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One-year Results in 2 Given Gene Therapy at Low Dose Showing Promise, Axovant Reports

early trial results

Two Parkinson’s patients treated with AXO-Lenti-PD, an investigative gene therapy, in an ongoing clinical trial continue to show improvement 12 months later, Axovant, the therapy’s developer, said in a release.

These findings at one year after treatment are important because this timepoint allows for a better assessment of therapy durability, and a more assured differentiation between placebo effects and therapeutic response, the company added.

AXO-Lenti-PD has shown encouraging results in these two people given a first low dose in the SUNRISE-PD (NCT03720418) Phase 1/2 clinical trial, which is now enrolling up to 30 patients at sites in France and England.

The treatment works by delivering three genes involved in dopamine production directly to the brain via a surgical procedure.

Dopamine is a neurotransmitter — a molecule involved in transmitting information between neurons — that is critical to coordinating movement. Dopamine-producing (dopaminergic) neurons are lost in Parkinson’s, and the resulting drop in dopamine levels is the cause of many disease symptoms.

By ‘infecting’ brain cells with the genetic instructions to increase dopamine production, AXO-Lenti-PD aims to turn other cells into dopaminergic neurons.

Current dopamine replacement therapies require continual oral doses of dopamine, whose effectiveness fades over time. The period between when one dose’s effectiveness wanes and the taking of a next dose can result in “off periods,” wherein patients report a return of symptoms such as poor motor control, stiffness, fatigue and mood changes.

Helping the brain to again produce adequate levels of dopamine would, in theory, eliminate the need for periodic oral doses, which could significantly limit off periods.

Previous studies in primate models of Parkinson’s found AXO-Lenti-PD to be safe and effective, and SUNRISE-PD results at three months’ post-treatment found that a one-time delivery of the therapy significantly improved patient scores on the Unified Parkinson’s Disease Rating Scale (UPDRS), a standard assessment of motor and non-motor symptoms associated with Parkinson’s.

The trial consists of two parts. Part A is an open-label, dose-escalation phase in which patients receive one of potentially three escalating doses of the gene therapy. In part B, a new group of patients will be randomized to either the ideal part A dose or to a sham procedure as an untreated control group. SUNRISE-PD’s goal is to test the safety, tolerability, and effectiveness of the potential treatment.

Both patients here, the first two enrolled, received the lowest dose (4.2×106 transducing units) of AXO-Lenti-PD.

One-year results show positive changes of 24 points and 20 points (respectively for the two patients) on the UPDRS Part III “Off” score, representing a 37% improvement in off-period motor symptoms, Axovant reported. Improvement at six months was 29%, as measured on the same scale.

These patients also showed an average 13-point positive change from baseline (study start) — representing a 44% improvement — on the UPDRS Part II “Off” score, which assesses daily life activities. On the PDQ-39 score index, another quality-of-life measure in Parkinson’s disease, these two showed an average 15-point positive change, or a 30% improvement from baseline to 12 months.

Both patients tolerated AXO-Lenti-PD well, and neither reported any serious side effects. One maintained a diary of on/off periods, which is useful in evaluating changes that might be due to therapy across time.

People being enrolled in SUNRISE-PD have had Parkinson’s for at least five years, have motor fluctuations and dyskinesia (jerky, involuntary movements), and are between the ages of 48 and 70.  More information can be found here.

The company expects to soon release six-month results on the first two patients given a second and higher dose of AXO-Lenti-PD. This dose is three times higher than that given the first cohort.

If dose-escalation results allow, Axovant expects to begin the randomized and placebo-controlled part B of the SUNRISE-PD as a Phase 2 study by the close of 2020.

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Gocovri ER Capsules Ably Ease Motor Symptoms But Care Needed with Elderly, Research Shows

Gocovri and its use

Gocovri (amantadine) extended release capsules work to help lessen dyskinesia, or involuntary muscle movement, and off episodes in Parkinson’s, but special care needs to be given elderly patients with poorer kidney function, according to data presented by Adamas Pharmaceuticals, the treatment’s developer, at a science conference.

