Daclizumab -- how does it fit in

Why did Facet Biotech Corporation (FACT) shareholder's reject Biogen Idec's (BIIB) unsolicited tender offer ($17.50)?

Maybe they were waiting for the release of the CHOICE data ($16.71).

The Lancet Neurology released Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta online in advance of print publication in April 2010

(http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70033-8/fulltext#article_upsell).

So, how does the data on this subcutaneous (under the skin) anti-CD25 monoclonal antibody (which causes an increase in CD56bright natural killer cells) compare to data from other MS disease modifying agents?

In this study, participants wither received high dose Daclizumab plus interferon beta, low dose Daclizumab plus interferon beta or placebo plus interferon beta -- this reminds of the study design of the phase III AFFIRM study of Tysabri plus Avonex vs. Avonex alone. The endpoint in the 6-month phase II CHOICE study of new or enlarged Gadolinium enhancing lesion on brain MRI is different from the enfpoints in the AFFIRM (and other) studies. There was a mean of 4.75 in the interferon alone group and 1.32 in the high dose Daclizumab plus interferon group. This is a fairly active group of relapsing MS patients since there are so many new (or enlarged) Gadolinium enhancing lesions despite all patients being on interferon beta.

Although we are looking at slightly different MRI outcomes and certainly different time periods, let's look at a few of the Tysabri, Fingolimod and Cladribine trials:

2-year AFFIRM (Tysabri plus Avonex vs. Avonex alone):

Number of Gadolinium enhancing lesions:

0.1 vs. 0.8

Number of new or enlarging T2 hyperintense lesions:

0.5 vs. 2.4

1-year TRANSFORMS (Fingolimod/Gilenia [here low 0.5 mg dose only] vs. Avonex):

Number of Gadolinium enhancing lesions:

0.23 vs. 0.51

Number of new or enlarging T2 hyperintense lesions:

1.7 vs. 2.6

2-year CLARITY (Cladribine [here low 3.5 mg/kg dose only] vs. placebo):

Number of Gadolinium enhancing lesions:

0.12 vs. 0.91

Number of Combined Unique lesions:

0.43 vs. 1.72

Number of Active T2 lesions:

0.38 vs. 1.43

6-month CHOICE (Daclizumab [here high 2 mg/kg dose] plus INF vs. INF alone):

Number of new or enlarged Gadolinium enhancing lesion:

1.32 vs. 4.75

So, no matter how you look at it, the patients in the CHOICE study had more active MRIs (albeit, this is only a 6-month study).

So, were the FACT shareholders right in rejecting BIIB's bid?

What do you think?

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org