Alder Reports Positive Top-Line 24-Week Data Demonstrating Persistent Migraine Prevention in Phase 2b Study of ALD403 in Patients with Chronic Migraine
BOTHELL, Wash., July 25, 2016 (GLOBE NEWSWIRE) -- Alder BioPharmaceuticals, Inc. (NASDAQ: ALDR), a clinical-stage biopharmaceutical company developing monoclonal antibody therapeutics, today announced top-line 24-week data demonstrating persistent migraine prevention in a Phase 2b clinical trial evaluating ALD403 in patients with chronic migraine. ALD403 is Alder's proprietary monoclonal antibody product candidate for migraine prevention that targets calcitonin gene-related peptide (CGRP). In March 2016, Alder reported that the Phase 2b study met both the primary efficacy endpoint, a 75% reduction in migraine days over 12 weeks, and the secondary efficacy endpoint of mean reduction in migraine days from baseline.
"The 24-week data confirm and extend our previously reported 12-week data demonstrating robust efficacy in migraine prevention in a severely afflicted patient group. These data will help us finalize the dose selection and design of PROMISE 2, our second planned pivotal trial on track to start later this year," said Randall C. Schatzman, Ph.D., president and chief executive officer of Alder. "Additionally, the data validate the dose selection for the ongoing PROMISE 1 study and further demonstrate ALD403's best-in-class potential as evidenced by prolonged migraine prevention after a single injection. Reinforced by these positive results, we will continue to advance our development plan and, assuming regulatory approval, commercialize ALD403 in the U.S. to meet the needs of the approximate 13 million Americans who are candidates for a migraine preventative therapy."
Key 24-Week Data Points:
- The 24-week data confirm and extend the 12-week data reported previously, including the 75% reduction in migraine days over 12 weeks and the mean reduction in migraine days from baseline, the primary efficacy and secondary endpoints, respectively.
- ALD403 demonstrated a persistent migraine preventative effect:
- The 75% responder rate for the entire 24 weeks at the 300 mg, 100 mg and 30 mg dose levels was 31%, 29% and 30%, respectively, compared to a placebo rate of 20%.
- ALD403 also demonstrated a persistent mean reduction in migraine days from baseline throughout the 24 week period.
- The 10 mg dose continued to be sub-therapeutic. The 10 mg 75% responder rate for the entire 24 week period was 20% compared to the placebo rate of 20%.
- The safety profile was consistent with the 12-week data reported previously and earlier ALD403 clinical trials. There were no new safety findings.
The statistical analysis plan for the Phase 2b trial does not provide for analyses of statistical significance at time points post the primary endpoint at 12 weeks.
Additional results, including future analysis of additional secondary endpoints and other data, are expected to be presented at upcoming medical meetings and published in peer reviewed medical journals. Alder expects that these additional results will further inform the dose selection and design of PROMISE 2.
Endpoints will also be evaluated at week 48, which will mark the end of study.
In March 2016, Alder reported that the 300 mg and 100 mg dose levels met the primary efficacy endpoint of the study, a 75% reduction in migraine days over 12 weeks in 33% and 31% of patients, respectively. A single administration of ALD403 also resulted in an immediate and durable mean reduction in migraine days from baseline throughout the 12 weeks at the 300 mg, 100 mg and 30 mg dose levels, meeting the secondary efficacy endpoint.
The Phase 2b clinical trial is a double-blind, placebo-controlled, randomized, single intravenous infusion, dose-ranging study in patients with chronic migraine. Patients were randomized to receive a single intravenous infusion of 10 mg, 30 mg, 100 mg or 300 mg of ALD403 or placebo (approximately 120 patients per group). The primary efficacy endpoint of the study is the change in migraine days between ALD403 and placebo as determined by the 75% responder rates over a 12-week period. Secondary endpoints include evaluations at week 24 and at week 48 (end of study).
