Umibecestat

A shot of a senior man sitting on the sofa with his daughter, looking at a photograph. He is cuddling his daughter, looking sad and holding the photo. SolStock/Getty Images June is Alzheimer’s & Brain Awareness Month and June 21 is dubbed “The Longest Day,” which focuses on raising awareness of Alzheimer’s disease. June is Alzheimer’s & Brain Awareness Month and June 21 is dubbed “The Longest Day,” which focuses on raising awarenes s of Alzheimer’s disease. As most everyone knows, Alzheimer’s is a common form of dementia. In the U.S., it affects about 5.7 million people. Without any cure, it is estimated that by 2050, 14 million Americans will be living with the disease. The U.S. is expected to spend $277 billion on Alzheimer’s or other dementia care this year alone. Baby boomers, if a treatment isn’t developed, will push that number to $1.1 trillion by 2050. Unfortunately, so far, drug development for Alzheimer’s disease has been a barren wasteland of failed clinical trials. By at least one report, more than 190 Alzheimer drugs have failed in clinical trials. Recent failures include vTv Therapeutics ’ Phase III trial for azeliragon, which failed to meet primary endpoints; AstraZeneca and Eli Lilly ’s lanabecestat, which was abandoned this month; Johnson & Johnson ’s Janssen division ended its trials of atabacestat in May; and in February, Merck & Co . announced it was halting protocol 019, its APECS Phase III clinical trial of verubecestat (MK-8931). In a statement in June, Eli Lilly’s president of Lilly Research Labs, Daniel Skovronsky, said in a statement, “The complexity of Alzheimer’s disease poses one of the most difficult medical challenges of our time, and we are deeply disappointed for the millions suffering from this devastating disease.” In late January, Pfizer announced it was abandoning its research and development of new neuroscience programs and cutting eight different projects, of which four early-stage programs were for Alzheimer’s. But in June, the company threw another $600 million into its venture capital fund, with a quarter earmarked for neuroscience research investments. Although it seems grim, hopefully, it will turn out to be like Thomas Edison’s adage about inventing the light bulb, which was, “I have not failed. I’ve just found 10,000 ways that won’t work.” With any luck, biopharma won’t require 10,000 failures. With that in mind, here’s a look at some of the ongoing Phase III clinical trials in Alzheimer’s disease. The Alzheimer’s Association keeps tabs on ongoing trials, breaking them down to treatment trials, diagnostic studies, prevention trials, quality of life studies, and online studies. Those studies are broken down further into phases. In April, the association listed 15 ongoing Phase III trials for Alzheimer’s, with about another 27 for related symptoms. Unfortunately, some listed include those already terminated. However, here’s a look at some of the ongoing Phase III trials for Alzheimer’s disease. Biogen ’s aducanumab. Aducanumab is one of the top prospects for Alzheimer’s disease, although not without its skeptics. It is currently in a Phase III trial. The company sent tremors through its stock value in February when the company’s chief medical officer, Al Sandrock, speaking at the Leerink Healthcare Conference, said Biogen had added 510 more patients to the trial because, he said, “We did see more variability on the primary endpoint than assumed when we did the initial sample size estimations. So we decided to increase the sample size to maintain 90 percent power.” A lot of investors viewed that as the company said it wasn’t getting the results it expected, so was increasing its sample size. Originally some data was going to be presented at the end of the year, but it seems more likely in 2020, with possibly some interim data being released here and there before then. Aducanumab is an antibody that targets beta-amyloid, the plaques that build up in the brains of Alzheimer’s patients and is the primary theory behind the damage caused to cognition. Novartis and Amgen’s CAD-106 and CNP520. In September 2015, Novartis and Amgen entered into a global collaboration to commercialize and develop neuroscience treatments. One was a BACE inhibitor program for Alzheimer’s disease. BACE is involved in the development of beta-amyloid. CAD106 is designed as a vaccine against beta-amyloid. It is composed of a short piece of beta-amyloid that includes only the amino acids 1 to 6. The idea is it will trigger an immune response to prevent new plaques from forming. The study also is looking at CNP520 from Amgen. CNP520 is a BASE inhibitor. The study launched in October 2015 and is expected to run until at least 2020, and probably to 2023. Roche/Genentech’s crenezumab. Genentech announced in February 2017 that it was launching a second Phase III trial of crenezumab with its partner AC Immune . The CREAD2 trial will recruit 750 patients with prodromal or mild Alzheimer’s. Crenezumab is also an antibody against beta-amyloid. In a statement at the time, Andrea Pfeifer, the chief executive officer of AC Immune, said, “Given the recent disappointing results of other therapies, all of us in the Alzheimer’s community need to redouble our efforts to combat one of society’s biggest challenges. We remain confident