Zosano Pharma Corporation (ZSAN) declares 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 accomplished 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. In Addition To, M207 was not associated with any Serious Adverse Events (SAEs).
M207 was well-tolerated with no SAEs
- Overall, 13 subjects (3.9%) stated pain at the application site; application site pain was stated as mild in all but 3 subjects;
- The most frequently stated adverse event was redness at the application site (18.3% of subjects). All cases of redness resolved;
- In Addition To, 5 (1.5%) patients across M207-treated groups stated 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 noteworthy2-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, in addition to a registration study. We are very happy 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.
The ZOTRIP Phase 3 Trial Design:
The ZOTRIP pivotal efficacy study was a multicenter, double-blind, randomized, placebo-controlled trial comparing three doses of M207 (1.0mg, 1.9mg, and 3.8mg) to placebo for the treatment of a single migraine attack. Subjects were enrolled in the ZOTRIP trial at 36 centers across the United States. Those recruited into the trial had a history of at least one year of migraine episodes with or without aura. Upon recruitment, the subjects entered a run-in period that ensured they met the key eligibility criteria of 2-8 migraine attacks per month, which was documented using an electronic diary or an app on their cell phone. Subjects also identified their most bothersome symptom and indicated the presence or absence of nausea, phonophobia or photophobia, during the episodes in the run-in period. Successfully screened subjects were then randomized into the treatment/dosing period in which they had 8 weeks to confirm and receive blinded treatment for a single migraine attack, termed “qualifying migraine.” In which the most bothersome symptom had to be present.
During a qualifying migraine, subjects scored the severity of pain on a 4-point scale, and the presence or absence of migraine associated symptoms (photophobia, phonophobia or nausea), starting pre-dose and then at several intervals over 48 hours post-dose.