational therapy for the treatment of RRMS, the most common form of MS. DAC HYP is a humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at high levels on T cells that are thought to become abnormally activated in autoimmune conditions, such as MS. Data from previous clinical trials showed that DAC HYP increases CD56bright NK cells, which target the activated immune cells that can play a key role in MS without causing general immune cell depletion.

“Exactly how we will use Daclizumab in clinical practice is not clear. However, the fact that this will be the first drug with a well-validated response marker (CD56bright NK cells) will make it a very appealing to use. For the first time we will be able to assess who is a responder vs. a non-responder; this is something we can’t do with the other DMTs.”
CoI: Multiple; importantly I sit on the SELECT Trial steering committee that oversees the running of the trial

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

9 comments

  • SELECT study included patients from Europe and India. Could you tell us the ratio? How come India?

  • Re: "SELECT study included patients from Europe and India. Could you tell us the ratio? How come India?"

    Not sure; 97% of the study subjects were Caucasian. Therefore the number of Asian are tiny. Why not India? Asians also suffer from MS. The incidence of MS is increasing in Asia; I therefore see no reason why not to include India and other Asian countries in clinical trials. Unless you think that Asian MS, is not MS.

  • Why India? my guess: lots of never-been-treated MSers. That should make it a good place for placebo trials

  • Re: "Why India? my guess: lots of never-been-treated MSers."

    Possibly, but unlikely in view of so few Asians in the study. <3% of participants were Asian. More likely 1.3 billion people, or a third of the population on the planet, live in India. The Indian market cannot be ignored; it's potentially very big.

  • Indians are Caucasians, not Asians. My question was how many of the 600 participants were of Indian nationality and why.

  • Re: "My question was how many of the 600 participants were of Indian nationality."

    <3%

    "Why?"

    Because they had MS.

    You may want to have your cognition formally assessed; it seems if you can't read or have a problem with comprehension.

  • Re: "You may want to have your cognition formally assessed; it seems if you can't read or have a problem with comprehension."

    Anon. Please stop making personal comments. Have you made this comment about VV on the assumption that he has MS? This may be incorrect. For all we know he could be a CCSVI entrepreneur or marketeer.

    This blog will be a better place if we keep the personal comments to ourselves. Thank you.

    VV I don't know the exact number of subjects from India, but it will be very low. I agree that they most likely reason they are in this study is because the have MS and I assume the study's sponsors (Biogen-Idec and Abbott) used a CRO with an operation in India. In addition the penetration of standard DMTs in India is low, so it may be easier to recruit in India. However, this may not necessarily be the case. Finally, MS does occur in India; the incidence is increasing so it is good to know the Indian sub-continent is being included in clinical trials. In the UK there is an epidemic of MS in the Asian/Indian community; we have a large number of UK Asians/Indians in our trials.

  • Professor, when you wrote "Caucasian" you meant "European" or "of the Caucasian race"? Indians are considered to be members of the Caucasian race. This is what caused the misunderstanding.

  • What exactly do you want to know in response to 'How come India?' it's a cryptic question again.
    How come any place in the world?

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