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RightEye’s Vision System for Early Diagnosis Named ‘Breakthrough Device’ by FDA

RightEye system

RightEye’s Vision System, an advanced eye-tracking device that measures eye tremors to help diagnose Parkinson’s disease at early stages, has been designated a breakthrough device by the U.S. Food and Drug Administration.

This FDA designation is given select medical devices or products that aim to more effectively treat or diagnose ” life-threatening or irreversibly debilitating diseases.” It streamlines processes to speed these devices’ development, testing, and agency review for approval, possibly allowing them to reach the market more quickly.

Currently, a Parkinson’s diagnosis relies on the outcomes of several neurological tests, and delays are common before a correct decision is reached.

“When assessing Parkinson’s disease, 60% of patients are misdiagnosed at least once, with one third of patients misdiagnosed twice. That is a terrifying and unacceptable statistic in the age of modern medicine,” George Gitchel, PhD, director of clinical research at the Southeast Parkinson’s Disease Research, Education, and Clinical Center (PADRECC), at the Richmond Veterans Affairs Medical Center, said in a press release.

“In my experience Parkinson’s patients often struggle for years, going from doctor to doctor trying to get a correct diagnosis,” Gitchel added.

Previous research has found tremors that prevent the eyes from fixing with stability are “pervasive” in people with Parkinson’s, and researchers have suggested that eye tremor be considered in diagnosing the disease.

The RightEye Vision System uses advanced eye-tracking technology to measure eye tremors, which usually develop in patients before other symptoms arise. This means that the device may help to detect Parkinson’s at early stages.

The size of a laptop, the system provides objective and accurate visual screening, generating reports that reflect hundreds of collected metrics.

“By providing quantitative, objective data to assist clinicians, I truly believe that RightEye will play a key role addressing this issue, while its FDA Breakthrough Designation will accelerate availability,” Gitchel said.  

The system received FDA clearance  for recording, viewing, and analyzing eye movements to help identify patients with troubled visual tracking in October 2018.

“With this FDA Breakthrough Device Designation, RightEye has an opportunity to address a critical unmet need in the fight against Parkinson’s disease,” said Adam Gross, co-founder and CEO at RightEye.

“The annual cost of Parkinson’s disease in America is estimated at approximately $52 billion. Earlier assessment, intervention, and more accurate diagnoses is anticipated to reduce these costs, while also improving patient outcomes and quality of life,” he added.

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New Large-Scale Data Portal Will Promote Parkinson’s Treatment Development

data portal

The Accelerating Medicines Partnership (AMP) for Parkinson’s (PD) has opened a data portal with de-identified information from 4,298 Parkinson’s patients and healthy control subjects for use by scientists seeking new treatments for the progressive neurodegenerative disease.

With unprecedented access to a data pool of this scale, investigators now can examine intricate data sets and conduct full-scale genomic analyses.

“AMP PD is a true example of the whole being greater than the sum of its parts,” said Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke (NINDS), in a press release. “The combination of many data sets could allow researchers greater power to analyze potential biomarkers for Parkinson’s disease. This effort follows other AMP programs which have the shared goal of changing the way we go about the business of studying disease.”

Launched in 2014, the AMP is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), multiple biopharmaceutical and life sciences companies, and non-profit organizations. Its goal is to transform the current model for developing new diagnostics and therapies by collaboratively identifying and validating promising biological treatment targets. The overarching mission is to develop new diagnostics and therapies relatively faster and at less cost.

Initial projects included Alzheimer’s disease, Type 2 diabetes, and rheumatoid arthritis, and lupus.

Last January, the AMP project on PD was launched. Managed by the Foundation of the National Institutes of Health (FNIH), the project includes the NIH, FDA, the Michael J. Fox Foundation (MJFF) for Parkinson’s Research, Celgene, Verily Life Sciences, Pfizer, Sanofi and GSK.

This project’s aim is to speed therapy development by providing the expertise and support necessary to learn which biomarkers demonstrate the most promise for predicting PD and disease progression. Biomarkers are molecular disease indicators.

“One important part of this platform is that, in addition to providing a place for storing complex data, we are also providing the tools to analyze that data within the platform itself,” said Debra Babcock, MD, PhD, NINDS program director and co-chair of the AMP PD steering committee. “In this way, we are bringing scientists to the data, which will increase opportunities for collaboration.”