Renal insufficiency — or inadequate kidney function, often due to blood flow problems — can be common in people starting around age 70. Doctors should carefully monitor their kidney health and adjust Gocovri doses accordingly, the researchers said, to prevent amantadine from accumulating at unsafe levels in their system.

Gocovri is an extended release prescription medicine for dyskinesia, the sudden and uncontrolled movements that Parkinson’s  patients experience on levodopa therapy, with or without use of other medicines working to increase the effects of dopamine — a chemical messenger— in the brain.

Although the therapy’s exact mechanism of action is not known, Gocovri has been shown to increase dopamine release and block its re-uptake, raising overall dopamine levels and easing motor symptoms.

Data from Gocovri’s development program and post-marketing surveillance were highlighted in five scientific posters at the International Congress of Parkinson’s Disease and Movement Disorders, running in France through Sept. 26.

In the study “The Effect of Gocovri on Motor Aspects of Experiences of Daily Living: Analyses of MDS-UPDRS Part II Data from a Phase 3 Program,” researchers assessed the impact of Gocovri capsules, taken at bedtime, on motor aspects of daily life in Parkinson’s patients.

Combined data from two Phase 3 trials (NCT02136914 and NCT02274766) found that 12 weeks of Gocovri treatment significantly improved motor skills and life activities in 82 treated patients, addressing such issues as freezing, tremor, eating, and getting out of bed/car/deep chair, compared to 87 patients given a placebo. According to the researchers, the improvement noted “was both statistically significant and clinically meaningful.”

In the study “Analysis of the Shape of the Gocovri Steady-state PK Profile: Implications for an Extended Release Product,” researchers detailed Gocovri’s pharmacokinetic profile — essentially, how the body affects a medicine.

Bedtime dosing of Gocovri resulted in a delayed, slow rise in amantadine concentrations. The analysis showed concentrations to be high in the morning and sustained throughout the day, but with minimal nighttime exposure, contributing to a sustained reduction in both dyskinesia and off episodes. (Off time refers to the periods when dopaminergic medication stops working, and motor symptoms reoccur.)

Three posters assessed the Gocovri’s safety. These assessments were made during the Phase 3 trials and throughout the year after the medicine was approved and made available to patients.

These posters are: “Gocovri Dose Adjustment in Elderly Parkinson’s Patients at Risk for Renal Impairment: Implications from an Exposure Simulation Model,” “The Efficacy and Safety of Gocovri Based on Age: Special Population Analyses of a Phase 3 Study Program” and “Safety of Gocovri in Clinical Practice: One-Year Post-Launch Pharmacovigilance Data.

The most common side effects reported with Gocovri use are dizziness, hallucinations, and falls. While the treatment did ease dyskinesia and other motor complications in all age groups (under 65 to older than 75) studied, adverse events were more frequent in people age 75 and older.

Elderly patients are also more susceptible to renal impairment, the researchers noted in these posters, and may have evidence of chronic kidney disease (defined by researchers here as renal function of less 50 mL/min/m2). In these cases, doctors need to adjust Gocovri doses to avoid drug accumulation, resulting toxicity, and dose- and exposure-related side effects.

“No dose adjustment of Gocovri is recommended on the basis of age alone; however, because renal impairment is common in elderly patients, care should be taken in dose selection, and it may be useful to monitor renal function,” they wrote.

Gocovri extended release is available at two different doses, as 68.5 mg and 137 mg capsules.

Side effects seen in prescription use closely mirror those observed in the Phase 3 trials, the researcher noted, including reports of hallucinations.

“Adamas’ purpose is to significantly improve the lives of people affected by neurological diseases, and we remain committed to the presentation of Gocovri data to provide further information to support robust clinical discussions,” Rajiv Patni, MD, the company’s chief medical officer, said in a news release.

“Our goal is to ensure that neurologists understand how Gocovri may be an option for their Parkinson’s disease patients with dyskinesia on dopaminergic therapies by providing them with a treatment that may increase functional on time by decreasing both dyskinesia and off,” Patni added.

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Onstryv Now Available to Patients with Parkinson’s Disease in Canada

Canada Onstryv launch

Patients in Canada with diagnosed Parkinson’s disease can now receive Onstryv (safinamide) to help manage their symptoms and their “off” episodes.

