FREMONT, Calif., Sept. 13, 2017 (GLOBE NEWSWIRE) — Zosano Pharma Corp. (NASDAQ:ZSAN) (“Zosano” or the “Company”) a clinical-stage biopharmaceutical company focused on providing rapid systemic administration of therapeutics to patients using our proprietary ADAM technology, presented data from its pivotal Phase 2/3 ZOTRIP study evaluating M207 as an acute treatment for migraine during the 18th Annual Congress of the International Headache Society in Vancouver, BC. The data were presented by Dr. Don Kellerman, Vice President of Clinical Development and Medical Affairs.
As previously reported, the 3.8mg dose of M207 met both co-primary endpoints of pain freedom and most bothersome symptom freedom at 2 hours. In addition, the 3.8mg dose showed durability of effect on pain freedom to 24 and 48 hours.
Two other poster presentations related to the results of the ZOTRIP study were presented at the meeting. Dr. Pete Schmidt and co-authors presented an abstract entitled “Experience with Delayed Treatment of Migraine and Morning Migraine Treatment Using Intracutaneous Zolmitriptan (M207).” Dr. David Dodick and co-authors presented a poster based on an abstract entitled “Use of Most Bothersome Symptom as an Endpoint in an Acute Treatment of Migraine Trial.”
M207 is designed to rapidly deliver zolmitriptan during a migraine attack utilizing Zosano’s proprietary Adhesive Dermally-Applied Microarray, or ADAM technology. Zosano’s ADAM technology consists of titanium microprojections coated with drug, and in the case of M207, our formulation of zolmitriptan. Our ADAM technology delivers zolmitriptan by abrading the stratum corneum and allowing drug to be absorbed into the microcapillary system of the skin.
“Presenting our results in a rigorous scientific forum, and discussing them with world-class headache experts is very valuable for helping us understand the types of patients who might benefit most from our unique drug delivery method,” said Dr. Kellerman. “We continue to receive positive input from experts in the field about how this product could be valuable in the treatment paradigm for migraine, once it is available for patients. We have been fortunate to work with a great group of Clinical Advisors who continue to provide valuable insight as we move forward with clinical development.”
Zosano’s novel delivery of zolmitriptan was confirmed by the results from the ZOTRIP study, where 41.5% of the patients treated with the 3.8mg dose of M207 achieved pain freedom at 2 hours, and the effect also appeared to be durable, with 31.7% and 26.8% of patients achieving sustained pain freedom from 2-24 hours and 2-48 hours respectively. In post-hoc analyses, M207 also demonstrated efficacy in traditionally difficult to treat established migraine headaches, as evidenced by a nearly identical therapeutic effect in those who treated prior to and after 2 hours. Additionally, 44 % of patients who awoke with their migraine headache were pain-free at 2 hours. Patients in this trial were instructed not to treat until their headache reached moderate to severe intensity and the mean time from headache onset to treatment was almost 5 hours.
The ZOTRIP Study
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.
Five hundred and eighty nine subjects were enrolled in this study, of which 365 were randomized. Of those randomized, 333 subjects treated and are included in the safety analysis, and 321 qualified for the modified intent-to-treat (mITT) population. 51% of the subjects randomized were found to have severe migraine pain pre-treatment. Also at the time of treatment, 70% reported nausea, 37% aura, and 51% waking up with their migraine (morning migraine). With the multiple doses and multiple endpoints in the trial, a sequential testing procedure was used beginning with the highest dose and the co-primary endpoints. Since statistical significance was not achieved for most bothersome symptom in the 1.9 mg group, p-values for secondary endpoints should be considered nominal p-values.
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|
|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.
Migraine is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation. Migraine symptoms can include moderate to severe headache pain combined with nausea and vomiting, or abnormal sensitivity to light and sound. According to the Migraine Research Foundation, migraine affects 30 million men, women and children in the United States. Most migraines last between four and 24 hours, but some last as long as three days. According to published studies, 63% of migraine patients experience between one and four migraines per month. According to Decision Resources, prescription drug sales for migraine in the top seven countries were estimated to be $3.3 billion in 2015, and are expected to grow to $4.4 billion in 2020. Triptans, a family of tryptamine-based drugs first sold in the 1990s, account for almost 75% of anti-migraine therapies prescribed at office visits.
M207 is our proprietary formulation of zolmitriptan delivered utilizing Zosano’s proprietary Adhesive Dermally-Applied Microarray, or ADAM technology. Zosano’s ADAM technology consists of titanium microprojections coated with drug, and in the case of M207, our formulation of zolmitriptan. Our ADAM technology delivers drug by abrading the stratum corneum and allowing drug to be absorbed into the microcapillary system of the skin. In February 2017, the Company announced statistically significant results from the ZOTRIP trial, which demonstrated that the 3.8mg dose of M207 met both co-primary endpoints, achieving pain freedom and most bothersome symptom freedom at 2 hours.
About Zosano Pharma
Zosano Pharma Corporation is a clinical stage biopharmaceutical company focused on providing rapid systemic administration of therapeutics to patients using our proprietary Adhesive Dermally-Applied Microarray, or ADAM technology. The Company recently announced positive results from our ZOTRIP study that evaluated M207, which is our proprietary formulation of zolmitriptan delivered via our ADAM technology, as an acute treatment for migraine. Zosano is focused on developing products where rapid administration of established molecules with known safety and efficacy profiles provides an increased benefit to patients, for markets where patients remain underserved by existing therapies. The Company anticipates that many of its current and future development programs may enable the Company to utilize a regulatory pathway that would streamline clinical development and accelerate the path towards commercialization. Learn more at www.zosanopharma.com.
This press release contains forward-looking statements regarding the timing of expected clinical development milestones, sufficiency of our capital resources and need for future funding and other future events and expectations. Readers are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “might,” “believes,” “estimates,” “projects,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “forecast,” “designed,” “goal,” “unaudited,” “approximately” or the negative of those words or other comparable words to be uncertain and forward-looking. These statements are subject to risks and uncertainties that are difficult to predict and actual outcomes may differ materially. These include risks and uncertainties, without limitation, associated with the process of discovering, developing and commercializing products that are safe and effective for use as human therapeutics, risks inherent in the effort to build a business around such products and other risks and uncertainties described under the heading “Risk Factors” in the Company’s most recent annual report on Form 10-K.. Although we believe that the expectations reflected in these forward-looking statements are reasonable, we cannot in any way guarantee that the future results, level of activity, performance or events and circumstances reflected in forward-looking statements will be achieved or occur. All forward-looking statements are based on information currently available to Zosano and Zosano assumes no obligation to update any such forward-looking statements.
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