Data in the officially named AMP PD Knowledge Portal was collected through the MJFF, NINDS and several other programs, studies and institutions. It includes information from samples of DNA, RNA, plasma, and cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. The portal also offers a platform that can assimilate additional types and sources of data. For example, there is an upcoming study involving proteomics, the large-scale study of proteins.

With the longitudinal data in the portal, scientists can study patients’ information throughout the disease course. And, the data have been harmonized, allowing for comparison of information from different programs, and providing best practices for how to incorporate into the platform data from the PD community.

“The AMP model has provided a unique platform for bringing together diverse patient cohorts, advances in technology and scientific expertise to study Parkinson’s disease on a scale that has not been attempted before,” said David Wholley, senior vice president, research partnerships, FNIH. “With the AMP PD Knowledge Portal, we are helping the scientific community worldwide to fast-track discoveries that we hope will ultimately help Parkinson’s disease patients and their families.”

Scientists may visit this site to apply for access to the knowledge portal and interact with the data set.

Globally, roughly 7 to 10 million individuals have Parkinson’s, the second most common neurodegenerative disorder after Alzheimer’s disease.

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Nourianz Now Available in US as Add-on to Carbidopa/Levodopa to Treat Parkinson’s Off Periods

Nourianz tablets

Kyowa Kirin’s Nourianz (istradefylline) tablets are now available in the United States as an add-on treatment for off periods in Parkinson’s disease patients on a carbidopa/levodopa regimen.

Off periods — when the effects of a medication wear off before a new dose can be taken — are characterized by the re-emergence of Parkinson’s motor symptoms and are typically more common as the disease progresses. Within five years of starting levodopa/carbidopa therapy, approximately 50% of patients may experience off periods.

“We are pleased to offer patients Nourianz, the first and only FDA-approved adenosine A2Areceptor antagonist treatment for ‘off’ time associated with [Parkinson’s],” Tom Stratford, president of Kyowa Kirin USA Holdings, said in a press release. “Nourianz administered with levodopa/carbidopa therapy can help reduce ‘off’ time and increase ‘on’ time without troublesome dyskinesia.”

Nourianz blocks a receptor, known as the adenosine A2A receptor, found at high levels in the basal ganglia, a region of the brain that controls movement. By blocking this receptor, Nourianz can alter the release of neurotransmitters — chemical substances produced in response to nerve signals that allow nerve cells to communicate — in the basal ganglia, regulating motor activity.

The U.S Food and Drug Administration (FDA) approved Nourianz in August based on the results of four randomized, placebo-controlled Phase 2 and 3 clinical trials (NCT00955526, NCT00455507, NCT01968031, and NCT00250393).

The trials assessed the safety and efficacy of two doses (20 mg and 40 mg) of Nourianz to reduce the mean total hours of awake time per day spent in the off state and also lessen motor symptoms.

A total of 1,143 Parkinson’s patients taking levodopa/carbidopa, levodopa/benserazide, or levodopa and any other dopa-decarboxylase inhibitor were recruited. Treatment with Nourianz significantly decreased daily off time, compared with patients on a placebo, and improved motor function.

The most common side effects of Nourianz included involuntary muscle movement (dyskinesia), dizziness, constipation, nausea, hallucinations, and insomnia.

“In my clinical practice, I see patients who experience the troublesome effects of Parkinson’s disease and ‘off’ episodes that interfere with activities of daily living,” said Peter A. LeWitt, MD, a professor of neurology at Wayne State University School of Medicine and director of the Parkinson’s Disease and Movement Disorders Program, Henry Ford Hospital.

“Nourianz represents an important milestone and provides U.S. patients and their caregivers with a nondopaminergic, once-a-day oral treatment option to significantly decrease the amount of ‘off’ time,” LeWitt added.

Nourianz has been marketed in Japan under the brand name Nouriast since May 2013.

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Nourianz Approved in US as Add-on Therapy to Carbidopa/Levodopa to Treat Off Periods in Parkinson’s

Nourianz FDA approval

The U.S Food and Drug Administration (FDA) has approved Kyowa Kirin’s Nourianz (istradefylline) tablets as an add-on therapy to treat off periods in Parkinson’s disease patients on a carbidopa/levodopa regimen.

Off periods — when the effects of a medication wear off before a new dose can be taken — are characterized by the re-emergence of Parkinson’s motor symptoms and are typically more common as the disease progresses.

