ATLANTA– Alzamend Neuro, Inc. (Nasdaq: ALZN) (“Alzamend”), an early clinical-stage biopharmaceutical company focused on developing novel products for the treatment of neurodegenerative diseases and psychiatric disorders, today announced that the first patient with mild to moderate Alzheimer’s disease (“Alzheimer’s”) has been dosed in a 12-month Phase IIA multiple ascending dose (“MAD”) study for dementia related to Alzheimer’s. The MAD study is for the purpose of evaluating the safety and tolerability of AL001 under multiple-dose, steady-state conditions and determining the maximum tolerated dose in patients diagnosed with mild to moderate Alzheimer’s. AL001 is a novel lithium-delivery system; it is a lithium-salicylate-L-proline engineered ionic cocrystal under development as an oral treatment for patients with dementia related to mild, moderate, and severe cognitive impairment associated with Alzheimer’s. AL001 has the potential to deliver benefits of marketed lithium carbonate while mitigating or avoiding current toxicities associated with lithium.
“Advancing AL001 into a Phase IIA clinical trial as planned marks an important milestone for Alzamend,” said Stephan Jackman, Chief Executive Officer of Alzamend. “We are one step closer to proving that AL001 could potentially provide clinicians with a major improvement over current lithium-based treatments and may constitute a means of treating over 40 million Americans suffering from Alzheimer’s and other neurodegenerative diseases and psychiatric disorders. We look forward to completing the MAD study and further advancing clinical development of this promising potential therapeutic.”
The Phase IIA study will evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions and determine the maximum tolerated dose in patients diagnosed with mild to moderate Alzheimer’s. Lithium has been well characterized for safety and is approved/marketed in multiple formulations for bipolar affective disorders. Lithium dosing for the MAD cohorts is based on a fraction of the usual dose for treatment of bipolar affective disorder (i.e., AL001 lithium content at a lithium carbonate equivalent of 300 mg 3-times daily (“TID”), daily total of 900 mg), with the target dose for Alzheimer’s treatment at half of that lithium carbonate equivalent value (150 mg TID, daily total of 450 mg). In each cohort, consisting of 6 active and 2 placebo patients (as per randomization), multiple ascending doses will be administered TID for 14 days under fasted conditions (at least 1 hour before or 4 hours after meals) up to tolerability/safety limits. The lithium and salicylate components of AL001 will be given within the amounts already approved for use in patients. Up to 40 subjects will complete the Phase IIA trial. The maximum tolerated dose will then be used for further studies.
During this Phase I trial, participants received a single dose of AL001 containing lithium in an amount equivalent to 150 mg lithium carbonate, a dose proposed as likely appropriate for Alzheimer’s treatment when given TID. Currently, marketed lithium carbonate 300 mg capsules are given TID when prescribed for manic episodes in bipolar disorder as well as for maintenance therapy of bipolar disorder in patients with a history of manic episodes. It can be difficult to control the appropriate dose of lithium salt formulations, including lithium carbonate, due to the small margin between effective and toxic blood levels, and therefore it can be challenging to avoid side effects or inadequate treatment outcomes.
The data affirmed that dose-adjusted relative bioavailability analyses of the rate and extent of lithium absorption in plasma indicate that AL001 at 150 mg lithium carbonate equivalent dosage is bioequivalent when dose-normalized to the marketed 300 mg lithium carbonate product and the shapes of the lithium plasma concentration versus time curves are similar. Based on the Phase I results, it has been shown that dose-normalized systemic bioequivalence for lithium was established between AL001 and the marketed reference lithium carbonate 300 mg capsule. Findings of plasma bioequivalence to a marketed lithium product may allow Alzamend to reduce the scope or eliminate the need for Phase II and III studies of efficacy and/or safety of AL001 in such indications as bipolar affective disorders in which lithium efficacy has been established. Demonstrated bioequivalence also may have utility for AL001 when seeking approval for new indications as a benchmark for safety.
