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Trial Begins Testing Blood-derived GRF6019 Therapy for Severe Alzheimer’s Disease

GRF6019 severe AD

The first patient has been dosed in Alkahest‘s Phase 2 clinical trial testing its investigational therapy, GRF6019, in individuals with severe Alzheimer’s disease.

The study (NCT03765762) was designed to assess the safety and tolerability of the experimental treatment, as well as its impact on patients’ mental state and capacity to perform daily activities. Researchers will also collect information on overall symptom changes as reported by patients and their caregivers.

The trial is currently recruiting at sites in Arizona and Florida in the United States. Up to 20 participants with severe Alzheimer’s disease, as defined by Mini-Mental State Examination scores between 0 and 10, will be randomized to receive daily intravenous infusions of GRF6019 or a placebo for five consecutive days and followed for up to nine weeks.

Alkahest, and its collaborator Grifols, expect to announce results from this Phase 2 trial during the second half of 2020. For more information about the study, such as clinical site locations and contacts, click here.

“Patients at more advanced stages of Alzheimer’s disease are rarely included in clinical trials, and this novel approach could provide a novel treatment option for these individuals,” Karoly Nikolich, PhD, chairman and CEO of Alkahest, said in a press release.

GRF6019 is an investigational therapy that resulted from the separation of certain proteins from human blood plasma. Blood proteins that promote adverse immune reactions or treatment-patient incompatibilities — such as antibodies and clotting factors — are removed from GRF6019. Researchers believe this depletion process enhances the treatment’s safety and tolerability, and eases its administration. The therapy is also not restricted by blood type matching and is optimized for therapeutic uses.

Preclinical studies have shown that treatment with GRF6019 can improve learning and memory, reduce neuroinflammation, and support brain cells’ health in aged mice, which suggests that the product may hold therapeutic activity for several human neurological disorders, including Alzheimer’s disease.

In a previous open-label trial, called PLASMA (NCT02256306), researchers found that repeated intravenous infusions of plasma from young adult donors, 18 to 30 years old, into patients with mild to moderate Alzheimer’s could significantly improve functional activity in the patients.

“In recent years, it has become evident that there is a complex, multifactorial pathology underlying Alzheimer’s disease that available drugs and those currently in development fail to fully address,” Nikolich said. “Using our deep understanding of the plasma proteome, we have identified specific proteomic factors as the basis for this potential treatment for Alzheimer’s disease.”

Alkahest and Grifols are currently assessing the potential of GRF6019 in a second Phase 2 study (NCT03520998) in 40 patients with mild to moderate Alzheimer’s disease. Results from this study are expected to be announced by the end of 2019.

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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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Anavex 2-73 Trial Recruitment Reaches Halfway Mark

Anavex 2-73

A Phase 2 trial evaluating the efficacy and safety of investigational Anavex 2-73 as a treatment for Parkinson’s disease dementia has recruited half of its targeted patients, the therapy’s developer, Anavex Life Sciences, has announced.

The study is still recruiting Parkinson’s disease patients age 50 or older who have been diagnosed with dementia. The Phase 2 trial is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.

“We are encouraged by the rate of patient enrollment in this Phase 2 study and the potential for Anavex 2-73 to become a therapy for this unmet need given that up to 80% of Parkinson’s patients develop dementia,” Christopher U. Missling, PhD, president and chief executive officer of Anavex, said in a press release.

The Phase 2 trial (2017-004335-36expects to enroll 120 patients who will be randomized to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks. Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as patients’ motor function and sleep quality.

The study will also assess genomic precision medicine biomarkers, previously identified to respond to Anavex 2-73 in a Phase 2 trial (NCT02244541) in Alzheimer’s disease.

Anavex 2-73, originally developed as a potential disease-modifying therapy for Alzheimer’s, is given orally to activate a cellular receptor called Sigma-1 (SIGMAR1), known to have neuroprotective effects. Specifically, activation of SIGMAR1 can help reduce neuroinflammation, as well as the accumulation of beta-amyloid and tau proteins and oxidative stress, all known to contribute to the progression of neurodegenerative disorders.

