Affiris Announces Phase 2 Study of Potential Parkinson’s Vaccine


Affiris is preparing for a Phase 2 clinical trial to test Affitope (PD01A), an experimental medicine that, if successful, could lead to a vaccine against  Parkinson’s disease.

Affitope triggers the production of antibodies — molecules that recognize specific targets — against alpha-synuclein, a protein found in the brain that may be involved in transmitting information between neurons. While its precise function remains unknown, in the context of Parkinson’s disease toxic forms of this protein contribute to the death of neurons by clumping together into spherical structures called Lewy bodies.

By encouraging one’s body to develop its own defenses against molecules that contribute to Parkinson’s, Affitope works like a vaccine against the disease. In this way, a limited number of doses of Affitope might be able to replace other medicines that must be taken on a continual basis.

In its series of Phase 1 trials (NCT01568099, NCT01885494, NCT02618941, NCT02758730, and NCT02216188), Affitope showed long-term safety, effectiveness and tolerability, and appeared to provide the longest benefit when given as an initial injection, followed by a booster, as is done now for tetanus.

In general, vaccines work by creating a cellular “memory” of defense against the target molecule. As with other memories, this one fades with time. The booster shot serves as a “reminder.”

“Patients with neurodegenerative diseases such as Parkinson’s disease face an all-too-predictable future and are in urgent need of therapies that alter the course of disease progression. Although there are many treatments available to manage the devastating symptoms, sadly none of these acts on the underlying cause of the disease. However, AFFiRiS’ unique immunological approach provides a disease-modifying therapy with an excellent competitive [profile] in the field of neurodegenerative treatments,” Rossella Medori, MD, chief medical officer at AFFiRiS, said in a press release.

Although vaccinating against Parkinson’s is not a widespread strategy, Affiris is not alone. In late 2018, United Neuroscience developed its own candidate molecule to induce an immune response against alpha-synuclein, and Prothena is currently conducting a Phase 2 trial of an injectable antibody against alpha-synuclein (NCT03100149).

Founded in 2003, Affiris has been dedicated to using the immune system to cure neurodegenerative diseases. They currently investigate therapies for Parkinson’s, Alzheimer’s, multiple system atrophy, dementia with Lewy bodies, and Huntington’s disease.

Affiris has not announced when or where its upcoming Phase 2 Affitope trial will take place.

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ALZ-101 Vaccine Fares Well in Preclinical Study of Alzheimer’s Fish


Alzinova‘s ALZ-101 vaccine — designed to target toxic forms of the amyloid beta protein that drive neurodegeneration in Alzheimer’s disease — was well-tolerated in non-human primates and displayed efficacy in a fish model of the disease.

A clinical study in patients with early Alzheimer’s disease now is expected to start later this year.

Results of the study, “Oligomer-specific Active Vaccine Approach for the Treatment of Alzheimer’s Disease,” will be presented today by Anders Sandberg, PhD, chief scientific officer at Alzinova, during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related disorders, running from March 26-31, Lisbon, Portugal.

Alzheimer’s disease develops as a consequence of deposits of toxic clumps of mutant forms of amyloid beta protein in the brain. There are different forms of amyloid beta, however, the toxic form that promotes nerve cell death and neurodegeneration is its oligomer form — when several single units (monomers) of the protein aggregate.

Recent preclinical studies suggests that within amyloid beta oligomers, only a small subset carries full neurotoxic potential. These findings challenge the concept that developing therapeutics specific for amyloid beta oligomers will provide an efficient approach.

Researchers at Alzinova used AβCC peptide technology to isolate large fractions of Aβ42 oligomers, whose accumulation in the brain was identified as a determinant event triggering Alzheimer’s disease progression. The team used Aβ42 oligomers as a template to produce a specific vaccine against it, called ALZ-101.

