ALPHA-1062 May Be Substitute for Razadyne: Bioequivalence Study

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by Patricia Inacio, PhD |

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ALPHA-1062, Alpha Cognition’s investigational oral tablet for mild to moderate Alzheimer’s disease, may be a bioequivalent substitute for the approved therapy Razadyne, according to a pivotal trial with healthy volunteers.

The pro-drug therapy — meaning that the medication is metabolized in the body, after administration — showed positive bioequivalence to its reference medication, galantamine hydrobromide immediate release, the scientists said.

Those findings mean that ALPHA-1062 could potentially work to slow the progression of Alzheimer’s symptoms with fewer of the side effects — including nausea, vomiting, and diarrhea — that can occur with Razadyne.

Alpha plans to file a new drug application (NDA) by June 2023 with the U.S. Food and Drug Administration (FDA) seeking the approval of ALPHA-1062, the company said in a press release announcing the results of the bioequivalence study.

“We are very pleased with the positive results from the current studies of our lead asset, ALPHA-1062,” said Cedric O’Gorman, MD, chief medical officer of Alpha Cognition. “If approved, ALPHA-1062 could provide a meaningful advancement for patients with Alzheimer’s disease, especially those who are unable to tolerate the gastrointestinal side effects that often occur with many of the current treatment options.”

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Razadyne, sold by Janssen and available as both immediate-release (IR) and extended-release (ER) tablets, is an approved therapy that slows the progression of symptoms in mild to moderate Alzheimer’s. However, the therapy is known to have gastrointestinal side effects and also can cause insomnia.

ALPHA-1062, designed as a delayed-release tablet, is a pro-drug of galantamine hydrobromide that is metabolized in the body into its active form.

This allows ALPHA-1062 to remain inert while it passes by the stomach, and to be absorbed in the small intestine as an inactive compound. Once it reaches the liver, the active compound — galantamine — is released into circulation, reaching the brain with greater bioavailability.

This mechanism of action reduces the side effects seen with current formulations of galantamine, according to Alpha.

“There is a significant need for innovative new treatment options for patients living with Alzheimer’s disease, as the currently available medicines offer limited symptomatic relief,” said James Galvin, MD, chief of the division of cognitive neurology and director of the Comprehensive Center for Brain Health at the University of Miami, in Florida.

The main goal of the pivotal Bioavailability/Bioequivalence (BABE) study was to investigate ALPHA-1062’s pharmacokinetic equivalence to galantamine hydrobromide. Pharmacokinetics refers to the way the body metabolizes, distributes, and excretes a medication.

To be approved, ALPHA-1062’s effects need to be at least equivalent to galantamine hydrobromide IR. Additionally, the study assessed ALPHA-1062’s safety and tolerability compared with the reference drug.

In the study, 36 healthy individuals were randomly assigned to receive either ALPHA-1062 or galantamine hydrobromide IR. Half received ALPHS-1062 in a single 5 mg dose of ALPHA-1062, while the other 18 were give 4 mg of galantamine hydrobromide IR.

After a seven-day washout period that allowed the effects of the first medication to clear from the body, the participants “crossed over” to the other arm of the study and received the other therapy.

Top-line results showed ALPHA-1062 was bioequivalent to galantamine hydrobromide IR, irrespective of participants being in a fed or fasting status. Also, the results showed that the pharmacokinetic profile of ALPHA-1062 was within the range of that shown for galantamine hydrobromide ER.

Exploratory analyses also revealed no gastrointestinal side effects with ALPHA-1062.

Alpha said it will use the data to seek regulatory approval, with an application to the FDA in the second quarter of next year.

“If approved by the FDA, ALPHA-1062 could provide an exciting next-generation treatment option for patients living with Alzheimer’s disease,” Galvin said.