According to a recent study published in the journal Cells, the therapy exerts its neuroprotective effects by re-establishing the normal functioning of cells’ “recycling system,” preventing the accumulation of toxic protein clumps.

Preclinical studies with mouse models of Parkinson’s disease have shown that Anavex 2-73 was able to restore the function of damaged nerve cells and significantly improve motor function.

Currently, only one medicine, Nuplazid (pimavanserin) is approved by the the U.S. Food and Drug Administration (FDA) as a therapy for hallucinations and delusions associated with Parkinson’s disease.

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First Patient Dosed with VY-AADC Gene Therapy in Parkinson’s Phase 2 Trial

RESTORE-1 Voyager VY-AADC

Voyager Therapeutics has begun patient dosing in a Phase 2 trial testing its investigational VY-AADC gene therapy in Parkinson’s patients whose motor symptoms are not responding adequately to oral medication.

The trial, called RESTORE-1 (NCT03562494), is recruiting participants across seven sites in the United States.

VY-AADC is a therapy that delivers the DDC gene, which provides instructions for making the AADC enzyme, directly to brain cells in the putamen region. The enzyme converts the standard-of-care Parkinson’s treatment levodopa into dopamine, the signaling molecule that is lacking in Parkinson’s disease.

The approach is expected to bypass the effects of degenerating dopamine neurons in the substantia nigra, a part of the midbrain, by increasing dopamine levels in the putamen.

In an ongoing Phase 1b trial (NCT01973543), a single administration of the therapy induced robust and durable improvements in patients’ motor function up to three years after treatment.

The treatment also effectively increased AADC enzyme activity, allowing patients to reduce their doses of oral levodopa. Also, patients reported significant improvement in quality of life.

The newly begun Phase 2 trial aims to determine whether VY-AADC is better than a placebo at reducing motor fluctuations in Parkinson’s patients whose symptoms are not effectively controlled with levodopa or related treatments.

The trial is expected to enroll approximately 42 patients who have been diagnosed with Parkinson’s disease for at least four years and are not responding adequately to oral medications. To be eligible, participants must be experiencing at least three hours of OFF time during the day, as measured by a validated, self-reported patient diary.

Participants will be randomized to receive either a single infusion of VY-AADC or a placebo into the brain via surgery. They will be followed for 12 months to determine their changes in motor fluctuations, changes in the ability to perform daily activities, and quality of life.

During the new Phase 2 trial, researchers will also determine the efficacy of treatment delivery by assessing AADC enzyme levels and activity in the putamen through positron emission tomography (PET). Changes in patients’ daily doses of oral levodopa and related medications will also be evaluated.

More information about RESTORE-1, including recruitment details, can be found here.

“Patients with Parkinson’s disease need new therapeutic options, especially as the disease progresses and there is less AADC enzyme in parts of the brain where it is needed to convert levodopa to dopamine,” Mark Richardson, MD, PhD, associate professor, director of Epilepsy and Movement Disorders Surgery at the University of Pittsburgh Medical Center and principal investigator in the RESTORE-1 trial, said in a press release.

The U.S. Food and Drug Administration granted regenerative medicine advanced therapy (RMAT) designation to VY-AADC for therapy-resistant motor fluctuations in Parkinson’s patients.

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Parkinson’s Gene Therapy Eases Motor Symptoms by Creating New Brain Circuits, Study Shows

AAV2-GAD gene therapy

An experimental gene therapy called AAV2-GAD, previously shown to improve motor function in Parkinson’s patients, works by creating new circuits in the brain involving motor regions, researchers have discovered.

Their findings were published in the study, “Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity,” in the journal Science Translational Medicine.

Neurodegeneration in Parkinson’s disease begins with the gradual loss of dopamine-producing nerve cells in the substantia nigra, a region of the brain responsible for movement control. However, at symptom onset, several changes in connectivity and metabolism (set of life-sustaining chemical reactions) in distinct areas of the brain are present.

The subthalamic nucleus (STN), which is key in the regulation of the motor circuitry, is one of the areas of the brain affected by Parkinson’s, becoming hyperactivated. Surgical interventions in this area, such as deep brain stimulation, have been pinpointed as a good therapeutic target to ease motor symptoms.

