Replies to post #106864 on Biotech Values

[biomaven0]

I don't have access to the published article, so I was going from their PR:

In both PREEMPT studies, patients treated with BOTOX® experienced a significantly greater decrease in the frequency of headache days from baseline compared to patients treated with placebo at the week 24 primary endpoint (7.8 and 9.2 fewer days for the BOTOX® group, versus 6.4 and 6.9 days for the placebo group, respectively). Also at week 24, patients treated with BOTOX® experienced a total cumulative reduction in headache hours by 107 and 134 hours, respectively, compared to 70 and 95 hours, respectively, in patients treated with placebo.

Their first sentence is ambiguous as to whether they meant over the whole period or over the last month, but if you look at the reduction in hours - 107 vs 70, that is certainly cumulative and is 4.5 days total vs. 2.9 days worth over the cumulative 24 week period. So my point about clinical significance is still valid - basically 1.5 days less pain over a 24 week period.

Now that I think more about it though, your interpretation of the endpoint certainly makes more sense than mine - I'll have to try to get access to the actual paper to confirm.

Peter

[biomaven0]

I checked the abstracts of the two studies. The first is again ambiguous, but the second confirms your interpretation - it is change in headache frequency in the last month compared with baseline.

Here are the two studies:

Cephalalgia. 2010 Jul;30(7):793-803. Epub 2010 Mar 17.
OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.

Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT 1 Chronic Migraine Study Group.

Swedish Neuroscience Institute, USA. [e-mail]
Abstract

OBJECTIVES: This is the first of a pair of studies designed to assess efficacy, safety and tolerability of onabotulinumtoxinA (BOTOX) as headache prophylaxis in adults with chronic migraine.

METHODS: The Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1 (PREEMPT 1) is a phase 3 study, with a 24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxinA (155 U-195 U; n = 341) or placebo (n = 338) (two cycles). The primary endpoint was mean change from baseline in headache episode frequency at week 24.

RESULTS: No significant between-group difference for onabotulinumtoxinA versus placebo was observed for the primary endpoint, headache episodes (-5.2 vs. -5.3; p = 0.344). Large within-group decreases from baseline were observed for all efficacy variables. Significant between-group differences for onabotulinumtoxinA were observed for the secondary endpoints, headache days (p = .006) and migraine days (p = 0.002). OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events.

CONCLUSIONS: There was no between-group difference for the primary endpoint, headache episodes. However, significant reductions from baseline were observed for onabotulinumtoxinA for headache and migraine days, cumulative hours of headache on headache days and frequency of moderate/severe headache days, which in turn reduced the burden of illness in adults with disabling chronic migraine.

Cephalalgia. 2010 Jul;30(7):804-14. Epub 2010 Mar 17.
OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial.

Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, Silberstein SD, Brin MF; PREEMPT 2 Chronic Migraine Study Group.
University of Essen, Germany. [e-mail]
Abstract

OBJECTIVES: This is the second of a pair of studies designed to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX) for prophylaxis of headaches in adults with chronic migraine.

METHODS: PREEMPT 2 was a phase 3 study, with a 24-week, double-blind, placebo-controlled phase, followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections of onabotulinumtoxinA (155U-195U; n = 347) or placebo (n = 358) every 12 weeks for two cycles. The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21-24 post-treatment.

RESULTS: OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint, frequency of headache days per 28 days relative to baseline (-9.0 onabotulinumtoxinA/-6.7 placebo, p < .001). OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons. OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few patients (3.5% onabotulinumtoxinA/1.4% placebo) discontinued due to adverse events.

CONCLUSIONS: The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine. Repeated onabotulinumtoxinA treatments were safe and well tolerated.