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FDA Approves Kynmobi Sublingual Film to Treat Off Episodes in Parkinson’s

Kynmobi and FDA approval

The U.S. Food and Drug Administration has approved Sunovion’s Kynmobi (apomorphine hydrochloride) as an on-demand sublingual treatment for off episodes, or times when medication wears off, in people with Parkinson’s disease.

The medication, formerly known as APL-130277, is an apomorphine film that is placed under-the-tongue (sublingual administration) when patients start experiencing a worsening of their symptoms. It can be taken up to five times a day, at doses ranging from 10 mg to 30 mg.

Sunovion expects it to become available to patients in the U.S. by September.

“Today’s approval of Kynmobi advances treatment options for people with Parkinson’s disease who experience OFF episodes and the associated disruption of everyday activities,” Antony Loebel, MD, president and CEO at Sunovion, said in a press release.

“We are pleased to offer the Parkinson’s disease community a novel treatment option that we believe offers a convenient way for patients to rapidly improve impaired movements and better control their motor symptoms when they need it,” Loebel added.

Levodopa is considered the gold standard for Parkinson’s treatment. But several years after starting the medication, most patients begin experiencing fluctuations in their motor symptoms caused by a faster wearing off of the treatment’s effects. These “off” episodes can happen at any time of the day, and most patients experience more than one episode each day.

Kynmobi’s active ingredient, apomorphine, can cross the blood-brain barrier, a semipermeable membrane that protects the brain from the external environment, and mimic the effects of dopamine in the brain. As such, it can counteract the loss of dopamine-producing neurons in the brain, a hallmark of Parkinson’s.

Apokyn, by US World Meds, is an approved apomorphine injection treatment for Parkinson’s patients experiencing off episodes. Its efficacy in easing motor symptoms is established, but it can pose significant challenges to patients, such as the need for an under-the-skin injection, an initial dose titration that should be supervised in a clinic, and common side effects such as nausea and injection site complications. These challenges are thought to have limited its use.

Kynmobi is expected to provide an easier mode of administration and to be eliminate more slowly from the body, helping to ease the feeling of nausea caused by abrupt reductions in apomorphine blood levels.

“Several years after a person is diagnosed with Parkinson’s disease they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” said Stewart Factor, professor of neurology at Emory University School of Medicine.

“The approval of Kynmobi affords health care providers with a needed option that can be added to their patients’ medication regimen to adequately address OFF episodes as their Parkinson’s disease progresses,” Factor added.

Kynmobi’s approval was based on data from a Phase 3 study (NCT02469090), in which the oral medication was compared to placebo as an on-demand treatment of motor symptoms during off periods.

The trial included 109 patients who had at least two hours of total off periods per day, including well-defined morning off episodes, despite being responsive to levodopa treatment. In an initial open-label phase, all enrolled were given increasing doses of Kynmobi (10−35 mg) until an optimal dose was identified.

Patients were then randomly assigned to either Kynmobi or placebo, taken to treat up to five off episodes throughout a day, for 12 weeks. All continued to receive their stable anti-parkinsonian medications.

The trial’s main goal was improvements in motor symptoms — defined as changes on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III — from before dosing to 30 minutes after dosing at week 12.

Results showed that patients using Kynmobi experienced an 11.1 point reduction in their MDS-UPDRS scores at week 12, while those on placebo showed reductions of 3.5 points. This 7.6-point difference between both groups was significant, and clinical improvements were seen as early as 15 minutes after dosing, and persisted for up to 90 minutes.

Kynmobi also helped more patients (31%) achieve full control of their motor symptoms — a full “on” response — within 30 minutes at week 12, compared with 14% of those given a placebo.

The treatment was generally well-tolerated, with most treatment-related side effects being mild to moderate, and reversible after its use was stopped. The most common were nausea, sleepiness, and dizziness. One person with known cardiac risk factors who was treated with Kynmobi died due to heart failure.

“We know from our research and discussions with the Parkinson’s community that OFF episodes can significantly disrupt a patient’s daily life,” said Todd Sherer, PhD, CEO, The Michael J. Fox Foundation for Parkinson’s Research. “The Foundation supported early clinical development of sublingual apomorphine, and this approval brings an important new treatment option for people with PD [Parkinson’s disease] who experience OFF [periods].”

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Sublingual Film Turns Parkinson’s Off Periods ‘Full On,’ Most Patients in Phase 3 Trial Report

Phase 3 trial analysis

A majority of Parkinson’s patients in a clinical trial reported achieving a fully “on” response within 30 minutes of taking Sunovion‘s under-the-tongue apomorphine film, called APL-130277, about three months after starting its use to counter “off” episodes in this disease, a post-hoc analysis of study results found.

At week 12, 79% of the 54 adults using APL-130277 in the Phase 3 trial (NCT02469090) recorded a “full on” response to the at-home treatment as the effectiveness of their stable levodopa (or similar dopamine treatment) waned, scientists reported. These responses were a secondary study goal.