Nourianz blocks a receptor, known as the adenosine A2A receptor, found at high levels in the basal ganglia, a region of the brain that controls movement. By blocking this receptor, Nourianz can alter the release of neurotransmitters — chemical substances produced in response to nerve signals that allow nerve cells to communicate — in the basal ganglia, in this way modulating motor activity.

FDA approval comes after the agency first rejected the therapy in 2008 due to concerns about its efficacy and asking for more data. Nourianz has been sold in Japan since 2013 under the brand name Nouriast.

“[This] approval is the culmination of decades of perseverance in exploring the science and clinical effects of istradefylline and inhibition of adenosine A2A receptor signaling in people with Parkinson’s disease,” Jeffrey S. Humphrey, MD, chief development officer of Kyowa Kirin Pharmaceutical Development, said in a press release. “We are grateful for the FDA approval and for the many dedicated scientists and  patients whose participation in our research programs has resulted in a new treatment option for Parkinson’s disease.”

The decision was based on data from four 12-week, placebo-controlled Phase 2 and 3 clinical trials (NCT00955526, NCT00455507, NCT01968031, and NCT00250393) that assessed the safety and efficiency of two doses (20 mg and 40 mg) of Nourianz to reduce the mean total hours of awake time per day spent in the off state and also lessen motor symptoms.

These trials enrolled a total 1,143 participants who were being treated with levodopa/carbidopa, levodopa/benserazide, or levodopa and any other dopa-decarboxylase inhibitor. Treatment with Nourianz significantly decreased daily off time when compared with patients on a placebo.

However, in 2016, data from one of the Phase 3 trials (NCT01968031), which evaluated the efficacy of Nourianz administered orally as a 20 mg or 40 mg once-daily treatment for 12 weeks, revealed a trend toward a greater reduction in the daily off-time compared with placebo, but this difference did not reach statistical significance.

New data from an interim analysis (which included 476 patients) of a post-marketing surveillance study conducted in Japan and submitted in October 2018 revealed that Nourianz was effective in 61.3% of patients, as assessed by the physician’s global assessment. Motor function improved, as observed by a decrease of 33.7 (after treatment) to 30.3 (from the beginning of the study) in the Unified PD Rating Scale (UPDRS) Part III (motor assessment) scores.

This new analysis also showed that off time was reduced in 38.2% of patients, and off-time symptoms improved in 44.7% of patients. Additionally, motor dysfunction was lessened in 48.5% of patients.

The most common side effects of Nourianz included involuntary muscle movement (dyskinesia), detected in 1% of the patients on Nourianz, dizziness, constipation, nausea, hallucinations, and insomnia. The FDA has requested that patients prescribed Nourianz are monitored for dyskinesia.

“Parkinson’s disease is a debilitating condition that profoundly impacts patients’ lives,” Eric Bastings, the acting director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research, said in an FDA press release. “We are committed to helping make additional treatments for Parkinson’s disease available to patients.”

Kyowa Kirin also has another adenosine A2A receptor antagonist, KW-6356, which is now undergoing testing in Phase 2 trials for Parkinson’s disease.

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Treatment with Stalevo and Comtan Does Not Raise Prostate Cancer Risk, FDA Finds

FDA review of cancer risk

A review by the U.S. Food and Drug Administration (FDA) found that Parkinson’s patients treated with medications containing entacapone are at no increased risk of prostate cancer.

As such, the agency stands by its current recommendations for the use of Stalevo (entacapone/carbidopa/levodopa) and Comtan (entacapone; brand name is Comtess elsewhere) to ease motor problems in Parkinson’s disease.

The FDA review was conducted after the findings of a Phase 3 trial, called STRIDE‐PD (NCT00099268), suggested that the entacapone component of Stalevo could raise a person’s risk of prostate cancer. The trial primarily aimed to test whether whether Stalevo or Sinemet (carbidopa/levodopa, by Merck) was more effective in lowering the likelihood of motor complications.

Notified of this concern, the FDA alerted the public in March 2010, the agency said in a release of its decision.

It also required Novartis — which markets both Stalevo and Comtan, and was the sponsor of STRIDE‐PD — to further investigate by comparing entacapone along with a conventional Parkinson’s regimen of dopamine decarboxylase inhibitor/levodopa (DDCI/LD) to treatment with DDCI/LD and either a dopamine agonist or a monoamine oxidase B (MAO-B) inhibitor. (DDCIs and MAO-B suppress the breakdown of levodopa and dopamine, respectively.)

