Late Breaking News II
Saturday, October 13, 2012, 09:15 – 09:30
Primary results of the SELECTION trial of daclizumab HYP in relapsing multiple sclerosis
G. Giovannoni, R. Gold, K. Selmaj, E. Havrdova, X. Montalban, E.-W. Radue, D. Stefoski, M. McNeill, J. Rana, J. Elkins, G. O’Neill (London, UK; Bochum, DE; Lodz, PL; Prague, CZ; Barcelona, ES; Basel, CH; Chicago, US; Maidenhead, UK; Cambridge, US)
Background: The SELECTION trial was a 52-week, randomized, double-blind trial to evaluate the safety and efficacy of extended treatment with DAC HYP as well as a 24-week treatment interruption.
Methods: 517 (92%) of eligible subjects who completed treatment in the 52-week SELECT registrational trial entered the SELECTION trial. Subjects who had received placebo in SELECT (n=170) were randomized to receive monthly 150 mg or 300 mg SC DAC HYP. Subjects who had received DAC HYP in SELECT (n=347) were randomized to continue treatment at their current dose or to a 24-week treatment interruption (washout followed by treatment reinitiation at original dose). Since efficacy of the two DAC HYP dose groups were similar, results were combined for reporting.
Results: 92% (n=474) of randomized subjects completed the 52-week treatment phase of the study. Among patients who initiated treatment with DAC HYP in SELECTION, the 52-week ARR was reduced by 59% compared to the prior year (0.18 vs. 0.43; p<0.001) and the percent of subjects with confirmed 3-month disability progression was reduced by 50% compared to the prior year (5% vs. 10%; p =0.033). Among patients randomized to remain on continuous treatment with DAC HYP over 2 years, the ARR from year 1 was sustained during year 2 (0.148 vs. 0.165) while there were fewer new/newly enlarging T2 lesions in year 2 versus year 1 (1.2 vs. 1.85; p =0.032). After 2-years of DAC HYP therapy, 88% were free of confirmed disability progression. Among subjects randomized to treatment interruption, there was no evidence for disease rebound (mean Gd+ lesions at pre-treatment baseline vs. end of washout: 1.6 vs. 1.1). There was one death in the trial due to autoimmune hepatitis in the 300 mg treatment interruption group. The incidence of serious infections (2% vs. 2%) and serious cutaneous events (1% vs. 1%) was similar in SELECTION compared to SELECT while AST/ALT elevations >5x ULN were less common (1.5% vs. 4%). In subjects who remained on continuous treatment in the low-dose group (DAC HYP 150 mg), there were no AST/ALT elevations >5x ULN or serious cutaneous events during the second year of treatment.
Summary: These results support the efficacy findings of the SELECT trial and indicate that the efficacy of DAC HYP is sustained through the second year of therapy. Risks appeared similar compared to the first of year of treatment, and there was no evidence of rebound disease activity after a 24-week washout.
“These results are very interesting. Daclizumab seems to be having an impact on disability beyond what you expect from its impact on relapses. Could Daclizumab be targeting a process responsible for the degenerative component of MS? We will need to wait and see; a large phase 3 trial is currently underway to answer this question. Why doesn’t Biogen-Idec/Abbott do a trial in progressive MS to answer this question? I have asked them this. I think they should do it sooner than later; progressive MSers deserve it!”
CoI: multiple
"Since efficacy of the two DAC HYP dose groups were similar"If Daclizumab had any effect on the true pathology of MS, shouldn't there be some noticeable dose related outcome?ARR of 0.43 for the placebo group in SELECT means that most patients taking placebo did not have a single relapse during the trial period. There were 0.43*170=73 relapses in total for 170 placebo patients during 52 weeks. This indicates that relapse was a rather uncommon event that affected only a minority of patients. Therefore, drawing conclusions for the whole group is erroneous. "the percent of subjects with confirmed 3-month disability progression was reduced by 50% compared to the prior year (5% vs. 10%; p =0.033)"3-month disability progression has zero prognostic value for long term disability. The 50% reduction is only relative, the absolute is only 5%, but of course that way it doesn't sound much. In other words, the above statement is just an empty shirt.
re 'shouldn't there be some noticeable dose related outcome?': not necessarily, not if the lower dose was sufficient
Suffient to exert the "Hypothesized Immunomodulatory effect" according to the presentation? You can't realy prove this since the exact mechanism of action is, as always, unknown.Using Occam's razor you should take the simplest explanation first, that is the dose is irrelevant because it has nothing to do with the real driving mechanism of damage in MS.
VV your 'no effect' explanation is no simpler than mine. When I have a fever and bodyache, a double dose of panadol has the same effect as the recommended dose
The triple post wasn't intentional. I don't know how it happened
Triple post is no more
"a double dose of panadol has the same effect as the recommended dose"What effect is that Roshni? 33% reduction in bodyache? The "sufficient dose" explanation is not as simple, since it presupposes the soundness of the autoimmune theory. The other explanation has no prerequisites.
A trial in progressive MS would answer the question and, cynically, progressive MS is a huge untapped market for Pharma. I think you're right, this should be done.
PPMS is not a huge market, simply because there arent't enough consumers for sufficient time around to get tricked by reduced lesions and relapses. In PPMS one is face to face with hard progression. This so called "unmet need" is proof that treatments of RRMS are hi-tech, exprensive and often venomous distractions.
No guessing what type of MS VV has? Obviously not PPMS. What planet are you on; 15% of people with MS have PPMS. Of course there is unmet need; I can see the interventional radiologists rubbing their hands in glee. Charlatans!
90% of all new patients will eventually develop progressive forms of MS. In fact MS is progressive right from the start, the distinction is really made to ease the drug selling process. But it is not about the numbers, anon. It's about prospective profit. No one can sell anything useful to PPMS patients, so in Pharma eyes there is no market there. But a RRMS patient is another story! He will surely be around for at least 20-30 years before realising that anything he has done has been in vain. Clearer now?
Get real, what is clear you are talking such a load of mushroom food
I think it's important to state that VV appears to have no formal expertise in the field of MS and the opinions expressed in his/her posts are entirely his/her own.In our opinion comments such as the ones above are merely obfuscations from someone who is a proselytiser for CCSVI and "liberation therapy".It's good to have a debate but when your opponent is a professional goalpost shifter the value of such a debate is frequently minimal.
That's right MD2. I am not a doctor, but unless you have MS too, i know more about it than you.