EnVivo Pharmaceuticals Presents Positive Comprehensive Phase 2b Study Results in Schizophrenia at American College of Neuropsychopharmacology Annual Meeting
Data Featured in ACNP "Hot Topics" Session; EVP-6124 Shows Statistically Significant Improvement in Cognition, Function and Impact on Negative Symptoms
WATERTOWN, Mass. and WAIKALOA BEACH, Hawaii, December 5, 2011 - EnVivo Pharmaceuticals, a company dedicated to developing a broad range of novel central nervous system (CNS) therapies, announced today that it is presenting the comprehensive analysis of a recently completed Phase 2b clinical trial of EVP-6124, a novel, orally bioavailable nicotinic alpha-7 agonist, in schizophrenia at the American College of Neuropsychopharmacology 50th Anniversary Annual Meeting. Data were discussed as part of the meeting's "Hot Topics" invited panel session on Sunday, December 4 and will be presented in two posters today, Monday, December 5.
Results presented at ACNP show EVP-6124's statistically significant and clinically meaningful effects on both cognition and functional symptoms, including global cognitive function, the Phase 2b trial's pre-specified primary endpoint, as measured by the CogState computerized battery. Building upon these findings, EnVivo is planning to advance the program into Phase 3 clinical trials in 2012 with a primary focus on improving cognition in schizophrenia patients.
"Almost all schizophrenia patients suffer from debilitating functional impairment, due in large part to cognitive or negative symptoms, for which there are no currently approved treatments," said Herbert Y. Meltzer, M.D., Ph.D., professor in psychiatry and behavioral sciences at the Northwestern University Feinberg School of Medicine and an investigator in the Phase 2b trial. "As a clinician, I know that patients and their families are suffering due to the current lack of effective and tolerable treatments for these two key components of the syndrome. These encouraging data further support EVP-6124's potential as a novel approach that could improve cognitive function and decrease the negative symptoms of schizophrenia, thereby having a dramatic impact on the way schizophrenia is treated and on patients' quality of life."
Dana Hilt, M.D., senior vice president, clinical development and chief medical officer of EnVivo, presented the Phase 2b data as part of the ACNP "Hot Topics" session along with Dr. Meltzer. The comprehensive findings show that:
EVP-6124 demonstrated a statistically significant effect on global cognitive function, the trial's pre-specified primary endpoint as measured by the CogState battery, for all EVP-6124 treated patients versus placebo (p=0.05), with the most effective dose being 0.3 mg (p=0.009). While not statistically significant, the 1.0 mg dose showed a positive trend on computerized CogState testing and also showed a positive effect on the paper-and-pencil MATRICS Consensus Cognitive Battery (MCCB) test.
Significant effects in the secondary endpoint of clinical function also were seen with EVP-6124 treatment as measured by the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Rating. The 1.0 mg dose group showed a statistically significant improvement (p=0.011) over placebo after three months of dosing.
Improvement was also seen in the secondary endpoint assessing negative symptoms of schizophrenia as measured by the Positive and Negative Symptoms Scale (PANSS). The 1.0 mg dose group showed a statistically significant decrease in negative symptoms (p=0.028) compared to the placebo group after three months of dosing with the 0.3 mg group also demonstrating a positive trend.
EVP-6124 was well tolerated over three months of dosing, with an excellent safety and tolerability profile - the most commonly reported adverse events were headache, nausea and nosopharyngitis (all less than four percent), there were no drug-related serious adverse events and more adverse events were reported in the placebo group than in the EVP-6124 treated groups.
"Our Phase 2b trial was an important clinical success as we saw statistically significant improvements in all pre-specified endpoints including cognitive function and negative symptoms and have learned more about our potential optimal dose," said Dr. Hilt. "We are encouraged by the results across both dose arms and the broad range of primary and secondary endpoints. We are now working with leading clinicians and researchers to finalize the design of our Phase 3 trials to maximize these learnings and most efficiently and effectively evaluate EVP-6124 in schizophrenia patients who have significant unmet medical needs."