Novartis’ study observed 11,396 male Parkinson’s patients in Finland, 1,141 of whom were using entacapone. Among all patients, 359 prostate cancer cases were reported over an average follow-up of 4.6 years, and 89 cancer-related deaths over 4.7 years. No significant difference in cancer development or death was seen between treatment groups.

Entacapone’s use in combination with DDCI/levodopa was also not linked to a greater risk of prostate cancer or mortality among patients using this combination for more than one year, the FDA found.

However, the agency noted limits to this observational study: Stalevo was available in Finland for a short time given the long latency of prostate cancer, men with advanced Parkinson’s are likely not examined regularly for this cancer, and little information existed as to patients’ family history of prostate cancer and prior screenings.

In parallel, the FDA conducted an independent study using data from the U.S. Department of Veterans Affairs health care system.

A total of 17,666 U.S. male veterans with Parkinson’s were included, all treated with Sinemet. Of these, 5,257 patients used entacapone as an add-on treatment, while the remaining 12,409 had as an add-on therapy a dopamine agonist or a MAO-B inhibitor (the study’s control group).

Twenty-three prostate cancer cases were reported among men on entacapone and 97 among those serving as controls over a follow-up period of 3.1 and 4.0 years, respectively. As with the study in Finland, treatment with entacapone did not lead to findings of a greater cancer risk, even analyzing patients using entacapone for more than two years.

The low overall incidence rate of of “1.8 cases of prostate cancer per 1,000 person-years compared to the age-adjusted rate of 1.3 per 1,000 U.S. males in the general population may reflect a possible bias in cancer ascertainment after Parkinson’s disease was diagnosed,” the FDA stated. (Person-years is a measure of both the number of people in the study and the amount of time each spends in the study. In other words, 1,000 person-years pertains to data gathered by following 1,000 people for one year.)

This rate could also partly be a consequence of lower rates of prostate cancer screening in the U.S., particularly among men with chronic conditions, it added, calling this a study limitation.

FDA officials advise healthcare professionals to follow standard prostate cancer screening recommendations. Patient and caregivers should stay on treatment as prescribed, and address questions or concerns with their doctors.

The FDA also urges both patients, caregivers, and healthcare professionals to report side effects to the agency’s MedWatch program using these options.

Comtess is marketed by Orion Pharma of Finland.

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FDA Accepts New Drug Application for Opicapone as Add-on Therapy

opicapone Neurocrine

The U.S. Food and Drug Administration has accepted Neurocrine Biosciences’ new drug application for opicapone as a potential add-on therapy to levodopa/carbidopa for Parkinson’s disease.

The FDA has set a 12-month review process, with a decision expected by April 26, 2020. If approved, the FDA will start its Prescription Drug User Fee Act (PDUFA), which authorizes the agency to collect fees from companies that produce certain human therapies and biological products. Since the passage of PDUFA, user fees have played an important role in expediting therapies’ approval process.

Opicapone, developed by Bial and Neurocrine Biosciences, is an oral, once-per-day add-on therapy to levodopa for adults with Parkinson’s, and end-of-dose motor fluctuations.

Levodopa is considered the gold-standard treatment for Parkinson’s. However, its long-term use is linked with end-of-dose, or wearing-off fluctuations, leading to progressively shorter intervals in which symptoms are adequately controlled.

Opicapone works by blocking the enzyme catechol-o-methyltransferase, or COMT, which breaks down levodopa. This can prolong levodopa effects, known as “on-time” or “on-periods.”

The therapy was approved in Europe for Parkinson’s patients with fluctuations that cannot be treated with lepodova or combinations of similar therapies, and whose motor symptoms re-emerge before the next dose is due. It is marketed by Bial in Europe under the brand name Ongentys. Neurocrine holds the rights for opicapone in North America.

Data from over 30 clinical trials, including two Phase 3 trials, BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655), support opicapone’s clinical benefits. The trials enrolled more than 900 Parkinson’s patients who could not effectively control their motor symptoms with standard therapies.