AAV2-GAD, developed by Neurologix, consists of a modified and harmless adeno-associated virus (AAV) that transports and delivers the glutamate decarboxylase (GAD) gene — which has the instructions to produce GAD, a key enzyme in the production of GABA, the major suppressive messenger molecule in the brain. AAV2-GAD is delivered through a surgical procedure.

Results from previous Phase 1 (NCT00195143) and Phase 2 (NCT00643890) clinical trials have shown that the administration of the AAV2-GAD gene therapy directly into the STN region resulted in significant motor improvements in Parkinson’s patients, which were maintained for at least a year.

Despite the promising results of AAV2-GAD, the precise mechanisms behind it remained unclear.

Scientists hypothesized, however, that the local delivery of the GAD gene to induce the production of GAD and GABA would convert STN nerve cells to a suppressive state and reduce their hyperactivity, ultimately easing Parkinson’s motor symptoms.

Clinical responses in Parkinson’s disease can, in theory, arise from changes in the underlying abnormal disease network, development of new networks, a placebo effect, or a combination of all three.

Previous studies have shown that Parkinson’s patients show a disease-specific metabolic network — known as Parkinson’s disease-related covariance pattern (PDRP) — and that this pattern can be used as an objective and sensitive indicator of disease progression and that its reduction is strongly associated with motor improvements, assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS).

Researchers at The Feinstein Institute for Medical Research, in Manhasset, New York, have now evaluated whether the motor improvements associated with delivery of AAV2-GAD to the STN were due to changes in PDRP or to other mechanisms.

They compared the brain metabolic networks of 36 Parkinson’s patients who participated in the previous double-blind, randomized, controlled Phase 2 trial: 15 in the AAV2-GAD group and 21 in the control group (sham surgery). These specialized brain scans were obtained at the beginning of the study, and six and 12 months after surgery.

“Current Parkinson’s disease therapies act on the abnormal disease network in the brain and often stop working over time as the body builds a tolerance,” David Eidelberg, MD, the study’s senior author and director of the Center for Neurosciences at the Feinstein Institute, said in a press release. “What we observed with AAV2-GAD therapy is quite the opposite.”

To the team’s surprise, AAV2-GAD did not change Parkinson’s abnormal brain circuitry, like current therapies, but instead promoted the formation of new brain networks connecting the STN to motor regions, which became mature one year after surgery.

Patients in the control group did not show this type of rewiring, and changes in UPDRS motor scores were found to be significantly associated only with the AAV2-GAD-specific brain metabolic network.

Data showed that while AAV2-GAD delivery to the STN did not act on the disease network, it induced the rewiring of key areas of the brain, compensating for the faulty circuitry and showing motor benefits for Parkinson’s patients.

The team noted that a larger Phase 3 trial is required to confirm these findings and the therapeutic effects of AAV2-GAD delivery to the STN, and that metabolic network analysis might be useful for evaluating therapeutic effectiveness in patients with neurological disorders in clinical trials.

“This latest work mapping the therapeutic benefit of AAV2-GAD gene therapy is a major next step to further refining therapies that combat the root causes of [Parkinson’s disease],” said Kevin J. Tracey, MD, Feinstein Institute’s president and CEO.

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Phase 2 Trial Testing Anavex 2-73 Recruiting Parkinson’s Patients With Dementia in Spain

Anavex 2-73 enrolling trial

The first patient has been enrolled in Anavex Life Sciences‘ Phase 2 clinical trial to evaluate the potential and safety of Anavex 2-73 as a treatment for Parkinson’s disease dementia.

Now actively recruiting, the study (2017-004335-36) is expected to enroll approximately 120 Parkinson’s patients ages 50 or older with a dementia diagnosis. It is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.

Anavex has been developing Anavex 2-73 as a potential disease-modifying therapy for Alzheimer’s disease. It is a small molecule that activates the sigma-1 receptor located in a cellular structure called the endoplasmic reticulum, which is critical for several cellular regulatory mechanisms.