ALD403 is a genetically engineered monoclonal antibody that inhibits calcitonin gene-related peptide, or CGRP, for prevention of migraine. CGRP is a small protein with a well-established role in the initiation, mediation, transmission and heightened sensitivity to pain experienced in migraine. ALD403 was discovered by Alder scientists and has been evaluated in multiple clinical trials evaluating approximately 800 patients. In a proof-of-concept clinical trial evaluating patients with frequent episodic migraine, ALD403 demonstrated significant prevention of migraines, including complete migraine relief (100% suppression of migraine occurrence) in 27% to 41% of patients in any given month. Migraines were completely prevented in 16% of patients for the entire three-month study period. ALD403 also has a favorable emerging safety profile, demonstrating a similar level of safety to placebo, and has been well-tolerated in studies to date.
Migraine is a common neurological disorder that results in suffering caused by intense sharp or throbbing pain in the head, commonly accompanied by nausea, vomiting and high sensitivity to light and sound. Over time, patients may be subject to an increasing frequency and severity of migraine attacks, potentially leading to significant disability.
The Migraine Research Foundation estimates that 36 million American adults and children suffer from migraines. According to the American Migraine Foundation, migraine is three times more common in women than men and affects 30% of women over a lifetime. Migraines can severely restrict normal activities and often make holding a job or maintaining a normal lifestyle difficult. The Migraine Research Foundation estimates U.S. employers lose more than $13 billion each year as a result of 113 million lost work days due to migraine.
Currently, preventive medications approved for migraine include beta blockers (such as propranolol), topiramate, sodium valproate and botulinum toxin, or Botox. Medication side-effects, such as cognitive impairment, nausea, fatigue and sleep disturbance, often limit the use of migraine medications, according to the American Migraine Foundation. The U.S. Agency for Healthcare Research and Quality reports that only about 12% of adults with frequent episodic or chronic migraine take preventive medications. Alder believes this creates a significant unmet medical need for new treatments with improved safety and efficacy that can either prevent migraines completely or reduce the frequency to a level where patients can find adequate relief from existing abortive medications.
About Alder BioPharmaceuticals, Inc.
Alder BioPharmaceuticals, Inc., is a clinical-stage biopharmaceutical company that discovers, develops and seeks to commercialize therapeutic antibodies with the potential to meaningfully transform current treatment paradigms. ALD403, Alder's lead pivotal-stage product candidate being evaluated for migraine prevention, is a genetically engineered monoclonal antibody that inhibits calcitonin gene-related peptide. Alder's second program, ALD1613, targets adrenocorticotropic hormone and is intended for the treatment of congenital adrenal hyperplasia and Cushing's disease. Clazakizumab, Alder's third program, is a monoclonal antibody candidate designed to block interleukin-6 and is licensed to Vitaeris, Inc. For more information, please visit http://www.alderbio.com.
This press release contains forward-looking statements, including, without limitation, statements relating to: the continued development and clinical, therapeutic and commercial potential of ALD403; the initiation of future clinical trials and studies; future regulatory filings and the anticipated commercialization of ALD403; the availability, future analysis and presentation of clinical trial data; and the need for new migraine treatments. Words such as "help," "selection," "design," "planned," "confirm," "extend," "will," "on track," "validate," "demonstrate," "potential," "continue," "advance," "commercialize," "expected," "inform," "believes," "need," "intended," or other similar expressions, identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. The forward-looking statements in this press release are based upon Alder's current plans, assumptions, beliefs, expectations, estimates and projections, and involve substantial risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements due to these risks and uncertainties as well as other factors, which include, without limitation: risks related to the potential failure of ALD403 to demonstrate safety and efficacy in clinical testing; Alder's ability to conduct clinical trials of ALD403 sufficient to achieve a positive completion; the availability of data at the expected times; the clinical, therapeutic and commercial value of ALD403; risks and uncertainties related to regulatory application, review and approval processes and Alder's compliance with applicable legal and regulatory requirements; the uncertain timing and level of expenses associated with the development of ALD403; the sufficiency of Alder's capital and other resources; market competition; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Alder's Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on April 28, 2016, and is available on the SEC's website at www.sec.gov. Additional information will also be set forth in Alder's other reports and filings it will make with the SEC from time to time. The forward-looking statements made in this press release speak only as of the date of this press release. Alder expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Alder's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.