This follows the approval of Onstryv by Health Canada in January 2019 as an add-on treatment to improve motor function in Parkinson’s patients who experience “off periods” while taking other therapies such as levodopa.

The oral therapy will be available under prescription in 50 mg and 100 mg tablets, and be marketed in Canada by Valeo Pharma — under a license agreement with Zambon. Valeo has launched a physician awareness and information campaign to facilitate and expedite patients’ access to Onstryv.

“The number of Canadians afflicted with Parkinson’s Disease is expected to grow by more than 50% over the next decade as the Canadian population ages,” Steve Saviuk, CEO of Valeo, said in a press release. “Onstryv is the first new oral treatment for Parkinson’s Disease to be approved in Canada in well over a decade.”

“Valeo is committed to building and supporting relationships with healthcare professionals, patients and other stakeholders to build awareness and ensure access to this new treatment for Parkinson’s Disease,” he added.

Known as Onstryv in Canada and Xadago in the rest of the world, the compound is an oral, once-a-day add-on therapy that works by selectively and reversibly inhibiting the MAO-B enzyme that can degrade several neural signaling molecules such as dopamine, which is deficient in Parkinson’s disease. The therapy was approved in the United States in March 2017 by the U.S. Food and Drug Administration.

Onstryv was developed by Newron Pharmaceuticals and has demonstrated effectiveness in helping to control the motor symptoms and complications of Parkinson’s disease for over two years in patients. Zambon acquired rights from Newron Pharmaceuticals to develop and commercialize Onstryv globally.

Clinical trial data has shown that Onstryv can significantly reduce motor fluctuations (on/off time) when used in combination with levodopa and/or Lodosyn (carbidopa) without increasing the risk of dyskinesia (involuntary movements).

“Now, with the Canadian launch, safinamide is available across the North American region,” Stefan Weber, Newron CEO, said in a press release.

“This marks another key milestone for Newron and its commercial partners in providing availability of safinamide in Canada for the treatment of patients suffering from Parkinson’s disease,” he added.

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Gocovri Leads to Steady ‘On’ States in Parkinson’s Patients, Phase 3 Pooled Data Suggest

medications

Gocovri (amantadine) can effectively reduce the number and duration of “off” periods and dyskinesia (uncontrolled movement) episodes in Parkinson’s patients under long-term levodopa treatment, leading to a good steady “on” state, pooled Phase 3 clinical data show.

These findings were reported in a study, “Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials,” that was published in the Journal of Parkinson’s Disease.

Levodopa is a precursor of dopamine and one of the gold-standard treatments to manage the motor symptoms of Parkinson’s disease. However, patients who take it over extended periods develop off-episodes, moments in which the therapy losses its effect and involuntary movements (dyskinesia) reappear.

Some adjustments and alternative treatments, such as Gocovri (marketed by Adamas Pharmaceuticals), can help control these off-episodes and dyskinesia. But it is not clear how these treatments act as a whole.

Therefore, the researchers reviewed the effects of Gocovri from data collected during two Phase 3 placebo-controlled trials, called EASE LID (NCT02136914) and EASE LID 3 (NCT02274766).

The analysis included data from 162 Parkinson’s patients who participated in these trials, of whom 77 received Gocovri and 85 received a placebo for 12 weeks. The patients had a mean age of 64.5 years, had been diagnosed with Parkinson’s disease for 9.9 years, and had been taking levodopa for about 7.6 years.

During the trials, patients kept diaries in which they were asked to detail their daily on- and off-periods, and events of dyskinesia. Patients divided their awake time into 30-minute intervals and reported the state they were in at each interval.

Three main states were considered: “on” without troublesome dyskinesia (good “on”), “on” with troublesome dyskinesia (troublesome dyskinesia), and off-periods. Troublesome dyskinesia referred to involuntary movements that impaired, at least partially, the performance of daily functions.

Most patients (67%) reported waking up in an off-state, which decreased to 13% of patients during the first two awake hours. Thereafter, the number of patients in each state remained constant throughout the day.

A lower number of patients (5%) woke up experiencing troublesome dyskinesia, which in contrast increased up to 24% within the two hours after being awake, then fluctuated between 20% and 44% through the rest of the waking day.

