Alzheimer’s Vaccine Found Safe, Effective in Patients with Mild Forms of the Disease, Phase 2 Study Finds
AXON Neuroscience’s investigational AADvac1 vaccine against tau protein, a hallmark of Alzheimer’s disease, was found safe and effective at lessening signs of neurodegeneration in patients with mild Alzheimer’s, according to the results of a Phase 2 trial.
Among younger study participants, the vaccine also seemed to improve certain cognitive outcomes.
Intracellular tangles of tau protein are associated with neuronal loss and with severity of dementia. Immunotherapy using the AADvac1 vaccine is intended to induce the patient’s immune system to produce specific antibodies against abnormal forms of tau, with the ultimate goal of protecting neurons from degeneration.
The Phase 2 ADAMANT study (NCT02579252) randomized 196 patients with mild Alzheimer’s to receive ADDvac1 or a placebo. Patients were enrolled at 42 clinical centers in eight countries around Europe.
The vaccine was given in a total of 11 doses. The first six doses were administered at four-week intervals. The remaining doses were given at three-month intervals.
The trial’s main goal was to assess the vaccine’s safety. Additional goals included the vaccine’s immunogenicity (ability to produce an immune response) and effectiveness on clinical outcomes and disease biomarkers.
The results showed that AADvac1 was safe and well-tolerated, with no differences in adverse side effects between the ADDvac1-treated and placebo groups. The vaccine induced a robust immune response, with 98.2% of patients generating antibodies against toxic forms of the tau protein. These findings are in agreement with results seen in a previous Phase 1 study (NCT01850238).
Moreover, treatment with AADvac1 significantly lessened nerve cells’ death, as shown by the blood levels of neurofilament light chain (NfL). NfL is biomarker that can be measured in the blood or in the cerebrospinal fluid and reflects nerve cell damage in several neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis.
AADvac1 treatment halted the expected increase in NfL levels in the blood: while NfL increased by 27.7% two years post-treatment (compared to the start of the trial) in the placebo group, this change was only 12.6% in patients treated with AADvac1.
These results show that AADvac1 can slow the accelerated neurodegeneration observed in Alzheimer’s disease.
“Since AADvac1 targets pathological tau, I am truly impressed by the downstream effect on neurodegeneration indicated by the neurofilament findings. This effect, observed for the very first time in an Alzheimer’s trial, is a significant and much needed boost for the industry,” Philip Scheltens, MD, PhD, said in a press release. Scheltens is director of the Alzheimer Center at the Amsterdam University Medical Center, and the chairman of the scientific advisory board of Axon.
AADvac1-treated patients also showed a trend for reduced specific Alzheimer’s disease biomarkers, including the pathogenic variants of tau protein.
The vaccine also showed positive outcomes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb), a scale for assessing dementia severity, among the younger patient population. Additional cognitive goals that improved with AADvac1 included the Mini Mental State Examination and Activities of Daily Living questionnaire for Mild Cognitive Impairment, which measures patients’ abilities to perform daily living activities.
AADvac1 also lessen the levels of brain atrophy (shrinkage) and damage, which are associated with disease progression, as assessed by MRI and diffusion tensor imaging.
“Today’s results mark an important milestone for Axon, and for the entire population of the world that suffers from this devastating disease,” said Michal Fresser, CEO of Axon Neuroscience.
“Our vaccine is the first to solely target pathological tau proteins, which drive the cognitive decline and memory loss seen in Alzheimer’s. These results, which strongly reveal a disease-modifying effect on the disease, underpin our confidence to take the next steps in bringing a life-changing treatment to patients as soon as possible,” Fresser said.
Axon now plans continued testing AADvac1 in further clinical trials and is looking for a partner company to help plan and conduct the next trials.
Alzheimer's Vaccine Shown To Be Safe In Phase II Clinical Trial
Around 50 million people have dementia with 10 million new cases diagnosed every year. Alzheimer's makes up about 60 to 70 percent of all cases. Image Credit: pikselstock/Shutterstock.com
A potential vaccine against Alzheimer's has been found safe and capable of producing an immune response, new research has shown. The vaccine AADvac1 is a revolutionary approach in treating and preventing Alzheimer’s disease and has currently completed its phase II clinical trial, with some encouraging albeit limited results.
As reported in Nature Aging, the vaccine appears to be safe and stimulates an immune response against specific bits of the tau protein whose accumulation appears to be one of the causes of Alzheimer’s. While that is good news, the trial, in general, didn’t show a major impact on the cognitive decline of the patients, although a subset of them benefited from the vaccine.