“We are very pleased to initiate our first patient enrollment into the Parkinson’s disease dementia Phase 2 study of Anavex 2-73,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release. “This is an important step toward achieving clinical data for the second indication initiating this year for Anavex 2-73 also incorporating genomic precision medicine biomarkers.”

Trial participants will be randomly assigned to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks.

Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as on patients’ motor function and sleep quality.

During the study, researchers will also assess genomic precision medicine biomarkers associated with Anavex 2-73 that were identified in another Phase 2 trial (NCT02244541) in Alzheimer’s disease.

Additional information (in Spanish) on the trial can be found here. Patients and caregivers interested in taking part in the study can download and fill out a simple screening questionnaire that is available on the website to assist in discussions with their physician.

“Parkinson’s disease is an already prevalent disease among older individuals that is poised to become a much greater public health problem around the globe in the coming decades and is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes,” Jaime Kulisevsky, MD, PhD, principle investigator of the Phase 2 trial, as well as a professor at the Autonomous University of Barcelona and director of the Movement Disorders Unit of the Sant Pau Hospital in Barcelona.

Results from preclinical studies have shown that Anavex 2-73 has the potential to restore function to damaged nerve cells in mouse models of Parkinson’s disease. The compound was also found to target faulty proteins and poorly working mitochondria — the cells’ powerhouses — preventing oxidative stress and inflammation.

As of now, only one medication, Nuplazid (pimavanserin) is approved by the U.S. Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson’s disease.

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Xeomin Eases Tremor Severity, Improves Hand Function in People with Essential Tremor, Phase 2 Trial Shows

essential tremor, Xeomin

Intramuscular treatment with Xeomin (incobotulinumtoxinA) decreases tremor severity and improves hand function in patients with essential tremor of the upper limbs, according to Phase 2 trial results.

Results of the trial, titled “Efficacy and safety of incobotulinumtoxinA for upper-limb essential tremor in a randomised, double-blind, placebo-controlled trial using kinematics-guided clinical decision support,” was presented at the recent 2018 World Congress on Parkinson’s Disease and Related Disorders in Lyon, France.

Essential tremor — often misdiagnosed as Parkinson’s disease — is a progressive movement disorder, found in more people ages 40 and older. It mainly affects the hands and arms, but head, voice, and leg tremors may also occur.

Unlike Parkinson’s, which is associated with motor symptoms such as slow movement and muscle stiffness, essential tremor does not cause other health problems, although unsteady gait may be observed. Also, while patients with Parkinson’s typically experience tremors when their hands are at rest, those with essential tremor have them when using their hands.

Researchers conducted a randomized, double-blind Phase 2 clinical trial (NCT02207946) — sponsored by Merz Pharma, Xeomin’s developer — to evaluate the effectiveness and safety of a single, kinematics (motion)-guided intramuscular injection of Xeomin in adults with moderate to marked essential tremor in their upper limbs. The trial was conducted in the U.S. and Canada.

A total of 30 patients were included — 19 of whom were randomized to receive Xeomin, at a total dose of up to 195 Units, and 11 received a placebo. The participants all got an injection in the wrist, with optional injections into the shoulder and/or elbow. Muscle selection was based on each patient’s patterns of tremor, while doses per muscle were based on a kinematics-guided TremorTek analysis, which uses a combination of wearable movement sensors and computer software.

Differences between Xeomin and placebo were assessed at weeks four and eight for maximum wrist-tremor amplitude and motor performance, measured by the Fahn-Tolosa-Marin (FTM) Part B score. Analyses of tremor severity, with the FTM tremor scale, and grip strength were conducted over 24 weeks.

Treatment with Xeomin induced a trend toward decreased wrist-tremor amplitude, compared with placebo, at week four, and showed a significant improvement at week eight. Persistent anti-tremor effects were seen by motion measurements up to 24 weeks after a single injection of Xeomin.

The data further demonstrated that Xeomin significantly improved motor performance at both the fourth and eighth weeks. Maximum grip strength in the treated arm decreased by 20%, with no notable change in those on placebo. Although two patients receiving Xeomin reported localized finger-muscle weakness, none of the participants discontinued treatment due to muscle weakness.