Patients were found to experience a mean of 3.0 episodes of troublesome dyskinesia and about 2.2 off-episodes during the day. The mean duration of each episode was approximately two hours for dyskinesia and 1.1 hours for an off-episode.

After taking Gocovri for 12 weeks, the proportion of patients reporting no episodes of “on” with troublesome dyskinesia was 57.1%, compared with 24.7% in the placebo group. The treatment also reduced the mean duration of the episodes and the mean number of transitions between states during the day, leading to a steadier good “on” state during the day.

In general, the treatment was found to be safe, with less than 10% of patients experiencing adverse events. The most common adverse events were dizziness, constipation, hallucinations, dry mouth, edema, swelling of the extremities, and urinary infections.

“Our results demonstrated a treatment effect of Gocovri for dyskinesia and OFF [states] throughout the waking day,” the researchers wrote.

“In the future, wearable sensors and other types of monitors may provide continuous monitoring through the day and allow more sensitive assessment of mild motor fluctuations and dyskinesia,” they said.

Of note, most of the researchers received compensation from or are employees of Adamas Pharmaceuticals.

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#AANAM – L-DOPA Nasal Delivery System May Offer New Way to Manage Parkinson’s OFF Episodes

POD device powder L-DOPA

Impel NeuroPharma has developed an inhaler to administrate a powder formulation of levodopa (L-DOPA) so people with Parkinson’s disease can more easily manage their symptoms.

Evidence of the potential of this new treatment strategy was presented at the 2019 American Academy of Neurology (AAN) annual meeting in Philadelphia, in a poster titled “Preclinical Development of a Novel Precision Olfactory Delivery (POD®) – L-dopa Drug- Device Combination Product for the Treatment of OFF Episodes in Parkinson’s Disease.”

Levodopa is the gold-standard strategy used to achieve motor symptom relief in Parkinson’s disease. It is associated with the greatest improvement in motor function in these patients when compared with other available therapies designed to work in similar ways, and overcome the low dopamine levels in the brain that cause Parkinson’s.

Dopaminergic medications, including levodopa, enable Parkinson’s motor symptom control. However, as disease progresses, patients typically need to gradually increase treatment dose for maximum benefit and even after that they may still experience reappearance or worsening of symptoms (OFF periods) due to diminishing effects of the therapy. Evidence indicates that patients need to achieve 400 ng/mL L-DOPA levels circulating in the blood for their motor symptoms to ease.

The complexity of neurological disorders, the difficult access to the brain, and the high risks and costs of drug development represent serious disadvantages for improving therapies. Nose-to-brain drug transport offers an attractive alternative strategy attempting to enhance drug penetration into the central nervous system.

The Precision Olfactory Delivery (POD) device is a nasal therapy delivery system that allows easy access to a large tissue surface well-suited for rapid and consistent absorption of therapeutic compounds. Researchers manufactured more than 50 powder L-DOPA formulations and 30 of those were evaluated in preclinical animal models.

Researchers showed that using the POD system, it was possible to achieve 400 ng/mL L-DOPA levels circulating in the blood (the amount found to be clinically necessary to effectively ease motor symptoms) in about 5 to 12 minutes in non-human primates. This represents three- to five-fold improvement in levodopa delivery in comparison to currently available formulations.

Regarding anatomy or response to therapies, no other animal species is as close to humans as primates, so they are often used to test the safety and viability of therapies. They also allow an easier and truer extrapolation of findings to the “human reality,” making scientists better equipped to identify therapies that may reverse OFF episodes in Parkinson’s patients.

These preliminary results demonstrate that “a powder formulation of L-DOPA delivered to the vascular-rich upper nasal cavity with the POD device” can provide a way for self- or caregiver- administrated therapy and “achieve consistent and rapidly effective treatment to abort OFF episodes,” researchers said. “This work has led to the selection and further evaluation of a novel formulation in a Phase 2a clinical study.”

The study (NCT03541356) is currently recruiting patients with Parkinson’s disease at four clinical sites in Australia. For more information, visit the registry page here.

