Alder Also Reports Positive Phase 1 Data Supporting Quarterly Single Injection Dosing Strategy for ALD403
Alder to Host Conference Call at 8:30 a.m. Eastern Time Today
Alder BioPharmaceuticals, Inc. (ALDR), today announced positive top-line data from two clinical trials evaluating ALD403, Alder’s proprietary monoclonal antibody product candidate for migraine prevention that targets calcitonin gene-related peptide (CGRP). Positive top-line data from a Phase 2b study of patients with chronic migraine demonstrated that ALD403 acted rapidly and prevented migraine over the entire 12 week study period, meeting both primary and secondary efficacy endpoints. Additionally, positive Phase 1 study data demonstrated that the pharmacokinetics and pharmacodynamics by intravenous (IV), subcutaneous (SC) or intramuscular (IM) injection of ALD403 support a quarterly single injection dosing strategy.
Randall C. Schatzman, Ph.D., president and chief executive officer of Alder, commented: “Today’s ALD403 Phase 2b data confirm and expand on our previous data demonstrating robust efficacy in migraine prevention in a severely afflicted patient group. Evaluation of ALD403 continues to exhibit a potential best-in-class profile, which includes immediate, significant and durable migraine prevention with infrequent quarterly dosing. Today’s data also support our quarterly dosing strategy via a single intravenous, subcutaneous or intramuscular injection. With our commitment to the accelerated development of ALD403 reinforced by today’s positive results, we look forward to advancing our development plan, and assuming FDA approval, independently marketing ALD403 in the U.S. to meet the critical medical needs of the 13 million patients nationwide who are candidates for migraine prevention therapy.”
Phase 2b Clinical Trial Evaluating ALD403 in Patients with Chronic Migraine
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. Endpoints will also be evaluated at week 24 (expected Q3 2016) and at week 48 (end of study).
Chronic migraine sufferers are defined as individuals who experience 15 or more headache days per month, of which at least 8 must be assessed as migraine days.
- The 300 mg and 100 mg dose levels of ALD403 met the primary efficacy endpoint of the study, a 75% reduction in migraine days over the entire 12 weeks in 33% and 31% of patients, respectively (p < 0.05).
|% Reduction in
|300 mg IV
|100 mg IV
|30 mg IV
|10 mg IV
|Weeks 1-12||50||%||65 (57%)**||64 (54%)*||64 (55%)*||54 (44%)||47 (41%)|
|75||%||38 (33%)*||37 (31%)*||33 (28%)||33 (27%)||24 (21%)|
|100||%||9 (8%)||6 (5%)||5 (4%)||10 (8%)||3 (3%)|
*(p= < 0.05) **(p= < 0.01)
- A single administration of ALD403 resulted in an immediate and durable mean reduction in migraine days from baseline throughout the 12 weeks at the 300 mg (p < 0.01), 100 mg (p < 0.01) and 30 mg (p < 0.05) dose levels, meeting the secondary efficacy endpoint.
- A single administration of ALD403 at 300mg, 100mg or 30mg dose levels demonstrated a durable reduction in migraine days for the entire 12 weeks, supporting a quarterly dosing strategy.
- The 10 mg dose of ALD403 was identified as sub-therapeutic.
- The safety profile was consistent with earlier ALD403 clinical trials.
Phase 1 Clinical Trial Evaluating Multiple Doses of ALD403 in Healthy Volunteers
The Phase 1 clinical trial is a placebo-controlled, randomized, multi-dose, double dummy, quarterly-dosing study comparing the intravenous, subcutaneous and intramuscular routes of administration in healthy volunteers. Sixty healthy volunteers, 12 in each group, were randomized as follows:
• 100 mg ALD403 IM, placebo SC, placebo IV
• 100 mg ALD403 SC, placebo IM, placebo IV
• 100 mg ALD403 IV, placebo IM, placebo SC
• 300 mg ALD403 IM, placebo SC, placebo IV
• Placebo IM, placebo SC, placebo IV
Individuals were dosed on Day 1 and at Week 12.
The study evaluated pharmacokinetic and pharmacodynamic endpoints for the administration of ALD403 delivered via each of the three routes of administration.
- ALD403 provided a comparable level of suppression of peripheral CGRP biology for a full 3 months when administered via a single intravenous (100 mg), subcutaneous (100 mg) or intramuscular injection (100 mg or 300 mg).
- ALD403 administered via subcutaneous or intramuscular routes of administration had an approximately 80% bioavailability relative to an intravenous infusion.
- Local tolerability via all modes of administration was excellent.
- The safety profile was consistent with earlier ALD403 clinical trials.
- The data support a quarterly dosing strategy as a single injection by all modes of administration.
The results of this study provide an important bridge between pharmacodynamic monitoring via peripheral CGRP blockade and migraine prevention: doses (100mg and 300mg) that provided for a full 3 months of migraine prevention in the Phase 2b study of chronic migraine patients also provided 3 months of suppression of peripheral CGRP biology independent of route of administration.
Additional results, including future analysis of additional secondary endpoints, from both of these trials are expected to be presented at upcoming medical meetings and published in peer-reviewed medical journals.
Conference Call and Webcast
Alder will host a conference call at 8:30 a.m. ET today to discuss these clinical trial results. The live call may be accessed by dialing 877-430-4657 for domestic callers or 484-756-4339 for international callers and by providing conference ID number 80096426.
A simultaneous webcast with slides will be broadcast live on the investors section of Alder’s website at www.alderbio.com and will be available for replay following the call for 30 days.
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. Alder initiated its late-stage clinical trial program in October 2015 with PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 1 (PROMISE 1), a pivotal clinical trial evaluating patients with frequent episodic migraine. Alder plans to initiate a second pivotal clinical trial,PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 2 (PROMISE 2), in patients with chronic migraine in the second half of 2016. Also in 2016, Alder further plans to enter late-stage clinical development of a self-injected formulation of ALD403 to complement the infusion formulations evaluated in the PROMISE 1 and 2 trials.
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
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 (CGRP). CGRP is a small protein with a well-established role in the initiation, transmission and heightened sensitivity to migraine pain. Alder’s second program, ALD1613, targets adrenocorticotropic hormone (ACTH) and is intended for the treatment of Congenital Adrenal Hyperplasia or Cushing’s disease. ALD1613 is undergoing Investigational New Drug (IND)-enabling preclinical studies and an IND submission is planned for 2016. Additionally, Alder’s clazakizumab, is designed to block the pro-inflammatory cytokine IL-6 and has completed two successful Phase 2b clinical trials. Alder is seeking strategic opportunities for clazakizumab. 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, ALD1613 and clazakizumab; the availability of clinical trial data; future regulatory filings and the anticipated commercialization of ALD403; the initiation of future clinical trials and studies; and the pursuit of strategic alternatives for clazakizumab. Words such as “support,” “continues,” “potential,” “strategy,” “commitment,” “look forward,” “seeking,” “advancing,” “marketing,” “expected,” “plans,” “initiate,” “further,” “enter,” “believes,” “submit,” “intended,” “designed,” or other similar words or expressions, identify forward-looking statements, but the absence of these words or expressions 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, ALD1613 and clazakizumab to demonstrate safety and efficacy in clinical testing; the availability of data at the expected times; the clinical, therapeutic and commercial value of ALD403, ALD1613 and clazakizumab; risks and uncertainties related to regulatory 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, ALD1613 and clazakizumab; 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2015, which was filed with the Securities and Exchange Commission (SEC) on February 23, 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 makes 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.