Preclinical studies using a mouse model of Alzheimer’s disease showed that treatment with ALZ-101 led to a 25% increase in the number of synapses — the junctions between two nerve cells that allow them to communicate — in the brain of treated animals compared to controls (untreated).

For this study, researchers tested ALZ-101’s characteristics — specificity, safety, tolerability and its capacity to induce an immune response against amyloid beta oligomers — in non-human primates. The vaccine’s effectiveness also was assessed in freshwater zebrafish, which has been recognized as a suitable model to study various stages of Alzheimer’s.

Zebrafish were challenged with toxic human brain extracts, and researchers assessed the vaccine’s ability to rescue zebrafish embryos’ startle response. This is a rapid, generalized extreme response to a sudden, surprise stimulus and has been used as a readout for motor function, sensory physiology and basic forms of learning.

The results showed the vaccine was well-tolerated in non-human primates, with no signs of toxicity or inflammation. Moreover, despite targeting only a small fraction of amyloid-beta oligomers, the vaccine improved the ability of zebrafish embryos to learn the startle response after being challenged with toxic human brain extracts.

Overall, these findings suggest that “ALZ-101 is well suited as a long-term treatment option for preclinical and prodromal Alzheimer’s disease to prevent or delay the onset of dementia,” researchers wrote.

“A double-blind, randomized, parallel-group multiple dose study on the safety, tolerability and immunogenicity of ALZ-101 in patients with early Alzheimer’s disease is set to start in 2019,” they added.

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UB-311 Vaccine Safe in Mild Alzheimer’s Patients, Phase 2a Trial Shows

UB-311  Phase 2 trial

United Neuroscience’s vaccine candidate UB-311 was safe and well-tolerated in patients with mild Alzheimer’s disease, according to results from a Phase 2a clinical trial.

Patients who participated in this trial are now eligible to enroll in a long-term follow-up study that will continue to assess the vaccine’s safety for 108 weeks.

Trial results, “Active Immunotherapy with UB-311 vaccine: Results from a Phase IIa, randomized, double-blind, placebo-controlled, 3-arm parallel-group, multicenter study” were recently presented during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Lisbon, Portugal.

UB-311, developed by United Neuroscience, a spin-off of United Biomedical, is a synthetic peptide vaccine that triggers an antibody response against beta-amyloid — whose accumulation in the brain is a hallmark of Alzheimer’s disease — clearing it away without causing potentially harmful inflammation.

Results from a Phase 1 trial (NCT00965588) showed that UB-311 was safe and well-tolerated, and able to trigger high levels of anti-beta-amyloid antibodies in patients with mild to moderate Alzheimer’s disease. The data suggested that the treatment led to a stabilization of patients’ cognitive abilities.

The Phase 2a trial (NCT02551809), conducted at multiple sites in Taiwan, enrolled 43 patients, ages 60 to 90 years, with mild Alzheimer’s dementia. Most participants (81.4%) were APOE-E4 carriers, a genetic factor associated with a higher risk of developing early Alzheimer’s disease.

Patients were randomized to receive intramuscular injections of UB-311 at different doses or a placebo (control). Among those who received the vaccine, one group received a total of seven doses of UB-311 (three priming doses followed by four boosters) and the other group a total of five doses of UB-311 (three priming doses followed by two boosters) and two doses of placebo.

An effective vaccine usually requires more than one administration in the form of a prime-boost. After an initial immunization, a booster injection re-exposes the body to the same antigen, against which the body will create an immune response.

The study’s primary objectives were the safety/tolerability of the vaccine and its ability to trigger an immune response compared with the placebo after 78 weeks. Secondary goals included assessing the vaccine’s effect on patients’ cognitive, neuropsychiatric, and other functioning, including learning and memory assessed by positron-emission tomography (PET) imaging.

Magnetic resonance imaging (MRI) scans were obtained at the beginning of the study, and every three months following vaccination to assess amyloid-related imaging abnormalities (ARIA), meningoencephalitis (inflammation of the meninges and brain), and to track brain volume.

