The FDA accepted an NDA for Zosano’s ADAM zolmitriptan (Qytripta) in the acute treatment of migraine in early March, with a PDUFA date set for mid-October 2020.
Egilius Spierings, MD
Zosano Pharma has announced that new post-hoc efficacy analyses of its adhesive dermally applied microarray (ADAM) zolmitriptan (Qytripta; previously known as M207) from its open-label, long-term safety study suggest that the results were consistent with what was observed in the pivotal phase 2/3 study results.1
Presented virtually at the 2020 American Headache Society (AHS) Annual Meeting, the data suggest that across all 6 efficacy measurements—pain freedom at 2 hours, pain relief at 2 hours, sustained pain freedom for 2 to 24 hours, sustained pain freedom for 2 to 48 hours, sustained pain relief for 2 to 24 hours, and sustained pain relief for 2 to 48 hours—the migraine headaches treated with 3.8-mg ADAM zolmitriptan displayed meaningful clinical improvements compared to those treated with placebo.
The FDA accepted a new drug application (NDA) for ADAM zolmitriptan in the acute treatment of migraine in March 2020. The Prescription Drug User Fee Act (PDUFA) date has been set for October 20, 2020.2
“Migraine is a painful and debilitating neurologic disease impacting over 34 million people in the US. The post-hoc analyses suggest that Qtrypta’s efficacy results across approximately 6000 attacks treated in the long-term safety study were consistent with the positive results seen in the pivotal Zotrip study,“ said principal investigator Egilius Spierings, MD, founder and medical director, Medvadis Research Director, Boston Headache Institute, Boston PainCare, in a statement. “I believe that Qtrypta, if approved, has the potential to be a promising and innovative option for migraine patients.”
Over the course of the study, 5617 migraine attacks were observed. Pain freedom at 2 hours was reported for 44% of the migraine headaches treated, while pain relief at 2 hours was reported for 81%. Sustained pain freedom at 2 to 24 hours and 2 to 48 hours was reported for 38% and 35% of the migraine headaches treated, respectively. Sustained pain relief at those same respective time points was reported for 70% and 65% of migraine headaches treated, as well.
As was the case in the pivotal study, the most common adverse events (AEs) observed in the open-label stud were redness and swelling at the application site, of which >95% were classified as mild, and 80% generally resolved within 48 hours. Patients treated with the Zosano agent reported less triptan-like neurological side effects than are typically found with the class, with <2% of patients in the long-term assessment reporting effects such as dizziness and paresthesia.
“As we continue to learn about the profile of our unique investigational product being developed as a potential treatment for headache disorders, we remain committed to sharing this information with the scientific community,” said Don Kellerman, PharmD, vice president, Clinical Development and Medical Affairs, Zosano, in a statement.
The pivotal phase 2/3 study included 321 patients with nausea (n = 110) or severe pain (n = 72) at baseline, those whose treatment was delayed 2 or more hours after onset (n = 75), and those who awoke with migraine (n = 80). Patients had been randomized to either placebo or 3.8-mg zolmitriptan.3,4
For those with nausea, 2-hour pain freedom was achieved in 26 of 59 patients (44%) in the zolmitriptan arm compared to 7 of 51 patients (14%) in the placebo arm (odds ratio [OR], 5.11; 95% CI, 1.96 to 13.30; P = .005), while 2-hour freedom from the most bothersome symptom was achieved in 40 patients (68%) compared to 23 patients (45%), respectively (OR, 2.86; 95% CI, 1.28 to 6.43; P = .009). Meanwhile, 2-hour pain freedom was achieved in 10 of 39 patients who reported severe pain (26%) that were administered zolmitriptan compared to 5 of 33 (15%) of those given placebo (OR, 2.14; 95% CI, 0.60 to 7.62; P = .249). Freedom from the most bothersome symptom at 2 hours was achieved by 25 patients (64%) in the treatment group and 14 patients (42%) in the placebo group (OR, 2.86; 95% CI, 1.05 to 7.79; P = .038).
Among those who awoke with migraine, 16 of 36 patients (44%) and 7 of 44 patients (16%) in the treatment and placebo arms, respectively, were pain‐free at 2 hours (OR, 4.29; 95% CI, 1.50 to 12.31; P = .006). With regard to 2-hour freedom from the most bothersome symptom, the zolmitriptan arm reported freedom in 26 of 36 patients (72%) compared with 17 of 44 patients (39%) in the placebo arm (OR, 4.40; 95% CI, 1.61 to 12.05; P = .003).
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1. Zosano Pharma to showcase new post-hoc analyses of Qtrypta’s (M207) clinical trial data comparing key efficacy results from the pivotal study and the open-label long term safety study on the 2020 American Headache Society’s Virtual Annual Scientific Meeting Platform [press release]. Fremont, CA. Zosano Pharma. Published June 13, 2020. Accessed July 6, 2020. ir.zosanopharma.com/news-releases/news-release-details/zosano-pharma-showcase-new-post-hoc-analyses-qtryptas-m207
2. Zosano Pharma announces FDA acceptance of 505 (b)(2) new drug application for Qtrypta for the acute treatment of migraine [news release]. Fremont, CA. Zosano. Published March 4, 2020. Accessed July 6, 2020. finance.yahoo.com/news/zosano-pharma-announces-fda-acceptance-130010898.html
3. Tepper SJ, Dodick DW, Schmidt PC, Kellerman DJ. Efficacy of ADAM zolmitriptan for the acute treatment of difficult-to-treat migraine headaches. Headache. Published online January 30, 2019. doi: 10.1111/head.13482.
4. Zosano Pharma (ZSAN) Reports Publication of Positive Data on Qtrypta’s Potential as an Acute Treatment for Patients with Difficult-to-Treat Migraines [press release]. Fremont, CA. Zosano Pharma Corporation. Published January 31, 2019. Accessed July 6, 2020. globenewswire.com/news-release/2019/01/31/1708366/0/en/Zosano-Announces-Publication-of-Positive-Data-on-Qtrypta-s-Potential-as-an-Acute-Treatment-for-Patients-with-Difficult-to-Treat-Migraines.html