about the potential of crenezumab given it is distinct from other beta amyloid antibodies, predominantly blocking oligomers in the brain, and has a clinical development program that is using higher dosing and targeting earlier stages of Alzheimer’s disease.” Biogen and Eisai’s elenbecestat. On June 4, the two companies announce d that in a Phase II clinical trial, the BACE inhibitor was found to be generally safe and well tolerated. It also showed a statistically significant difference in amyloid beta levels in the brain of patients as measured by amyloid-PET scans. There was also a possible delay of clinical symptoms. The trial involved 70 patients with mild cognitive impairment due to Alzheimer’s or mild to moderate dementia due to Alzheimer’s with confirmed amyloid pathology by PET scans. They were randomized to four treatment arms of elebecestat, 5, 15, or 50 mg, or placebo. The two companies are currently running two global Phase III clinical trials of the drug in early Alzheimer’s disease. “It is highly encouraging that Study 202 confirmed elenbecestat’s treatment effect in reducing amyloid in the brain and suggested a slowing of clinical decline,” said Lynn Kramer, chief clinical officer and chief medical officer, Neurology Business Group, Eisai, in a statement. “Eisai and Biogen will continue to work together to advance the ongoing Phase III program (MISSION AD) in order to contribute a new potential treatment option to Alzheimer’s disease patients as soon as possible.” Although there is no guarantee any of these trials will be the trial that breaks through with a new Alzheimer’s drug approval, many companies are continuing to learn more and more about the disease and test new approaches to treatment and prevention.

Novartis announced they have expanded their collaboration with the Banner Alzheimer’s Institute to launch a new clinical trial in ALZ’s. Amgen and Basel, Switzerland-based Novartis announced they have expanded their collaboration with the Banner Alzheimer’s Institute (BAI) to launch a new clinical trial in Alzheimer’s. The trial is called the Alzheimer’s Prevention Initiatives (API) Generation Study 2, which will follow the launch of the Generation Study 1. It will evaluate whether CNP520, a BACE1 inhibitor, can prevent or delay onset of Alzheimer’s disease symptoms in a high-risk population. The Generation Study 2 began enrolling patients in the U.S. in August. It is planned to include more than 180 locations in more than 20 countries. The study will last five years and include approximately 2,000 cognitively health participants. Their ages are 60-75 and based on genetic tests, carry either two copies of the apolipoprotein E (APOE) 4 gene or one copy of the gene with evidence of increased brain amyloid. The Generation Study 1 only targets people with two copies of APOE4. APOE4 is a major genetic risk factor for late-onset Alzheimer’s disease. About 25 percent of people carry a single copy of the APOE4 gene, but only around two percent of the population worldwide carries two copies. Participants in the studies will receive either a placebo or one of two doses of CNP520. The drug was co-developed by Amgen and Novartis. “As a leader in the challenging fight to unlock the biology of serious illnesses like Alzheimer’s disease, we are pleased to support the launch of the Generation Study 2 with our partners at Novartis and Banner Alzheimer’s Institute to further explore promising potential therapeutic options for this highly debilitating disease,” said Sean Harper, Amgen’s executive vice president of Research and Development, in a statement. “Through the unique combination of genetic testing and counseling in cognitively healthy adults, the Generation Study 2 exhibits an innovative clinical approach that may offer insight towards Alzheimer’s prevention for those at highest risk for developing the disease.” One of the key theories behind Alzheimer’s disease is the accumulation of amyloid-beta plaques in the brain. BACE1 is an enzyme that has a role in the production of amyloid-beta. The Alzheimer’s Prevention Initiative (API) is an international collaborative research program led by the Banner Alzheimer’s Institute. It conducts trials in cognitively healthy people at high-risk of Alzheimer’s with a focus on prevention. Part of the initiative is the establishment of brain imaging, biological and cognitive measurements to test promising prevention treatments and to assist registries in enrollment for future prevention trials. The two companies, Amgen and Novartis, launched their Neuroscience Collaboration in 2016, with the intention to develop and commercialize therapies in the field of migraine and Alzheimer’s disease. In migraine, that includes Amgen’s Aimovig (erenumab), whose Biologics License Application was accepted by the U.S. Food and Drug Administration (FDA) in July 2017, and AMG 301, which is currently in Phase I trials. In April 2017, the collaboration expanded to include co-commercialization of Aimovig in the U.S. Amgen retains exclusive rights to commercialize drugs other than Aimovig in the migraine program in the U.S. and Japan, and Novartis has exclusive commercialization rights in Europe, Canada and the rest of the world. The two companies are also collaborating on a BACE inhibitor program in Alzheimer’s disease.