EnVivo Pharmaceuticals has announced positive results from phase II b clinical trial of EVP-6124, a novel alpha-7 agonist, in patients with Alzheimer’s disease. The results were presented at the Alzheimer's Association International Conference 2012 (AAIC) being held in Vancouver, British Columbia.

The six-month, double-blind phase II b clinical trial evaluated EVP-6124 against placebo in patients with mild to moderate Alzheimer’s disease. The EVP-6124 2.0 mg dose met both of the trial’s primary endpoints with statistically significant positive effects on cognition (p=0.0189), as measured by the Alzheimer's Disease Assessment Scale-Cognitive subscale-13 (ADAS-Cog-13) and clinical function (p=0.0253) as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). The data also showed statistically significant results across secondary endpoints of other cognitive and clinical measures. Importantly, EVP-6124 was generally safe and well-tolerated over the trial’s six-month dosing period. Based on the phase II b trial results, EnVivo will continue to advance EVP-6124 and plans to initiate a phase III clinical trial in Alzheimer’s disease in 2013.

“One in eight Americans over the age of 65, or approximately five million people, currently have Alzheimer’s disease, and combined with the aging baby boomer generation that number is expected to triple by 2030,” said Jeffrey L Cummings, MD, Sc.D., director of the Cleveland Clinic Lou Ruvo Centre for Brain Health in Las Vegas and Cleveland, and the Andrea and Joseph Hahn Chair of Neurotherapeutics of the Neurological Institute of Cleveland Clinic. “Despite extensive R&D efforts and a broad range of approaches taken by researchers and biotech and pharmaceutical companies over the past several decades, progress has been slow, the effectiveness of our current standard of care is limited and the patient need is critical. These data are compelling for the physician community and encouraging for patients and their families, and I am looking forward to learning more about how EVP-6124 may provide a new treatment option as it is further evaluated.”

“These positive data presented today mark an encouraging milestone for Alzheimer’s patients and for EnVivo,” said Kees Been, president and chief executive officer of EnVivo Pharmaceuticals. “The results position us to advance the EVP-6124 program to have the greatest possible impact on the greatest number of patients. With these positive phase IIb data in hand, EnVivo has taken another step to potentially commercialize EVP-6124 and translate our promising research into a fully integrated biotechnology company with full commercial and R&D capabilities.”

The six-month, double-blind, placebo-controlled study enrolled 409 patients and evaluated three doses of EVP-6124 taken once per day - 0.3 mg, 1.0 mg and 2.0 mg - against placebo. The trial included patients taking acetylcholinesterase inhibitor (AChEI) treatments (donepezil and rivastigmine) as well as patients not taking AChEIs. The 2.0 mg dose group showed statistically significant effects for both of the trial’s primary endpoints compared to placebo after 23 weeks of dosing. Patients on the 2.0 mg dose saw an improvement in cognition (not just maintenance of current cognitive function) over the 23 weeks of dosing and were still separating from the placebo group at the end of the trial, as assessed by the ADAS-Cog-13, a commonly used outcome measure and established clinical endpoint (p=0.0189) for cognition. Patients on the 2.0 mg dose also saw a positive effect on clinical function, as assessed by the CDR-SB, a clinical rating scale that assesses patient function (p=0.0253).

The 2.0 mg dose group demonstrated statistically significant cognition improvements across pre-defined secondary endpoints compared to placebo after 23 weeks of dosing, including the cognition composite (p=0.0037), memory composite (p=0.0088) and executive function composite (p=0.0427). The 2.0 mg group also showed positive effects versus placebo, as measured by the Mini-Mental State Examination (MMSE) (p=0.0955), and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (p=0.092). The 0.3 mg and 1.0 mg doses showed positive trends, but not statistically significant improvements over placebo. EVP-6124 was generally safe and well-tolerated with some mild to moderate gastrointestinal side effects reported in a minority of patients in both the 1.0 mg and 2.0 mg dose groups.

“These data continue to support our understanding of EVP-6124’s novel mechanism and its development as a potential treatment for Alzheimer’s disease and schizophrenia,” said Dana Hilt, MD, senior vice president, clinical development and chief medical officer of EnVivo. “In all of the studies we’ve conducted evaluating EVP-6124 to-date, we have seen pro-cognitive dose-dependent effects and we believe the novel mechanism has the potential to alleviate the undesirable side effects caused by other systemic compounds – for example, acetylcholinesterase inhibitors – which are dose-limited by side effects. We are extremely pleased with these results and look forward to initiating a phase III trial next year.”

Alzheimer’s disease is a complex neurodegenerative disease that affects the brain. One in eight Americans over the age of 65, or approximately five million people, currently have Alzheimer’s disease, and with the aging of the baby boomer generation, the total number is expected to nearly triple by 2030. Alzheimer's disease is the sixth-leading cause of death in the United States. Over time, the disease destroys large areas of the brain resulting in cellular loss and dysfunction, a gradual loss of memory, problems with reasoning or judgment, disorientation, difficulty in learning, loss of language skills, and decline in the ability to perform routine tasks. People with Alzheimer’s disease can also experience changes in their personalities and behavioral problems, such as agitation, anxiety, delusions and hallucinations.

EnVivo Pharmaceuticals’ lead compound, EVP-6124, is a selective, potent, brain penetrant, oral alpha-7 nicotinic agonist being developed as a long-term treatment to restore and improve cognitive function with sustained effect in Alzheimer’s disease and schizophrenia. EVP-6124 offers a novel mechanism of action by enhancing synaptic transmission in the brain and acting as a co-agonist in combination with Acetylcholine (ACh) to enhance cognition. By sensitizing the alpha-7 receptor, EVP-6124 makes it possible for smaller amounts of naturally occurring ACh to be effective in activating the A7 receptor. This mechanism of action could potentially alleviate the undesirable side effects caused by other systemic compounds (for example, acetylcholinesterase inhibitors, or AChEIs), which are dose-limited by toxic side effects. EVP-6124 has also been shown to increase the levels of key neurotransmitters such as glutamate and dopamine in key brain areas, which may be linked to enhanced cognition, not only in Alzheimer’s disease and schizophrenia, but in other diseases.

EnVivo announced positive topline data from its double-blind, placebo-controlled phase II b clinical trial of EVP-6124 in schizophrenia in May 2011 and presented a comprehensive analysis of these findings in December 2011. Results demonstrated that EVP-6124 produced statistically significant and clinically meaningful effects on both cognition and functional symptoms, including global cognitive function, clinical function and negative symptoms. Building upon these findings, EnVivo is planning to advance the program into phase III clinical trials in 2012 with a primary focus on improving cognition in schizophrenia patients.