Phase II randomized clinical trials are used to assess appropriate dosing levels as well as the efficacy of the drug. The team reports that the vaccine slowed down the accumulation of plasma neurofilament light-chain protein (NfL), which is a marker of neurodegeneration. However, more research will be necessary to assess if the vaccine stops and reverses the disease in a meaningful fraction of the population.
The trial had 196 participants from eight European countries, with 117 of them receiving the vaccine and the remaining 79 being given a placebo. They received 11 doses of the vaccine (or placebo) over the course of 24 months. Among them, the participants who had already been diagnosed with Alzheimer’s appeared to have the most beneficial effect from this trial, which is comforting to hear, although more investigation is needed.
“The recent approval of an amyloid-based therapy was encouraging for the whole Alzheimer’s industry. Unlike amyloid, which influences speed of Alzheimer’s progression, there is strong evidence that tau pathology relates to the underlying cause of the disease,” Norbert Zilka, the CSO of Axon Neuroscience, the company that developed the drug, said in a statement seen by IFLScience. “Our vaccine aims to halt the formation and spread of tau pathology, which has ultimately the potential to show a higher benefit for Alzheimer’s disease patients.”
Not all tau proteins are bad and the vaccine is designed to teach the immune system to recognize between good ones and harmful ones. The objective of AADvac1 is to slow down the formation of these damaging tau proteins and halt the spread of those already formed.
“The results confirm the disease-modifying effect of AADvac1, and support Axon’s progress toward a pivotal stage of clinical development. In view of the recent approval of amyloid-based therapy, our strong NfL endpoint results could serve as a surrogate in our forthcoming clinical development to achieve accelerated approval,” Michal Fresser, CEO of Axon Neuroscience, added.
According to the World Health Organization, around 50 million people have dementia with 10 million new cases diagnosed every year. Alzheimer's disease is the most common form of dementia with estimates placing it at about 60 to 70 percent of all cases.
Another Week Brings Another Tentative Alzheimer’s Advance
Research into Alzheimer’s disease took another tentative step forward as scientists said that an injection may help stall the damage wrought by the mind-robbing illness.
But much like last week, when U.S. regulators cleared the first new medicine in 18 years against the advice of agency advisers, the news was muddled. Only a subgroup of volunteers in the study of a therapy from Axon Neuroscience showed slowing of the most dreaded Alzheimer’s symptom: cognitive decline.
The researchers’ main goal was to determine whether the injection was safe -- and it was. Because it didn’t help cognitive or daily functioning in patients overall, the findings require caution and will need confirmation, the scientists said.
Axon, the closely-held biotech behind the research, targets tangles of a protein called tau in the brain, which the scientists view as related to the disease’s degenerative process.
The company’s Alzheimer’s vaccine was tested in almost 200 patients with mild disease over two years. However, lead researcher Petr Novak and colleagues believe that not all patients recruited for the trial had the disease, which can be hard to distinguish from other forms of dementia. Specifically, not all tested positive for the tau protein.
“Once we cut out these patients, then we see a significant difference on cognitive and neuro-degeneration markers,” Novak said in an interview.
Big Pharma Circling
In the subgroup of 109 patients whose brains contained tau tangles, volunteers who got the drug scored better than those given a placebo on a number of markers, including one that rates dementia by assessing variables such as problem solving, memory and orientation.
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Another school of Alzheimer’s research focuses on the buildup of a protein called amyloid, which clumps into plaques in patients’ brains. Amyloid plaques and tau tangles are hallmarks of the disease, but much of the scientific effort has focused on attacking amyloid. That abnormal protein is the target of the Biogen Inc. medicine that won U.S. regulators’ endorsement a week ago, becoming the first new Alzheimer’s therapy in almost two decades.
With its focus on tau, Axon has received a surge in interest from pharma companies lately, according to Chief Executive Officer Michal Fresser. The Slovakian company is now in talks with more than five potential partners for the Alzheimer’s therapy, its lead product, he said.
The U.S. decision to approve Biogen’s drug “opened some additional phone calls,” Fresser said. “After the Biogen results, the Alzheimer’s field has a lot more attractivity.”
The Axon vaccine, called AADvac1, is a type of injected immunotherapy treatment that induces antibodies against a toxic form of the tau protein typical of Alzheimer’s.
The trial results were published Monday in the medical journal Nature Aging -- almost a year after the study ended. Axon is now looking for a partner to help fund another trial with as many as 400 patients with confirmed Alzheimer’s that would start late this year or early next year.