Alpha Cognition’s Oral Therapy Receives FDA Approval to Treat Alzheimer's Disease

Alpha Cognition recently announced the US FDA has granted approval for ZUNVEYL (benzgalantamine), previously known as ALPHA-1062, for the treatment of mild-to-moderate Alzheimer’s disease. Alzheimer’s disease (AD) is a progressive brain disorder that slowly destroys memory, thinking skills, and eventually the ability to do simple tasks, like carry on a conversation. AD is the most common form of dementia affecting nearly 7 million people, and is the leading cause of nursing home admissions and deaths, with 70% of all nursing home residents suffering with AD.

A novel oral therapy, ZUNVEYL has a dual mechanism of action designed to eliminate drug absorption in the GI tract, potentially addressing certain tolerability issues with leading AD medications, combined with the efficacy and long-term benefit profile of galantamine. Tolerability affects therapy adherence, with data showing that 55% of AD patients discontinue their medication after one year, mainly due to GI side effects and insomnia. Medication discontinuation can cause risk to patients themselves, and dissatisfaction and burden among nursing home staff, physicians, and caregivers.

ZUNVEYL, a prodrug of AD treatment galantamine and an acetylcholinesterase inhibitor (AChEI), is postulated to exert its therapeutic effect by preventing the breakdown of acetylcholine, the important brain neurotransmitter involved in memory, motivation, and attention functions. It is also an allosteric potentiator of α-7 nicotinic acetylcholine and α4β2 receptors. This action facilitates the release of acetylcholine from the presynaptic neurons, giving clinical significance to its dual mode of action. ZUNVEYL targets AD symptoms, to provide patients with long-lasting benefits to cognitive and global function and the ability to perform daily activities that are impaired by AD. Galantamine, FDA-approved since 2001, has extensive and positive data related to long-term outcomes, demonstrating activity among multiple brain receptors, anti-inflammatory effects, and is associated with improved memory, attention, and a significantly lower risk of death. It also has the strongest effect on cognitive decline in the AChEI class of medications and demonstrated significant risk reduction of developing severe dementia. Due to its prodrug properties, ZUNVEYL is effectively converted into the active moiety of galantamine after it passes through the GI tract, therefore achieving the same therapeutic effects of galantamine. It was also uniquely designed to eliminate drug absorption in the GI tract, potentially addressing certain tolerability issues and has a CNS safety profile that includes no incidence of insomnia. Information about ZUNVEYL’s pivotal clinical studies are included further in this press release, and in the ZUNVEYL prescribing information.

“I am very excited about the approval of ZUNVEYL, which we believe offers better tolerability for patients with Alzheimer’s disease. We have always believed in the efficacy of galantamine but have been limited in its use due to tolerability issues. To now have an agent with the efficacy of galantamine, but that also offers the hope of better tolerability, will provide physicians a great option to treat patients,” said Elaine Peskind, MD, the Friends of Alzheimer’s Research Professor of Psychiatry at the University of Washington School of Medicine. “This advancement marks a meaningful step forward in improving the quality of life for those living with Alzheimer’s and their families. As a geriatric psychiatrist specializing in Alzheimer’s disease, I am eager to incorporate this new treatment into our practice and see the positive difference it will make.”

“The approval of ZUNVEYL is a pivotal moment in the fight against Alzheimer’s disease as it is only the second oral AD treatment to be approved in more than a decade. ZUNVEYL was designed to addresses a critical need for a tolerable and effective treatment that can potentially enhance patients’ daily lives with improved long-term outcomes,” added Alpha Cognition Chief Executive Officer Michael McFadden. “We are delighted, as this represents a major breakthrough in Alzheimer’s treatment, providing hope to millions of patients, families, and caregivers affected by this devastating disease.”

ZUNVEYL’s approval was based on chemistry, manufacturing, and controls information and data demonstrating the bioequivalence and tolerability of ZUNVEYL compared to galantamine immediate-release tablets and galantamine extended-release capsules. Importantly, there were minimal adverse events reported in these trials.

Efficacy, Tolerability, Safety: The efficacy of ZUNVEYL is based upon 3 bioavailability studies in healthy adults comparing galantamine immediate-release tablets and galantamine extended-release capsules to ZUNVEYL. GI adverse events documented across all studies for ZUNVEYL were less than 2% and no insomnia was observed.

Dual Mechanism of Action: While precise mechanism of action is not known, it is believed that ZUNVEYL works through two distinct pathways to enhance neurotransmitter activity and protect neuronal health, leading to improved cognitive and functional outcomes.

Long-Term Benefits: Clinical trials for galantamine (ZUNVEYL’s active moiety) have demonstrated sustained improvements in cognitive function and quality of life over extended periods of treatment.

ZUNVEYL will be available by prescription in pharmacies nationwide in Q1 2025. Alpha Cognition is committed to ensuring broad access to this innovative treatment and will work closely with healthcare providers, insurers, and patient advocacy groups to support its distribution.

“We are excited to launch ZUNVEYL and bring this much-needed treatment option to patients suffering from Alzheimer’s disease,” said Lauren D’Angelo, Alpha Cognition’s Chief Operating Officer. “Over the coming months, our team will work diligently to prepare for this launch, ensuring that healthcare providers have the information and patients have the resources and support they need. ZUNVEYL offers dual-action benefits with the established efficacy of galantamine and no insomnia. It was uniquely designed to bypass the gut with the potential of minimizing GI side effects. We believe that ZUNVEYL’s unique combination of these attributes will make a meaningful difference in the lives of those affected by this debilitating disease. We look forward to collaborating with our partners to ensure a successful rollout and broad accessibility.”

Alpha Cognition Inc. is a clinical stage, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (mTBI), for which there are currently no approved treatment options.

ZUNVEYL, previously ALPHA-1062, is a novel patented oral Alzheimer’s disease therapy with a dual mechanism of action designed to eliminate drug absorption in the GI tract, potentially addressing certain tolerability issues with leading AD medications, combined with the efficacy and long-term benefit profile of galantamine. As a new generation acetylcholinesterase inhibitor, it was developed to demonstrate a potentially improved GI side effect profile and has a CNS safety profile that includes no incidence of insomnia. While precise mechanism of action is not known, it is believed that ZUNVEYL works through two distinct pathways to enhance neurotransmitter activity and protect neuronal health, leading to improved cognitive and functional outcomes.

Separately, ZUNVEYL is also being developed in combination with memantine to treat moderate-to-severe Alzheimer’s dementia, and as an intranasal formulation for Cognitive Impairment with mTBI. For more information about ZUNVEYL, visit www.zunveyl.com or contact info@alphacognition.com and connect with us on Twitter and LinkedIn.