In the BIPARK-1 study, participants were randomly selected to receive 5, 25, or 50 mg daily doses of opicapone, plus either levodopa or Comtan (entacapone, marketed by Novartis), or a placebo. In BIPARK-2, opicapone was given as an add-on to either levodopa or placebo. Treatment was maintained for 14 to 15 weeks, after which participants had the opportunity to continue opicapone add-on therapy for more than one year in an open-label extension study.

Data from the BIPARK-1 trial showed that people treated with 50 mg opicapone had twice longer on-time periods without dyskinesia, or involuntary movements, compared with those receiving placebo (controls).

The BIPARK-2 study showed similar results. Participants taking 50 mg of opicapone had 1.7 hours of absolute on-time without dyskinesia compared with 0.9 hours in the placebo group.

The on-time periods were maintained in long-term extension studies for all opicapone-treated patients, with increases of 2 hours in the BIPARK-1 study, and 1.8 hours in the BIPARK-2 trial.

“People living with Parkinson’s disease often struggle to control their motor fluctuations due to the progressive neurodegenerative effects of the disorder. With opicapone, we aim to prolong the benefits of levodopa by providing a new treatment option to patients with Parkinson’s disease in the U.S.,” Eiry W. Roberts, MD, Neurocrine’s chief medical officer, said in a press release.

“It is our goal to help patients maintain good ON time — the period when their motor symptoms are better controlled — and reduce OFF time — the period when the effects of levodopa have worn off. We look forward to working with the FDA to bring this new treatment option to patients coping with this debilitating disorder,” Roberts added.

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Prevail’s Gene Therapy Candidate PR001 Granted FDA Fast Track Status

PR001 Fast Track

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to Prevail Therapeutics’ lead gene therapy candidate, PR001, for the treatment of people with Parkinson’s disease associated with GBA1 gene mutations.

Fast Track status will support and expedite the clinical development, regulatory review, and potential marketing approval of PR001.

The FDA’s decision follows its acceptance of Prevail’s Investigational New Drug application in June. That IND acceptance will allow the company to initiate a Phase 1/2 clinical trial to assess PR001’s safety and tolerability.

Prevail expects to launch the trial, and start dosing patients, during the second half of 2019.

“We are pleased that the FDA has granted Fast Track Designation for PR001, which underscores the unmet need of patients with Parkinson’s disease with a GBA1 mutation,” Asa Abeliovich, MD, PhD, founder and CEO of Prevail, said in a press release.

People who carry a mutated GBA1 gene can have up to 5 times higher risk of developing Parkinson’s disease. Even though it remains unclear what links the two conditions, it is estimated that 7 to 10% of all Parkinson’s cases are related to GBA1 mutations.

The GBA1 gene holds the instructions to produce the enzyme beta-glucocerebrosidase (GCase). That enzyme is essential for the digestion and recycling of different types of molecules and cellular debris in tiny vesicles called lysosomes. If GCase activity is impaired in any way, toxic substances accumulate inside cells, particularly as people age, leading to excessive inflammation and —probably, scientists say — the neurodegeneration seen in Parkinson’s disease.

PR001 is intended to be a disease-modifying and single-dose gene therapy for individuals with mutations in the GBA1 gene. It uses a modified and harmless version of an adeno-associated virus (AAV9) to deliver a fully working copy of the defective gene to nerve cells. This should allow for long-lasting expression of working beta-glucocerebrosidase, easing disease symptoms caused by the mutated gene.

Studies in mice and primates with Parkinson’s disease demonstrated that PR001 was well-tolerated. The gene therapy was found to promote an increase in GCase enzyme activity in mice. That resulted in reduced accumulation of fatty molecules, and improvements in motor function.

“With no treatments available that modify the progressive course or the underlying disease process of Parkinson’s disease, a potential disease-modifying therapy like PR001 could significantly transform the lives of patients with this disease,” Abeliovich said.

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FDA Grants Breakthrough Device Designation to Amprion’s PMCA Early Detection Tool

FDA breakthrough device

The U.S Food and Drug Administration (FDA) has granted a Breakthrough Device designation to Amprion’s proprietary technology, Protein Misfolding Cyclic Amplification (PMCA) — a device that holds the potential to diagnose Parkinson’s disease at a much earlier stage than current diagnostic methods.

If approved by the FDA, Amprion anticipates a market roll-out for PMCA tests as an early detection tool for Parkinson’s within the next 18 months.