“Kinematics-guided incobotulinumtoxinA (Xeomin) administration significantly decreased tremor severity and improved hand motor function versus placebo in patients with ET of the upper limb,” the researchers wrote.

Xeomin was recently approved by the U.S. Food and Drug Administration to treat adults with chronic sialorrhea, or excessive drooling, a common condition in Parkinson’s patients. It has also been approved for the treatment of adults with abnormal head position and neck pain due to involuntary contraction of neck muscles, abnormal spasm of the eyelids (blepharospasm) in patients previously treated with Botox (onabotulinumtoxinA), and to reduce muscle stiffness of the upper limbs.

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Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

Nilotinib Phase 2 trial

Nilotinib can modulate dopamine levels and metabolism, as well as prevent the formation of toxic alpha-synuclein aggregates, according to recent data from a Phase 2 clinical trial.

These findings suggest that Novartis’ investigational therapy has the potential to promote long-term benefits in patients with Parkinson’s disease.

The study, “Nilotinib increases dopamine metabolism and reduces oligomeric: total alpha-synuclein ratio in Parkinson’s disease,” was recently presented during the 2018 World Congress on Parkinson’s Disease and Related Disorders (IAPRD), Lyon, France.

Nilotinib is available under the brand name Tasigna as an approved treatment for certain types of leukemia. It blocks the activity of a protein called BCR-ABL that is known to support cancer development. But this protein also is intimately linked to several mechanisms in the brain, such as oxidative stress and alpha-synuclein-induced neurodegeneration, which play critical roles in Parkinson’s and other brain disorders.

Results of a small proof-of-concept Phase 1 trial (NCT02281474) performed at Georgetown University in Washington, D.C., revealed that treatment with two different doses of Nilotinib — 150 mg and 300 mg — could improve Parkinson’s patients’ motor skills and cognitive abilities. In addition, the treatment showed the potential to reduce levels of the protein alpha-synuclein, which is believed to contribute to destruction of brain nerve cells in Parkinson’s disease.

In the ongoing Phase 2 trial (NCT02954978) a total of 75 patients with mid-stage Parkinson’s disease with mild cognitive impairment were randomized to take one of four tested oral doses of Nilotinib -—150 mg, 200 mg, 300 mg, and 400 mg — or a placebo.

After a single treatment researchers evaluated several biomarkers of the disease, including the levels of alpha-synuclein and dopamine derivate compounds in patients’ cerebrospinal fluid (CSF).

The data revealed a significant increase in homovanillic acid (HVA) and DOPAC levels, suggestive of enhanced production and metabolism of dopamine just one to four hours after treatment.

Although researchers could not find significant changes in CSF total alpha-synuclein levels, low-dose Nilotinib therapy (150 mg and 200 mg) resulted in a reduction of the levels of abnormally clustered and toxic alpha-synuclein.

“The significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of Parkinson’s disease patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a long-term disease modifying effect,” researchers wrote.

“These results suggest Nilotinib, in a dose dependent manner, may have a symptomatic effect through modulation of brain dopamine levels. Additionally, the significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of PD patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a long-term disease modifying effect,” researchers wrote.

The team will continue the analysis of the collected data to further explore the impact of Nilotinib treatment on disease biomarkers’ levels both in the blood and CSF, after a single administration and 52-week daily treatment regimen.

A new Phase 2 trial, NILO-PD (NCT03205488), currently recruiting 135 participants, will further investigate the potential of Nilotinib in patients with moderate-to-advanced Parkinson’s symptoms.

The study will take place at 25 sites across the United States. It will compare the safety and effects on patients’ motor functions of once-daily Nilotinib versus placebo treatment, for up to 12 months.

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Source: Parkinson's News Today

Potential Treatment for Daytime Sleepiness in Parkinson’s Patients Moving to Phase 2 Trial

THN102 for daytime sleepiness

Theranexus announced it is starting a Phase 2 clinical trial investigating  THN102  as a potential therapy for Parkinson’s patients who struggle with inappropriate and excessive sleepiness during daytime hours.

