The possible addition of a new lithium-based drug to the list of available therapeutics is important because many physicians are reluctant to prescribe lithium.
Alzamend Neuro’s AL001 could be an effective replacement for current lithium carbonate treatments for patients with Alzheimer’s disease, bipolar disorder or other neurological conditions, based upon results from a just-completed Phase I trial. Now the company is planning to launch a Phase IIa multiple ascending dose study in patients with mild to moderate Alzheimer’s. To that point, Alzamend recently contracted with Altasciences Clinical Kansas to manage the study, and iResearch Atlanta to conduct it.
AL001, a lithium-engineered crystal delivery system, is being developed as a lithium dose-sparing replacement for the current lithium carbonate-approved treatment of patients with bipolar disorder, and for novel lithium treatment indications including Alzheimer’s disease, major depressive disorder and post-traumatic stress disorder (PTSD).
Data showed AL001 is bioequivalent in plasma to a marketed lithium carbonate product currently used to treat bipolar disorder. That research also noted that lithium plasma concentration over time curves for AL001 and lithium carbonate are similar. Human clinical trials are planned to confirm rodent studies showing that lithium dosing requirements can be lowered because of greater AL001 lithium brain penetration/persistence.
Simply put, “It can have greater bioavailability where it needs to be, in the brain, and be less of a burden to other body organs, resulting in less toxicity risk,” Stephan Jackman, CEO of Alzamend, told BioSpace. “We’re looking forward to getting into the clinic for Phase II multiple ascending dose (‘MAD”) studies this quarter,” he added.
Lithium is a well-known treatment in this space. One of the most recent studies of its effectiveness was published in late March in PloS Medicine. In it, researchers from the University of Cambridge reported that lithium can reduce the risk of developing dementia both short-term and long-term. The study consisted of a retrospective analysis of the health records of almost 30,000 people with a mean age of 73.9 years, between 2005 and 2019.
The possible addition of a new lithium-based drug to the list of available therapeutics is important because many physicians are reluctant to prescribe lithium.
“Lithium can be toxic if not carefully dosed. Patients receiving lithium treatments should have their blood monitored for lithium levels routinely,” Jackman pointed out. However, more than 3 million people in the U.S. are prescribed lithium and some 40 million potentially could benefit.
“Our formulation is able to reach blood lithium levels within the same safe range as currently marketed lithium salts, but we anticipate that AL001 will require lower lithium doses than lithium salts to provide adequate therapeutic brain levels,” he said. “This may reduce or avoid the need for lithium therapeutic drug monitoring.”
To make it easier for Alzheimer’s patients (in particular) to take this medication, Jackman said, “We’ve created a sprinkle capsule that can be opened and sprinkled into coffee or tea, for example, because it’s often hard for them to swallow pills.”
Although some biopharma companies begin talking with payers and patient advocates quite early, Jackman plans to begin this process once Phase II is completed. “We believe patients, advocates and payers will be very happy to have something that has a better safety profile than the current therapy,” he said.
Given the well-documented effects of lithium, it appears that AL001 treatment can also be applied to multiple other neurodegenerative and neurologic disorders.
“We are developing an investigational new drug application (IND) for bipolar disorder,” he continued. Because the lithium in AL001 was demonstrated to be bioequivalent in plasma to lithium carbonate, evidence regarding safety can be bridged to the marketed products, and the company can focus on Phase IIb efficacy studies.
Later this year, Alzamend also plans to file INDs for major depressive disorder and post-traumatic stress disorder (PTSD).
While its lithium therapeutic may be furthest along, Alzamend is also developing a more novel approach to treat - and even reverse - Alzheimer’s disease using an autologous dendritic cell therapy that is based on a vaccine platform. It’s called AL002.
“This isn’t an immunotherapeutic,” Jackman emphasized. “We’re treating Alzheimer’s disease as if the rogue proteins that cause it need to be removed by the patient’s own immune system. Therefore, we’re looking to take the patient’s own blood, spin out the dendritic cells, mix them with a mutant peptide, and create a vaccine that then goes back into the patient to help remove these undesirable proteins. This use of a specialized mutant protein should minimize side effects.
“More specifically, AL002 triggers a targeted immune response throughout the body, and appears promising in terms of eliminating oligomer amyloid beta plaque, which is considered to be heavily involved in causing Alzheimer’s disease,” Jackman said. AL002 can be administered intradermally and intravenously to harness the human body’s own defenses against plaque buildup in the brain.
In mouse models, this therapeutic vaccine reversed the effects of Alzheimer’s disease and restored cognition. The question, however, is whether it could do that in humans. Alzamend plans to submit the IND for a Phase I/II trial this quarter.