Up to 36 Parkinson’s patients, age 40 and up, will be randomized to take levodopa or a placebo administrated by a POD device. Researchers will assess the ability of the new formulation to manage OFF periods of motor symptom control, as well as its safety and tolerability.

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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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Gocovri Reduces Transitions Between Dyskinesia and ‘Off’ Episodes, Trial Results Show

Gocovri, dyskinesia

Treatment with Gocovri (amantadine) reduced Parkinson’s dyskinesia — involuntary, jerky movements — and so-called “off” episodes, leading to longer periods of controlling motor symptoms, Phase 3 clinical trial results show.

Parkinson’s motor fluctuations (off episodes) occur when the benefits of treatments such as levodopa wear off and symptoms re-emerge. About half of patients taking levodopa experience off periods, which become more frequent and severe as the disease progresses.

In August 2017, Gocovri, a long-acting and extended-release oral capsule formulation,  became the first and only treatment approved by the U.S. Food and Drug Administration for the treatment of dyskinesia in Parkinson’s patients receiving levodopa, with or without other dopaminergic medications.

According to developer Adamas Pharmaceuticals, Gocovri — designed to be taken once daily at bedtime — also is the first FDA-approved therapy to improve dyskinesia while reducing off periods in Parkinson’s patients.

During the study, 162 patients — 77 taking Gocovri and 85 placebo — provided a complete Parkinson’s home diary (either on or off states) at both baseline and week 12.

“The Parkinson’s disease home diary data from the Gocovri Phase 3 pivotal studies clearly show that the entire waking day may be impacted by troublesome dyskinesia,” Rajiv Patni, MD, chief medical officer at Adamas, said in a press release. Dyskinesia may happen after the patient takes the first daily dose of levodopa in the morning, he added.

Reductions in dyskinesia and off episodes with Gocovri at week 12 resulted in markedly longer on periods (when patients can control muscle symptoms) without dyskinesia.

Compared to placebo, Gocovri led to a 3.2-hour increase in the first on episode without troublesome dyskinesia.

Patients taking Gocovri also experienced 4.2 fewer transitions between diary states per day compared to 2.0 fewer transitions with placebo. Approximately 17% of Gocovri-treated patients did not experience any transitions during the day, compared with only 1% of those who took placebo.

The results, “ADS-5102 Reduces ON Time with Troublesome Dyskinesia and OFF Time Throughout the Waking Day-Time Course Analysis,” were presented recently at the 2nd Pan American Parkinson’s Disease and Movement Disorders Congress (MDS-PAS) in Miami.

“Gocovri-treated patients experienced a decrease in the number of transitions between these diary states, resulting in longer periods of uninterrupted on time without troublesome dyskinesia,” Patni commented, while noting that the 17% of Gocovri-treated patients who were transition-free throughout the waking day is “particularly noteworthy”.

“This new analysis provides a useful definition of transitions that reinforces the previously reported data of Gocovri on dyskinesia and off (periods),” Patni said.

Of note, safety results were consistent with the overall population of the pivotal trials for Gocovri, Adamas noted. The most frequent side effects, occurring in more than 10% of patients, were hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic (or postural) hypotension.

Gocovri’s benefits are in line with those of the EASE LID 2 (NCT02202551) open-label study, which evaluated the safety, tolerability, and effectiveness of a two-year treatment with Gocovri in Parkinson’s patients with levodopa-induced dyskinesia. Results showed that Gocovri could lead to long-term improvements of motor complications.

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Source: Parkinson's News Today

Sunovion’s Oral Apomorphine Film Seen to Ease Parkinson’s Off Periods in Phase 3 Trial

apomorphine trial results

Sunovion Pharmaceuticals’ apomorphine sublingual under-the-tongue film (APL-130277) — now under review for approval —  significantly improved motor fluctuations, or off episodes, in Parkinson’s patients in Phase 3 clinical trial, results show.

The double-blind pivotal study, (NCT02469090), evaluated the efficacy and safety of APL-130277 as a fast-acting oral treatment for Parkinson’s patients with off periods, including those experiencing early morning off episodes. These episodes typically occur in the period between the waning of benefits of medications such as levodopa and the time a next dose can be taken, when motor symptoms re-emerge.

