Data from Phase 3 trials of tramiprosate (ALZ-801) suggest that the therapy might be modifying the disease course in patients with mild Alzheimer’s disease and two copies of the APOE4 gene, the drug’s developer, Alzheon, recently announced.
With data in hand, the Framingham, Massachusetts, company plans to further clinical development of the compound. But for now, Alzheon will use a precision medicine approach, including only patients with these characteristics in an additional Phase 3 trial.
The findings, published in The Journal of the Prevention of Alzheimer’s Disease, showed that patients with mild Alzheimer’s experienced a stabilization of cognitive and functional capacities to a larger degree than a combined group of patients with both mild and moderately severe Alzheimer’s.
The study, “Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer’s Disease Suggest Disease Modification Potential,” also suggested that effects on cognition increased significantly with time.
“We are now seeing a convergence of new insights on how amyloid-targeted therapies can be optimized to treat Alzheimer’s disease patients,” Dr. Jeffrey Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said in a press release.
“A new understanding of amyloid pathogenesis has evolved from the recent studies on the molecular mechanism of tramiprosate,” he added. “These observations better position us to develop new therapies for Alzheimer’s and to choose populations most likely to respond to treatment.”
The study built on new analyses of data from two Phase 3 clinical trials (NCT00088673 and NCT00217763) of the drug, which involved patients with mild to moderate Alzheimer’s disease. An earlier analysis of the trials revealed that patients carrying APOE4 mutations seemed to benefit more from the treatment. Those with two gene copies benefitted the most.
This suggests that tramiprosate might be a suitable candidate for a precision medicine approach, in which only select patients are likely to experience a treatment effect.
“Our published results in JPAD represent the culmination of research efforts at Alzheon in which we have ‘connected the dots’ for directing our anti-amyloid treatment to the patient population most likely to benefit,” said Dr. Martin Tolar, Alzheon’s founder, president and CEO.
The recent development has allowed Alzheon to move forward with its clinical development of tramiprosate.
“Alzheon has defined a new, highly targeted path for developing innovative medicines for Alzheimer’s, such as ALZ-801, by directing treatment to the right patients, with the right drug, and at the right stage of their disease,” said Tolar.
Although Alzheon helped patients with mild Alzheimer’s more, the drug’s safety profile was similar among various groups in the trial. The most common adverse events among tramiprosate-treated patients were nausea, vomiting, depression and weight loss.
“ALZ-801 represents a new class of oral agents with disease-modifying potential, and based on our clinical analyses and discovery of the molecular mechanism of action, we have defined the patient selection criteria for the upcoming confirmatory study of ALZ-801 in homozygous APOE4/4 patients with Mild AD,” said Dr. Susan Abushakra, the company’s chief medical officer.
“With these promising efficacy data, the favorable long-term safety profile of tramiprosate, and the improved gastrointestinal tolerability of ALZ-801, we are poised to initiate the pivotal program with ALZ-801 for patients in need of effective treatment,” she said.
Alzheon has not yet said when its new Phase 3 trial will launch.