Results were presented at the recent Pan American Parkinson’s Disease & Movement Disorders Congress (MDS-PAS), Sunovion said in an email that also provided the presentation. It was titled “Patient-Reported Motor Responses to Apomorphine Sublingual Film Based on Home Dosing and Response Diaries.”

Meant to provide on-demand and fast-acting relief from all types of off episodes, APL-130277 is a formulation of apomorphine in a thin film. The film is placed under the tongue (called a sublingual medication), where it is absorbed into the bloodstream. This makes it easy to self-administer at any time and any place.

Apomorphine stimulates the production of dopamine in the brain. Dopamine is a powerful messenger molecule called a neurotransmitter produced in dopaminergic neurons. Dopaminergic neurons die off in Parkinson’s disease, which leads to the loss of motor and cognitive skills characteristic of the disease.

Off episodes are periods of worsening Parkinson’s symptoms that usually occur when a medication like levodopa begins to lose effect, but before the next dose can be taken. These symptoms include tremors, rigidity, and slowness, as well as cognitive impairment and mood disorders.

The Phase 3 trial randomly assigned 109 patients, with 54 given APL-130277 for on-demand and at-home use, and 55 others a placebo. All enrolled had reported experiencing one off period each day, and were currently taking stable doses of levodopa and adjunctive medications.

The study was double-blinded, so neither the patients nor the researchers knew who received the medication and who was using a placebo.

Over the course of its 12 weeks, patients recorded the time they took APL-130277 during any off episode they chose to treat, and their resulting motor status (full on or off) 30 minutes later. This information was self-reported in diaries over the two days prior to each clinic visit, made at study weeks four, eight and 12.

Researchers measured the percentage of “full on response” reports. That response was defined as one providing benefits “with regard to mobility, stiffness, and slowness, whereby normal daily activities could be performed and were comparable to or better than normal response to [Parkinson’s] medications prior to study enrollment.”

At the study’s conclusion, 79% of patients using the investigative film reported being fully on at 30 minutes after taking APL-130277, compared to 31% of those on placebo.

Across all weeks of diary entries, 77% of patients using APL-130277 reported full-on responses, compared to 26% on a placebo. All took either the treatment or placebo a mean of 2.2 and 2.5 times each day.

Those with full-on response also said they achieved it at all times of the day, with 71% reporting it between 5 am and 9 am, and 86% overnight, between 10 pm and 5 am. This is important, as off episodes can occur at any time.

“Based on home dosing and response diaries, the self administration of APL may lead to a FULL “ON” response in most patients experiencing “OFF” episodes throughout the day,” the researchers concluded.

APL-130277 is currently under review by the U.S. Food and Drug Administration for possible approval as a sublingual treatment for off periods in Parkinson’s disease. A decision is expected on or before May 24.

Meanwhile, enrollment is continuing in an open-label extension Phase 3 study (NCT02542696) investigating the long-term safety and efficacy of APL-130277. Patients are still being recruited at sites in Los Angeles and in several European countries. More information can be found here.

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FDA Accepts Resubmitted New Drug Application for APL-130277 Apomorphine Film, Sunovion Announces

APL-130277 resubmitted NDA

The U.S. Food and Drug Administration has accepted Sunovion‘s resubmitted new drug application (NDA) for APL-130277, an oral apomorphine therapy for treating off episodes in Parkinson’s disease.

The FDA had asked for additional information regarding APL-130277, following the first NDA in mid-2018. A response to this resubmission is expected by May 21.

APL-130277 is an under-the-tongue (sublingual) apomorphine film that may be easier for patients to take. The therapy is intended to provide on-demand and fast-acting lessening of all types of off episodes: periods of worsening symptoms that typically occur between the loss of a medication’s effect and when the next dose can be taken. These symptoms include tremors, rigidity, and slowness, as well as cognitive impairment and mood disorders.

Some 40% to 60% of those with Parkinson’s experience off episodes, which grow worse and more unpredictable over time.

“The unpredictable nature of off episodes can be extremely challenging and disruptive to the daily lives of people living with Parkinson’s disease as well as their care partners,” Antony Loebel, MD, president and CEO of Sunovion, said in a press release.

“We look forward to working with the FDA over the remaining review period,” Loebel added.

The agency had requested additional information — but no new clinical trials — before deciding whether to approve APL-130277. The new submission included additional analysis of clinical data, and information about the intended packaging of APL-130277, according to Sunovion.

Apomorphine crosses the blood-brain barrier — a network of blood vessels that allows the entry of essential nutrients to the brain while blocking potentially harmful substances and also some therapies — to stimulate dopamine production in the brain. Parkinson’s is biologically characterized by the loss of dopamine-producing (dopaminergic) neurons.

Other apomorphine medications, such as Apokyn, must be assembled and injected, which can pose a challenge for people with Parkinson’s. A common side effect to these medications is nausea, for which patients also must take an antiemetic.