A total of 109 patients were given either APL-130277 (54) or placebo (55). Their mean age was 62, and they had been diagnosed with Parkinson’s for a mean of nine years.

Results were presented at the 2nd Pan American Parkinson’s Disease and Movement Disorders Congress (MDS-PAS) that recently ended in Miami.

Compared to those on placebo, patients given APL-130277 had a statistically significant difference of 7.6 points in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score, a measure of motor skills and function. This test was preformed in patients just prior to treatment and again 30 minutes after dosing at week 12.

A statistically significant difference from placebo was seen as early as 15 minutes post-dose and persisted up to 90 minutes, the last time point measured. Similar improvements were observed in the double-blind maintenance period measured at baseline and at weeks 4, 8 and 12.

APL-130277 also led to a higher percentage of treated patients with a full on response — or control of motor symptoms — within 30 minutes at week 12.

Apomorphine sublingual (under-the-tongue) film was generally well-tolerated, with most treatment-related side effects being mild to moderate, and reversible, after its use was discontinued. Nausea, sleepiness, and dizziness were the most frequent adverse effects reported in the maintenance phase.

“Off episodes are disruptive to a person’s daily routine, so a possible treatment that can help alleviate these periods is important for the Parkinson’s disease community and healthcare providers,” Fernando L. Pagan, MD, director of the Movement Disorders Program at Georgetown University Hospital, said in a press release.

Pagan added that the results show promise for APL-130277 “as a fast-acting medicine for on-demand treatment of all types of motor off episodes.”

Sunovion intends APL-130277 to be a treatment for all types of off episodes, those that are unpredictable as well as those that occur at the end-of-dose or in the morning hours after awakening. The formulation is designed to be taken up to five times a day.

About half of all Parkinson’s patients taking levodopa experience off periods, which become more frequent and severe with disease s progression. Apomorphine is the only approved medication for off episodes in the U.S., available as Apokyn (apomorphine hydrochloride, US WorldMeds). But Apokyn is an injection treatment.

Sunovion recently announced that the U.S. Food and Drug Administration has accepted for review its request to approve APL-130277 to treat off episodes in Parkinson’s. The FDA’s decision is expected by Jan. 29, 2019.

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Source: Parkinson's News Today

FDA Accepts New Drug Application for Acorda’s Parkinson’s Therapy Inbrija

FDA review for Inbrija

The U.S. Food and Drug Administration has accepted Acorda Therapeutics’ New Drug Application for Inbrija (CVT-301) as a potential treatment for Parkinson’s disease.

Accepting the application means the agency is ready to start its regulatory review of the therapy. It expects to make a decision by Oct. 5, 2018.

Inbrija is an inhaled powder formulation of levodopa for the times when the punch of Parkinson’s patients’ oral levodopa and carbidopa regimen wears off. Doctors refer to such times as off periods.

Although levodopa is the most effective oral Parkinson’s therapy, many patients experience movement difficulties during off periods, which become more common as the disease progresses.

“Off periods greatly disrupt the lives of people living with Parkinson’s, and there is a significant need for new treatments in this community,” Dr. Burkhard Blank, Acorda’s chief medical officers, said in a press release.

The New Drug Application included results of the 12-week Phase 3 SPAN-PD clinical trial (NCT02240030), which covered 351 patients. It showed that a high dose of Inbrija administered up to five times a day improved patients’ movement during off periods, compared with a placebo. The results were in line with those of a Phase 2b trial.

FDA officials initially refused to accept the application for Inbrija — not because of safety or effectiveness concerns, but because of questions about its manufacturing process. Acorda addressed the questions in its resubmitted application.

“People with Parkinson’s and physicians need more options to manage this disease,” said Dr. Todd Sherer, the CEO of The Michael J. Fox Foundation. “Inhaled delivery of levodopa could help the many people living with Parkinson’s facing the complication of off periods as their disease progresses.”

The foundation funded some of the work of the therapy’s original developer, Civitas. Acorda acquired Civitas later.

Acorda uses its ARCUS delivery system to get Inbrija powder into patients’ lungs. From there it travels to the brain.

Oral and nasal-passage-delivered medications are administered through the digestive tract, getting to the brain slower.

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Source: Parkinson's News Today