Zosano Announces Publication Of Pivotal Data Of ADAM Zolmitriptan For The Acute Treatment Of Migraine In Cephalalgia
FREMONT, Calif., Oct. 12, 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 subjects using its proprietary Adhesive Dermally-Applied Microarray (“ADAM”) technology, announced today that Cephalalgia had published the Company’s positive results from our pivotal, multi-center, double blind, placebo controlled, trial demonstrating efficacy and safety of M207, our formulation of zolmitriptan using our ADAM technology.
ADAM is Zosano Pharma’s proprietary, investigational technology platform designed to offer rapid drug absorption into the bloodstream, which can result in an improved pharmacokinetic profile compared to original dosage forms. ADAM consists of an array of drug-coated titanium microprojections mounted on an adhesive backing that is pressed on to the skin using a reusable handheld applicator. The microprojections penetrate the stratum corneum and allow drug to be absorbed into the microcapillary system of the blood.
Cephalalgia published a paper titled “Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center Study of the Safety and Efficacy of ADAM Zolmitriptan for the Acute Treatment of Migraine”, which contained the positive results from Zosano’s ZOTRIP pivotal study. ZOTRIP 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. In this study of 365 migraineurs, the 3.8mg dose of M207 demonstrated a statistically significant benefit in both freedom from pain and freedom from a patient’s most bothersome symptom (photophobia, phonophobia or nausea and vomiting) at the 2 hour pre-specified primary endpoint. Secondary endpoints demonstrated pain freedom at 45 min after administration, with an effect that was sustainable for 48 hours post treatment. The majority of adverse events were mild or moderate application site reactions. There were no serious adverse events. Zosano announced the results of the ZOTRIP trial in February 2017.
“We are grateful for the contributions of our investigators, co-authors and advisors on the design, execution, analysis and reporting of the ZOTRIP trial,” said Dr. Don Kellerman, Vice President of Clinical Development. “We believe that the time from topline results to peer-reviewed publication in a prestigious journal reflects the design of the study and the unambiguous results.”
"We are pleased to have the results of ZOTRIP, our pivotal study, published in Cephalalgia," stated John P. Walker, Zosano’s Chairman and Chief Executive Officer. "The recognition of the results from ZOTRIP in such a well-known journal will continue to raise awareness of M207, and its ability to address an unmet need for patients struggling to find rapid and durable pain relief for migraine episodes.”
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.
Chief Business Officer and
Chief Financial Officer