In agreement with recent top-line results, among the 41 patients who completed the 78 weeks, there were no cases of meningoencephalitis or ARIA-edema. The most common adverse events were injection site-related reactions and asymptomatic ARIA-hemosiderin (ARIA-H), which is characterized by small deposits of iron that manifest as dark spots on MRI images.

“To date, UB-311 has been well-tolerated, as continuously assessed by clinical exam and MRI, with over 300 vaccine doses administered from both Phase I and Phase IIa studies,” the researchers wrote.

Patients from this Phase 2 study are eligible to join the Phase 2 extension study (NCT03531710) that will evaluate the long-term safety, tolerability, and potential efficacy of UB-311. Patients will receive three or five doses of UB-311 for 96 weeks, followed by a 12-week follow-up period.

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UNS’ Investigational Vaccine UB-312 Holds Potential to Prevent Parkinson’s, Other Neurological Diseases, Data Show

UB-312 vaccine UNS

An investigational vaccine being developed by United Neuroscience (UNS) presented several advantages over traditional vaccines to treat progressive disorders, such as Parkinson’s disease, according to preclinical data.

The vaccine, called UB-312, was more selective to prevent toxic aggregates of alpha-synuclein in mouse models of the disease.

These latest findings were discussed during the Parkinson’s UK Research Conference 2018 held in York, England. The presentation “Anti-alpha synuclein active immunotherapy in Parkinson’s disease,” was given by Hui Jing Yu, PhD, medical director of UNS.

“We are very pleased with the promising results of UB-312 in both in vitro and in vivo preclinical studies, which supports our efforts to develop a convenient and cost-effective treatment for Parkinson’s disease,” Jing Yu said in a press release.

“With this platform, and thanks to the wonderful opportunity to participate in the Parkinson’s UK Research Conference, we will continue driving forward our efforts to improve the lives of millions of people suffering from neurodegenerative disorders,” she added.

To date, no safe and effective vaccine targeting disease-related forms of alpha-synuclein has been developed.

UNS is using its proprietary technology platform, UBITh, to develop a new generation of vaccines that enable more people, including elderly patients with weakened immune systems, to respond more robustly, more specifically, and with fewer side effects.

Its vaccines are designed to train a patient’s own immune cells to produce specific antibodies, also known as endobodies, that will target natural proteins that have started to behave abnormally and resulting in chronic diseases.

Preclinical studies have shown that UB-312-induced antibodies preferentially bind to disease-related forms of alpha-synuclein, prevent their aggregation, and even promote their disaggregation. This inhibition occurred while preserving motor function, body weight, and survival in mouse models of alpha-synuclein-mediated disease.

The potential therapeutic activity of UB-312 also was successfully assessed in brain tissue samples collected post-mortem from patients with Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.

“Aggregated alpha-synuclein plays a prominent role in multiple disorders of cognition, movement and autonomic function. The ability of UB-312 antisera to target toxic alpha-synuclein species in several disorders will allow us to address multiple neurodegenerative conditions including Parkinson’s disease,” said Ajay Verma, MD, PhD, chief medical officer of UNS.

The company already has initiated an observational study to establish a biomarker to determine UB-312’s potential in a trial-ready group of Parkinson’s patients in the United Kingdom. It also is planning to launch a Phase 1 trial in The Netherlands to explore the clinical activity of UB-312 by 2019.

“Expansion of UNS’ proprietary ‘Endobody’ vaccine technology platform to other targets affirms our goal of becoming a global leader in neurodegenerative disorders and asserts our vision of democratizing brain health,” said Mei Mei Hu, UNS’ CEO.

UNS’ lead vaccine candidate UB-311, which was developed to target amyloid-beta protein aggregates, is currently in clinical development in an ongoing Phase 2 trial (NCT02551809) in patients with mild Alzheimer’s disease.

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