There is no effective treatment for Parkinson’s, a progressive nervous system disorder that affects movement, largely due to the fact that there is no sensitive and objective laboratory test that can diagnose the disease at its early stages. Most patients are diagnosed due to clinical symptoms when the disease course is relatively advanced.

Amprion’s PMCA is able to circumvent this problem by tracking specific prion (proteins) biomarkers — in this case alpha-synuclein — in the cerebrospinal fluid (CSF) and blood prior to the onset of clinical symptoms. The CSF is the liquid surrounding the spine and brain.

“Our PMCA test tracks alpha-Synuclein, a protein that misfolds into toxic shapes in the brain and this likely begins decades before disease symptoms. Amprion’s ability to monitor Misfolded Proteins at early stages is both significant and meaningful. This enables us to work with major pharmaceutical companies to develop Prion-targeted drugs to stop or slow the disease,” Claudio Soto, PhD, Amprion’s co-founder and chief scientific officer, and a professor of neurology at McGovern Medical School at UTHealth, said in a press release.

The FDA’s Breakthrough Devices program gives expedited review and assessment to medical devices that have the potential to be an effective treatment or diagnostic tool for life-threatening or irreversibly debilitating diseases. This allows these devices to reach the market faster.

“Prions are proteins gone rogue. This is a small victory in our war against Prions,” said Russ Lebovitz, MD, PhD, and Amprion CEO. “We are honored and look forward to working closely with FDA to fast-track the development and review of our aS [alpha-synuclein] PMCA tests toward final regulatory approval. Early diagnosis of Parkinson’s represents a giant leap for science to crack the code on this disease. Our goal is to stop Parkinson’s on its destructive path.”

In addition to its value as a diagnostic test, the device may significantly contribute to medical research by providing scientists with a tool to study how alpha-synuclein contributes to Parkinson’s development.

The Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health SBIR/STTR programs, and McGovern Medical School at the University of Texas Health Science Center at Houston were key partners in the development of PMCA.

“Efforts across Parkinson’s research seek to better define, measure and treat alpha-Synuclein pathology. This assay is a valuable tool in that work and we’re proud that The Michael J. Fox Foundation could partner toward its development with funding, samples and consult,” said Samantha Hutten, PhD, the foundation’s senior associate director of research partnerships.

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FDA Declines to Approve APL-130277 for Treating ‘Off’ Periods; More Information Requested

APL-130277.

The U.S. Food and Drug Administration (FDA) has told Sunovion Pharmaceuticals that it is unable to approve APL-130277 (apomorphine sublingual film) in its present form for the treatment of Parkinson’s disease “off”  periods.

Sunovion submitted new drug application for APL-130277 in April 2018. Now the FDA has now issued a “complete response letter” in which it requests additional information, but no new clinical trials.

Off periods in Parkinson’s are characterized by the reappearance or worsening of symptoms — such as tremors and dyskinesia (involuntary movements) — due to a gradual decline in levodopa’s effectiveness as a therapy. About half of all patients on levodopa experience off episodes, which, although frequent in the morning after awakening, may occur multiple times throughout the day. These episodes become more frequent and severe as the disease progresses.

Noting the frequency and scarce treatment options for off periods, Antony Loebel, MD, Sunovion’s executive vice president and chief medical officer, said in a press release that “Sunovion remains committed to working with the FDA to address its requests so that we can bring apomorphine sublingual film (APL-130277) to patients as expeditiously as possible.”

Currently, Parkinson’s patients in the U.S. have only apomorphine — brand name Apokyn (apomorphine hydrochloride, US WorldMeds), as an approved medicine for off periods. Apomorphine is able to enter the brain quickly and, similar to levodopa, stimulate dopamine receptors to provide short-term relief. However, Apokyn’s subcutaneous (under-the-skin) delivery may cause pain and injection-site reactions.

In turn, APL-130277 is a sublingual (under the tongue) formulation of apomorphine, intended to provide on-demand and fast-acting lessening of all types of off episodes, meaning those that are unpredictable, and those that occur at the end-of-dose or after awakening in the morning. It was designed  to be taken up to five times a day, no sooner than two hours from the prior dose.

APL-130277 contains a two-layer film, one with apomorphine and the other including an acid neutralizer to improve absorption and reduce oral irritation. Compared to Apokyn, APL-130277 is less likely to induce nausea due to a more gradual absorption, said Loebel, who is also the head of global clinical development for Japan-based Sumitomo Dainippon Pharma Group (which owns Sunovion) in an October 2018 interview with Parkinson’s News Today.

