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(CNN) – After a series of major failures, there are reasons to hope in the search for a drug to slow the progression of Alzheimer's disease. The results of an early trial of an experimental drug showed that it improves cognition and reduces the clinical signs of Alzheimer's in the brain of study participants, and the Experts are "cautiously optimistic" that the results will be replicated in future clinical trials. , an antibody called BAN2401, not only reduces the formation of new amyloid beta clusters in the brain, but reduces existing clusters by an average of 70%, US biogenetic company Biogen and Japanese drug maker Eisai said on Wednesday. The accumulation of beta-amyloid in the brain is a hallmark of Alzheimer's disease.
BAN2401 also provided a 26% to 30% advantage over a placebo in improving cognition in study subjects, according to the researchers. Details on immunotherapy were presented at a press conference at the International Conference of Alzheimer's in Chicago in 2018.
"These are people with mild alterations, a some confusion, forgetting the name of someone on the occasion "clinical and medical doctor for Eisai. "It's the goal: to stop Alzheimer's disease when it's in the sweetest presentation."
The reaction of the experts was mixed. "I would not say shock and admiration," said Dr. Julie Schneider, professor of pathology at Rush Medical College. "It is encouraging to see a cognitive effect and slow the progression of the disease, but I personally think that there is still a lot of work to be done."
Maria Carrillo, scientific leader of the nonprofit Alzheimer's Association. "Is the future, and there will be no bullet to defeat the Alzheimer's disease, so being able to delay the progression of the disease for a few years would be huge."
Dr. Richard Isaacson, who runs the Alzheimer's Disease Prevention Clinic at the New York-Presbyterian Medical Center / Weill Cornell, said the research is "impressive on the surface, but we need to be cautiously optimistic. These data may be encouraging, but it is not possible to say with certainty. I do not want us to be wrong again, "as with previous failed trials.
BAN2401 is administered intravenously and has been tested in five badays in 856 patients with mild or severe cognitive impairment. from an early stage of Alzheimer's disease. Phase two trial, which evaluates the dosage of a drug.
Hoping that the drug would be a viable treatment had decreased in December when participants failed to show significant improvement by the first goal of the 12-month study.However, Biogen recently stated that the highest dose of 10 milligrams per kilogram of body weight, administered every two weeks, showed a statistically significant success at the end of the 18-month study.
Kramer said that Eisai and Biogen had contacted the US, Europe and Japan regulators to say to share results and next steps. The company said it hoped to obtain accelerated approval.
"This was only a phase two trial, and it will not be approved by the Food and Drug Administration until the results of the next largest trial are over," said Keith Fargo, director of programs scientists at the Alzheimer's Association. "Accelerated approval simply means that you are going ahead instead of behind the line."
For patients anxiously waiting for help, Fargo warned it will be several years before the drug is available.
"You will not be able to go to the doctor and you will receive it anytime soon," Fargo said.
Safety and Side Effects
Previous safety trials have shown that BAN2401 was well tolerated at all levels, including much lower rates of a well-deserved side effect. Known anti-amyloid treatment: Microblocking and minor swelling of the brain called abnormalities of amyloid imaging, or ARIA-E.
Kramer said that less than 10% of patients in any of the five arms have experienced an ARIA, which can create headaches, confusion and visual disturbances that disappear once the drug stopped.
"Of the 48 cases of ARIA-E, only five were symptomatic," said Kramer, "and could only be identified with an MRI, of which only one couple had external symptoms."
Patients with an ApoE gene ε4, the leading genetic risk factor for Alzheimer's disease, are more susceptible to ARIA-E problems. For safety reasons, said Kramer, an organism Regulatory outside the United States asked researchers to remove most of the patients with the high-dose beneficial group gene who received injections twice a month.However, they left patients with ApoE ε4 in the placebo arm of the study.
According to Isaacson, this may have created a major flaw in the research.
"ApoE ε4 patients decline faster," he said. "L & # Was the study so good because it placed all the Is ApoE ε4 in the placebo arm, or has the study been good because lowering of the amlyoid improves cognitive function? It's the confusing part. "
Isaacson says that clinical doctors who see patients with ARIA-E who are also ApoE ε4-positive recommend that they stay in a high-dose group, because the side effects are often manageable. [19659002] "Regulators must enter the same room as the researchers and agree on things so that these confusing changes do not happen midway through," he said. "In my opinion, there is no reason to do that."
The Amyloid Hypothesis
BAN2401 is one of many potential drugs using "The Amyloid Hypothesis", a belief that getting rid of beta-amyloid is expected to improve memory loss and other cognitive changes seen in Alzheimer's. Various drug makers have targeted beta amyloid while trying to 39, stop training, train the immune system to kill him or remove it from the blood and brain.
Results to date have been poor. By the end of 2016, Eli Lilly's solanezumab failed to outweigh the benefits of placebo in a Phase III trial of 2100 patients. In 2013, Pfizer discarded another antibody, bapineuzumab, when it did not outperform placebo effects in another phase III trial. Experts suggest that advanced stages of Alzheimer's disease among participants in both trials might have contributed to the failures.
The pharmaceutical giant Merck has used a different approach to fight against beta-amyloid in people with advanced Alzheimer's with its BACE inhibitor. In early 2017, after an independent study, he concluded that he had "virtually no chance" of working. A second attempt to treat the early stages of Alzehimer was also dropped in February.
The atabecestat, a Johnson & Johnson BACE inhibitor, designed to slow cognitive decline in people at risk for Alzheimer's, was also discontinued in May when hepatic enzymes boosted participants.
One of the possible reasons for the success of BAN2401. is that the trial was among the first to use PET scanners to verify that every participant in the study had definite signs of beta amyloid in their brain. Older studies eventually revealed that a number of patients tested did not actually have the aggregates and plaques targeted, which could explain failure rates.
The other Biogen amyloid antibody, aducanumab, also uses the PET scan model in its tests. . Aducanumab binds to a different type of amyloid protein in the brain than BAN2401.
Biogen announced the updated results of a 24 – month trial on aducanumab Sunday at the conference. The latest data has shown a "beneficial effect" in cognition for patients with pre-Alzheimer's disease. He also showed a decrease in beta-amyloid plaque levels in a subgroup of ApoE ε4 gene transporters, the leading genetic risk factor for Alzheimer's disease. However, the full results of the study are not expected for a year or two.
The results of these two studies are intriguing, said the Alzheimer's Association.
"This is the second test to show amyloid reduction and some improvement in cognition," said Carrillo. "The amyloid hypothesis remains an important therapeutic target to pursue in the disease. # 39; Alzheimer's. "
The last drug against Alzheimer's disease approved by the Food and Drug Administration was in December 2014, and it was a combination of two existing drugs.Before, a new drug for the Alzheimer's disease has not entered the market since 2003. Of the five drugs approved by the FDA for treating Alzheimer's disease, none is slowing down its progression.
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