The trial (2017-004475-31), which is planned to enroll 60 patients at 20 sites across Europe and in the U.S., was approved to start in Hungary, the French company announced in a press release. Requests to allow this trial have been submitted to regulatory agencies elsewhere.

Affecting almost half of all Parkinson’s patients, excessive daytime sleepiness is a common non-motor symptom of this disease.

The safety and tolerability of THN102 (modafinil/flecainide combination) capsules, given at two doses of each active agent — either 200 mg/18 mg or 200 mg/2 mg of modafinil/flecainide — will be compared to placebo.

Additional or secondary study goals include measuring the treatment’s effectiveness in easing sleepiness, improving patients’ attention spans, vigilance, and cognition, again relative to those given placebo.

Patients enrolled have disease-related excessive daytime sleepiness, denoted by a score of 14 or higher in the Epworth Sleepiness Scale, a self-administered questionnaire for which the highest score is 24. Eligible patients also are those who “complain of daytime sleepiness impacting their quality of life and/or daytime functioning (e.g., falling asleep while reading or watching TV, while eating or talking with other people),” according to the trial’s official page.

THN102 is a combination therapy of modafinil, a first-line treatment for narcolepsy (a sleep disorder characterized by excessive sleepiness) and flecainide, a compound that acts on glial cells of the central nervous system. The therapy showed a safe profile in healthy volunteers deprived of sleep in a Phase 1 trial (NCT03182413), and is being tested in people with narcolepsy in a Phase 2 trial (NCT02821715) in France.

No treatments are approved to help Parkinson’s patients manage excessive daytime sleepiness.

“We would like to thank the regulatory agencies with whom we are in contact and we are delighted with this first authorisation for the phase 2 study for our drug candidate THN102 in Parkinson’s disease,” Franck Mouthon, CEO of Theranexus, said in the release.

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Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73, Planned

Anavex 2-73

Anavex Life Sciences is planning to open a Phase 2 clinical trial testing Anavex 2-73, a potential oral treatment for patients with Parkinson’s disease dementia (PDD), this year.

Anavex 2-73 aims to treat PDD by binding to the sigma-1 receptor, located in a cellular structure called the endoplasmic reticulum and important to protein production and transport.

The proposed double-blind, placebo-controlled trial will evaluate Anavex 2-73’s ability to ease both cognitive and motor difficulties in Parkinson’s patients. A trial application is before European regulators, with plans to start this study in the second half of 2018.

According to the Parkinson’s Foundation, around 50 to 80 percent of Parkinson’s patients will develop disease-related dementia. Parkinson’s is characterized by the loss of neurons in a crucial brain area that controls movement, the substantia nigra. This loss, in turn, lowers brain levels of dopamine, a key player in nerve cell or neuronal communication.

With disease progression, these changes spread to other areas of a patient’s brain, affecting memory, attention, and thinking and reasoning.

“As many as 80 percent of people with Parkinson’s will experience Parkinson’s disease dementia and treatment options are limited,” Christopher Missling, president and CEO at Anavex, said in a press release.

Results of preclinical work, fully funded by the The Michael J. Fox Foundation for Parkinson’s Research, show that treatment with Anavex 2-73 was able to restore function to damaged nerve cells in mouse models of Parkinson’s disease. Data also demonstrated that it targets misfolded proteins and poorly working mitochondria — a cell’s energy source — to prevent oxidative stress, inflammation, and cellular stress.

“We are excited to progress our program to Phase 2, with a focus on the many patients with Parkinson’s disease dementia, and we remain focused on the discovery and development of potential treatments for neurological diseases with unmet needs, including Alzheimer’s disease and Rett syndrome,” Missling added.

Anavex filed an updated investigational new drug application to the U.S. Food and Drug Administration (FDA) earlier this year for a double-blind, Phase 2 study evaluating Anavex 2-73 in Rett syndrome. If approved, this trial is also expected to open in late 2018.

The company plans to open a Phase 2/3 trial of Anavex 2-73 in up to 300 people with mild-to-moderate forms of Alzheimer’s disease.  A Phase 2a dose-escalating study (NCT02244541) involving 32 people with probable Alzheimer’s was conducted at sites across Australia.

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Source: Parkinson's News Today