The FDA new drug application for APL-130277 was supported by a 12-week, double-blind Phase 3 trial (NCT02469090). The results showed that, within 30 minutes of dosing, the treatment enabled a clinically meaningful reduction in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part 3 score, a measure of Parkinson’s motor symptoms, in comparison to placebo.

The benefits were seen as early as 15 minutes post-dose and were maintained for 90 minutes, when the last analysis was conducted. Similar improvements were seen at weeks four, eight and 12. A higher percentage of patients achieving a full-on response — or control of motor symptoms — within 30 minutes with APL-130277 also was observed.

The therapy was well-tolerated, with most treatment-related side effects being mild to moderate and reversible.

Most patients took the treatment two or three times each day, though no minimum dose was required. “So that indicates they’re getting a benefit and … it’s not given on a prescribed schedule — they chose to use it two or three times a day,” David Blum MD, Sunovion’s global head of neurology clinical research, said.

The company is still recruiting for a 24-week, open-label extension study (NCT02542696) at multiple locations. A total of 226 participants are expected to use APL-130277 at 10-35 mg. Outcomes focus on the safety and tolerability of longer-term use, including patient response without Tigan (trimethobenzamide), an antiemetic (a medicine against vomiting and nausea) required as pretreatment to Apokyn.

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Benefits of Acadia’s Nuplazid Outweigh Risks for Parkinson’s Psychosis Patients, FDA Reports

Nearly half a year after news reports surfaced about deaths allegedly linked to Nuplazid (pimavanserin) — a therapy for Parkinson’s patients with disease-related psychosis — the U.S. Food and Drug Administration says it could not find any new or unexpected safety concerns with the controversial treatment.
The agency said in a Sept. 20 press release that “after a thorough review, the FDA’s conclusion remains unchanged that the drug’s benefits outweigh its risks for patients with hallucinations and delusions of Parkinson’s disease psychosis.”
San Diego-based Acadia Pharmaceuticals, which produces Nuplazid, welcomed the announcement.
“As the only drug currently approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, Nuplazid is filling an important and previously unmet need,” Doral Fredericks, Acadia’s vice president for U.S. medical affairs, said in a statement emailed to Parkinson’s News Today.
She added that “we remain confident in the efficacy and safety of Nuplazid that supported its approval by the FDA and the reaffirmation the agency has given for the positive benefit-risk profile of Nuplazid in its most recent review.”
In that review, the FDA said it considered the fact that patients with Parkinson’s psychosis are more likely to die in the first place due to their older age, advanced disease, and other medical conditions.
“Moreover, Nuplazid is primarily distributed through a patient support program and a specialty pharmacy network, which increases the likelihood that deaths will be reported to the manufacturer,” said the agency, referring to its FDA Adverse Event Reporting System (FAERS). “In FAERS reports that included a cause of death (many reports did not provide sufficient information to assess drug cause and effect), there was no evident pattern to suggest a drug effect.”
It added that “overall, the postmarketing data were consistent with the safety data obtained from the premarketing controlled clinical trials of Nuplazid for Parkinson’s disease psychosis.”
The recommended dosage is 34 mg, taken orally as two 17 mg tablets once daily, with or without food.
The FDA’s recognition of Nuplazid’s complex safety profile after the medication’s April 2016 approval, the agency said in an April 2018 statement, “led to the inclusion of a Boxed Warning and the addition of other important warnings and precautions in the product labeling, so that healthcare professionals could have the risk/benefit information needed to make prescribing decisions.”
Concern over Nuplazid first surfaced following a CNN report in April. An article on the network’s website cited an analysis by the nonprofit Institute for Safe Medication Practices, which found that FAERS showed a total of 700 deaths — including 500 among Parkinson’s patients in which Nuplazid was the only treatment likely involved — in the nine months following Nuplazid’s June 2016 appearance on the market.
Nuplazid is targeted at treating Parkinson’s psychosis, which affects about 40 percent of the 1 million Americans believed to have the disease. According to CNN, the therapy — Acadia’s only product — generated $125 million in 2017 sales for the company.
The New York-based Michael J. Fox Foundation for Parkinson’s Research posted a bulletin about the FDA’s review on its website but offered no independent

Source: Parkinson's News Today