"These findings represent a significant advance in the development of a novel, safe and effective treatment for schizophrenia," said Kees Been, president and chief executive officer of EnVivo Pharmaceuticals. "This clinical ‘proof of concept' in humans is an important milestone for any drug candidate and was a pivotal event for EnVivo. We expect to move into Phase 3 development with a focus on the cognitive symptoms of schizophrenia next year. We also look forward to sharing updates from our current ongoing Phase 2b clinical trial of EVP-6124 in patients with Alzheimer's disease in the first half of 2012."
Today, EnVivo and Dr. Meltzer also will present two posters at ACNP. The first will highlight the Phase 2b data previously discussed during the "Hot Topics" session. The second will outline findings in a preclinical pharmacology model that show that EVP-6124 acts as a co-agonist and sensitizes the alpha-7 receptor, enhancing cognition and memory and also increases the release of dopamine, acetylcholine and glutamate.
Schizophrenia is a psychiatric disorder that affects approximately 2.4 million Americans, or about one percent of the adult population, and is usually diagnosed between the ages of 15 and 35 years old. Symptoms of schizophrenia include positive and negative symptoms as well as cognitive impairment. "Positive" symptoms include hallucinations, delusions and paranoia. "Negative" symptoms include loss of motivation and interest in everyday activities, blunting of emotion, decrease in speech and social withdrawal. Increasingly, cognitive impairments such as difficulty paying attention, memory loss and problems processing information and making decisions are also recognized as core disabling symptoms of the disease. The overall annual cost of schizophrenia in the U.S. is more than $62 billion according to a study published in the Journal of Clinical Psychiatry.
About the EVP-6124 Phase 2b Clinical Trial
This Phase 2b trial evaluated the safety and efficacy of two doses of EVP-6124 (0.3 mg and 1.0 mg per day) versus placebo in chronic schizophrenia patients on stable second-generation antipsychotic drugs (except clozapine). Each patient was treated for three months and a total of 319 patients were enrolled in the U.S., Russia, Ukraine and Serbia. The trial's primary endpoint was overall cognition as measured by the CogState overall cognitive index and important secondary endpoints included cognition as assessed by the MCCB battery, clinical function (as measured by the SCoRS) and positive and negative symptoms (measured by PANSS). Safety and tolerability were also assessed.
The lead compound in EnVivo's alpha-7 agonist program, EVP-6124, is a selective, potent, brain penetrant oral compound that offers a novel mechanism of action - it enhances synaptic transmission in the brain and acts 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 could potentially alleviate the undesirable side effects caused by other systemic compounds (for example, Acetylcholinesterase inhibitors- AChE-Is), which are dose-limited by toxic side effects.
About EnVivo Pharmaceuticals
EnVivo Pharmaceuticals, Inc. and its subsidiaries ("EnVivo Pharmaceuticals" or "EnVivo") are dedicated to discovering and developing small molecule therapeutics for disorders of the central nervous system (CNS). EnVivo Pharmaceuticals, Inc. is a biotech company located in Watertown, Mass. The company's focus is on building an integrated company and it is working to convert its broad pipeline into a range of CNS therapies that leverage novel mechanisms of action by altering the progression of disease and providing improvement in cognitive and overall function. EnVivo's lead product is an alpha-7 nicotinic acetylcholine receptor agonist that has successfully completed a Phase 2b clinical trial in schizophrenia and is currently in an ongoing Phase 2b clinical trial for the treatment of cognitive impairment in Alzheimer's disease. EnVivo's other programs include an epigenetics program based on Histone Deacetylase inhibition (HDACi) in preparation for Phase 2 studies, a Gamma Secretase Modulator program in Phase 1 and several preclinical programs including a potent and selective PDE10 inhibitor program expected to enter the clinic in early 2012. For more information about EnVivo, visit www.envivopharma.com.