Next-Generation Lithium Product for PTSD Treatment Seeks to Proceed to Phase 2 Study

Alzamend Neuro, Inc. today announced that it has submitted an investigational new drug ("IND") application to the U.S. Food and Drug Administration ("FDA") for the initiation of AL001-PTSD01, a Phase IIA plasma/brain pharmacokinetics clinical study of AL001, for treatment of patients with post-traumatic stress disorder (PTSD).

After receipt of a "study may proceed" communication from the FDA, Alzamend plans to initiate a Phase IIA study to characterize AL001 improvements of lithium levels in the brain compared to a marketed lithium salt in PTSD patients.

Alzamend anticipates that the new drug application ("NDA") development program for PTSD may, for safety, qualify for a 505(b)(2) NDA pathway to FDA approval, which can be available to new formulations of an approved drug.

"There are only two drugs approved by the FDA and currently available in generic form for PTSD patients," said Stephan Jackman, Chief Executive Officer of Alzamend, in a press release on November 13, 2023.

"Being able to develop a next-generation lithium product (AL001) that would not routinely require therapeutic drug monitoring (TDM) could positively impact the 9 million Americans afflicted with PTSD."

"We look forward to providing more details regarding the study's timeline and market opportunity in the near future."

Although lithium products do not have an FDA-approved indication for PTSD, case reports suggest that lithium treatment may be useful for treating PTSD patients. In particular, treatment with low doses (300–600 mg/day) of lithium carbonate has been reported to provide effective treatment in the reduction of inappropriate anger, irritability, anxiety, and insomnia in those patients.

The clinical observation of mood swings beyond the normal range, but milder than those associated with BD, reportedly suggested the presence of a sub-threshold mood disorder in these PTSD patients.

It has also been proposed that treatment of trauma with lithium to forestall the development of PTSD may be provided by pharmacological induction of mild transient amnesia.

Lithium was the first mood stabilizer approved by the FDA and is still a first-line treatment option for BD but is underutilized, perhaps because of the need for TDM, that is, routine monitoring of lithium drug levels in blood to help assure safety and effectiveness.

Lithium was the first drug that required TDM by regulatory authorities in product labeling because the effective and safe range of therapeutic drug blood concentrations is narrow and well-defined for treating BD when using lithium salts. Excursions above this range can be toxic, and below can impair effectiveness.

AL001 is a novel lithium-delivery system that has the potential to provide the benefits of marketed lithium salts while mitigating or avoiding currently experienced toxicities associated with lithium.

Results from Alzamend's recently completed Phase IIA multiple-ascending dose study of AL001 in Alzheimer's patients and healthy subjects identified a maximum tolerated dose ("MTD") that an independent safety review committee vetted.

This MTD is designed to distribute more lithium to the brain but at lower systemic exposure, resulting in an improved safety profile compared to currently marketed lithium salts.

This MTD was assessed to be unlikely to require TDM.

PTSD is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats to a person's life.

According to the NIH, about 3.6%, or roughly 9 million, adults in the U.S. have PTSD in a given year, and 9% of people develop it at some point in their life.

Children may also experience very stressful events that affect their thoughts and feelings.

In much of the world, rates for a given year are between 0.5% and 1% of the population.

As of November 13, 2023, the FDA has not approved an Alzheimer's disease-related vaccine candidate.

NOte: On Dec. 11, 2023, the headline was updated.