Zosano Pharma Corporation announces that its lead product candidate, M207, achieved both co-primary endpoints of pain freedom and most bothersome symptom freedom at 2 hours in the recently completed ZOTRIP trial. The ZOTRIP pivotal efficacy study was a multicenter, double-blind, randomized, placebo-controlled, dose-ranging trial comparing three doses (1.0mg, 1.9mg and 3.8mg) of M207, a novel transdermal therapeutic, to placebo for a single migraine attack. A total of 589 subjects were enrolled at 36 sites across the US. The 3.8mg dose achieved significance in the secondary endpoints of pain freedom at 45 minutes and 1 hour and showed durability of effect on pain freedom at 24 and 48 hours. Additionally, M207 was not associated with any Serious Adverse Events (SAEs).
The 3.8mg dose of M207 achieved statistical significance for both co-primary endpoints at two hours:
| Primary endpoint | Placebo | 3.8mg M207 | p–value | ||
| Pain freedom | 14.3 | % | 41.5 | % | 0.0001 |
| Most bothersome symptom free | 42.9 | % | 68.3 | % | 0.0009 |
Furthermore, secondary endpoints measuring pain freedom at additional time points for the 3.8mg dose of M207 showed M207 superior to placebo with a nominal p-value less than 0.05:
| Pain Freedom | Placebo | 3.8mg M207 | p–value* | ||
| Pain freedom at 45 minutes | 5.2 | % | 17.1 | % | 0.0175 |
| Pain freedom at 60 minutes | 10.4 | % | 26.8 | % | 0.0084 |
| Pain freedom at 24 hours | 39.0 | % | 69.5 | % | 0.0001 |
| Pain freedom at 48 hours | 39.0 | % | 64.6 | % | 0.0013 |
M207 was well-tolerated with no SAEs
- Overall, 13 subjects (3.9%) reported pain at the application site; application site pain was reported as mild in all but 3 subjects;
- The most frequently reported adverse event was redness at the application site (18.3% of subjects). All cases of redness resolved;
- Additionally, 5 (1.5%) patients across M207-treated groups reported dizziness vs 0% on placebo.
Stewart Tepper, MD, Professor of Neurology, Geisel School of Medicine at Dartmouth and Director of the Dartmouth Headache Clinic commented, “The ZOTRIP study was successful from the dual perspectives of meeting the co-primary endpoints and no serious adverse events. The study demonstrated a statistically significant 2-hour pain freedom response rate with a low placebo rate for the primary endpoint. The data also indicate a durability of effect at 24 and 48 hours, and meaningful pain freedom rate at 1 hour. If approved by the FDA, M207 has the potential to become an important treatment option for those suffering from migraine.”
Overall, higher pain freedom rates were achieved on all doses after 60 minutes over placebo. While the 1.0mg and 1.9mg doses of M207 produced p-values less than 0.05 in pain freedom at two hours, they did not produce a p-value below 0.05 for the co-primary endpoint of freedom from most bothersome symptom at two hours.
“ZOTRIP was designed to be a dose-ranging study, as well as a registration study. We are very pleased by the results for the 3.8mg dose, and look forward to continuing the development of M207 towards filing an NDA and working to bring this novel therapy to patients suffering from the incapacitating effects of migraines,” said Konstantinos Alataris PhD, President and Chief Executive Officer of Zosano.
Filed Under: Drug Discovery
