Encenicline Hydrochloride

September 15, 2015 By Mark Terry , BioSpace.com Breaking News Staff The U.S. Food and Drug Administration (FDA) advised Waltham, Mass.-based FORUM Pharmaceuticals to halt its clinical trials of encenicline for Alzheimer’s disease yesterday. The FDA cited a small number of serious gastrointestinal (GI) side effects in the studies. As a result, FORUM halted the trial, discontinuing the medication and no new patients will be recruited until the clinical hold is lifted. The company is working with the FDA on a plan to continue the study. In addition, the FDA told the company that a trial in cognitive impairment in schizophrenia (CIS) has also been placed on a clinical hold. Two fully enrolled Phase III efficacy trials, however, that are evaluating encenicline to treat CIS will continue. In June 2015, FORUM received Fast Track designation for encenicline to treat CIS from the FDA . Encenicline is an oral, highly brain-penetrant, selective agonist of the alpha 7 receptor that is found in hippocampal and cortical neurons involved in cognition, in other words, brain cells involved in thinking. FORUM believes the drug activates alpha 7 receptors to increase its response to a naturally occurring neurotransmitter called acetylcholine. This, in turn, is believed to activate brain networks related to sensory gating, attention and cognition. A number of companies are working on Alzheimer’s medications, although it’s a difficult area with far more failures than successes. Swiss-based Roche reported in Dec. 2014 that it was discontinuing Scarlet RoAD, a Phase III study of gantenerumab on pre-dementia Alzheimer’s disease. In March 2015 Biogen, Inc. showed positive results of its Alzheimer’s drug, aducanumab. Another Roche drug, in an agreement with Germany-based Evotec , announced in July that its Phase IIb clinical trial of sembragiline in Alzheimer’s failed to meet its primary endoint. Eli Lilly and Company presented positive results for its Alzheimer’s drug, solanezumab, which had previously shown disappointing clinical trials in 2012. The company has shifted its focus to a subgroup of AD patients with a mild form of the disease that responded to the drug. A 2014 report in Alzheimer’s Research UK indicated that 244 Alzheimer’s drugs were tested between 2002 and 2012, and only one was approved, Lundbeck A/S ’s Ebixa. Even the few that are approved and on the market aren’t considered to be terribly effective. The biggest AD drug on the market is Eisai Company, Ltd. ’s Aracept. Others are Exelon, by Novartis , Razadyne by Janssen , and Namenda, by Actavis . Jeffrey Holford , an analyst with Jefferies and Co. , predicted that if the Lilly drug was approved, it could hit annual sales of more than $3 billion globally. In June 2015 Axovant Sciences Ltd. , which focuses on Alzheimer’s drugs, went public , raising $315 million overnight, the largest deal ever for a pre-revenue biotech company. The company’s product, RVT-101, which it bought from GlaxoSmithKline for $5 million and milestone payments, has shown some success in alleviating AD symptoms, but did not prevent the disease from progressing. Mark Schoenebaum , a biotech analyst who leads the biotech team at ISI Evercore , wrote an investor note in May that tries to pin down the size of the AD drug market. “There are 600,000 mild AD patients in the U.S.,” he wrote. “At a net price of around $20,000 (below TNFs), 65 percent penetration would yield a potential sales opportunity of around $8 billion in the U.S. alone. The ex-U.S. patient opportunity is similar, but price would probably be lower.”

WATERTOWN, Mass., May 11 /PRNewswire/ -- EnVivo Pharmaceuticals today announced the initiation and dosing of patients in a Phase IIb study of its EVP-6124 compound, a selective alpha-7 nicotinic agonist in patients with mild to moderate Alzheimer's disease. The multi-center, dose ranging, placebo controlled, six-month study taking place in the U.S. and Europe is designed to determine the safety and efficacy of EVP-6124 in producing procognitive effects and improving the clinical condition of Alzheimer's disease patients. "Patients with Alzheimer's disease have a number of symptomatic therapies available to them. However, the effects of the available medications are modest. Even if significant progress is made in slowing disease progression, more effective therapies that sustainably improve the cognition of the patients are clearly needed," said Kees Been, EnVivo president and CEO. "There is growing consensus that alpha-7 nicotinic agonists can potentially improve the cognitive function in Alzheimer's disease patients as evidenced by the number of large pharmaceutical companies advancing similar drugs through development. The potential upside for patients is considerable and we look forward to completing our Alzheimer's disease study by the middle of next year." The Phase IIb study will enroll mild to moderate Alzheimer's disease patients who will be randomized to three separate doses of EVP-6124 or placebo over six months. Efficacy will primarily be determined by the ADAS-Cog scale, a commonly used and accepted measure of cognition in patients with Alzheimer's disease. Secondary assessments will include other cognitive and clinical measures. EVP-6124 also is being tested in patients with schizophrenia in a separate Phase IIb study that started in late 2009. Two previous studies with EVP-6124 in Alzheimer's disease patients demonstrated that it was well tolerated and produced significant effects on a variety of cognitive measures of brain function such as attention, memory and executive function (complex thinking tasks). EVP-6124 had procognitive effects in two separate clinical trials: one study conducted in Alzheimer's disease patients already treated with Acetyl Choline Esterase Inhibitors (AChEI) and one in Alzheimer's disease patients not on AChEI therapy (naive patients). EVP-6124 is a selective agonist for the alpha-7 subtype of the nicotinic acetylcholine receptor and is being developed by EnVivo for potential cognitive enhancement in both schizophrenia and Alzheimer's patients. It has been shown to have excellent CNS penetration, oral bioavailability, pharmacokinetics and metabolic profile. About EnVivo Pharmaceuticals EnVivo Pharmaceuticals, located in Watertown, Mass., is a biopharmaceutical company dedicated to discovering and developing small molecule therapeutics for disorders of the central nervous system, with a current focus on Alzheimer's disease, cognitive disorders and schizophrenia. The company's lead product is an alpha-7 nicotinic acetylcholine receptor agonist and has been tested in Phase IIa clinical trials for cognition disorders in Alzheimer's disease and schizophrenia. The company's other programs include an epigenetics program based on Histone Deacetylase inhibition (HDACi) with EVP-0334 as the lead molecule for cognition in Alzheimer's disease which has completed Phase I studies, and several preclinical programs such as a Gamma Secretase Modulator (for Alzheimer's disease) and a PDE10 inhibitor program (for schizophrenia). For more information about EnVivo, visit . SOURCE EnVivo Pharmaceuticals