In contrast, APL-130277 easily absorbs through the skin under the tongue and clinical trial participants reportedly tolerated it well without severe nausea. David Blum, MD, Sunovion’s global head of neurobiology, attributes this tolerance to a slower drop in the concentration of APL-130277 in patients’ blood, as compared with Apokyn. In past reporting, Blum has suggested that the sharp drop in blood Apokyn concentration may contribute to feelings of nausea. APL-130277, conversely, is absorbed quickly, but leaves the system in a slower, steadier fashion.

The treatment was seen in a Phase 3 clinical trial (NCT02469090) to ease the motor fluctuations associated with off episodes. During the study, participants received increasing doses of the compound over a 12-week period. Roughly two-thirds of 109 patients completed the trial. APL-130277 treated up to 5 off episodes throughout a given day. Some mild-to-moderate side effects, but none severe, were reported. Those reported included transient nausea, drowsiness, and dizziness.

Sunovion continues to recruit patients for an open-label extension study (NCT02542696) investigating the long-term safety and efficacy of APL-130277. Recruitment is open in Los Angeles and several European locations. More information can be found here.

If approved by the FDA, APL-130277 would be the first new treatment for off episodes in more than a decade.

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Sunovion Re-Submits Approval Request for APL-130277 to FDA for Treating Parkinson’s Off Periods

APL-130277 fda resubmission

Sunovion Pharmaceuticals has re-submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA), once again seeking the approval of its below-the-tongue formulation of apomorphine — called APL-130277 — for Parkinson’s off periods.

The re-submission is a follow-up to the FDA’s “complete response letter” from earlier this year, in which the agency requested additional information — but no new clinical trials — before deciding whether to approve APL-130277.

The new submission includes additional analysis of clinical data, and information about the intended packaging of APL-130277, according to Sunovion.

Off periods in Parkinson’s are characterized by the reappearance or worsening of symptoms such as tremors and dyskinesia, or involuntary movements. These effects are due to a gradual decline in the effectiveness of levodopa, which is the first-line therapy for the neurodegenerative disease. 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.

In the U.S., people with Parkinson’s currently have only Apokyn (apomorphine hydrochloride), developed by US WorldMeds, as an approved medicine for off periods. A form of apomorphine, the medicine is able to quickly penetrate the brain, where it stimulates dopamine receptors to provide short-term relief. However, Apokyn’s subcutaneous, or under-the-skin delivery may cause pain and injection-site reactions.

APL-130277 is a sublingual or under-the-tongue formulation of apomorphine, which may be easier for patients to take. It is intended to provide on-demand and fast-acting lessening of all types of off episodes — meaning those that are unpredictable, those that occur at the end-of-dose, or those occurring after awakening in the morning.

The therapy was designed to be administered up to five times a day, with a minimum of two hours from the prior dose.

This new formulation of the medication contains a two-layer film — one with apomorphine and the other with an acid neutralizer to improve absorption and reduce oral irritation. Compared with Apokyn, APL-130277 is less likely to induce nausea due to a more gradual absorption.

The new drug application for APL-130277, first filed in April 2018, was supported by a 12-week, double-blind Phase 3 trial (NCT02469090). The results showed that, within 30 minutes of dosing, APL-130277 induced 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 with placebo.

The benefits were seen as early as 15 minutes after dosing and were maintained for 90 minutes. Improvements were still detected at weeks four, eight and 12. A higher percentage of patients achieved a full-on response — or control of motor symptoms — within 30 minutes with APL-130277.

“OFF episodes in people with Parkinson’s disease can occur at any point throughout the day, often occurring in the morning after awakening and periodically throughout the day and can disrupt the ability to perform everyday activities,” Antony Loebel, MD, president and CEO at Sunovion, said in a press release.

“We look forward to continuing our dialogue with the FDA during the review period with the intention of bringing a much needed on-demand treatment option for OFF episodes to those living with Parkinson’s disease.”

An ongoing open-label extension study (NCT02542696) is testing the safety and tolerability of APL-130277 when used in the long-term. The trial is still recruiting at Los Angeles and at some European sites. More information can be found here.

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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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Sunovion Expects APL-130277 Will Ably Treat Off Episodes, Awaits FDA Decision

If the FDA approves Sunovion’s APL-130277 come January, Parkinson’s patients will have a first oral treatment — and a first new treatment in more than a decade — for off episodes, those times of difficulties with movement despite taking dopamine agonists like lepodova.
“We think that for the first time, we may have a product that can be used in a manner that is really effective, accessible, and helpful for patients who suffer from off episodes,” Antony Loebel, MD, Sunovion’s chief medical officer, told Parkinson’s News Today. The U.S. Food and Drug Administration accepted the company’s request to approve APL-130277 in June, and set Jan. 29 as a decision date.
Antony Loebel, Sunovion’s chief medical officer. (Photos courtesy of Sunovion)
Off episodes, or motor fluctuations, can come in a variety of forms. All affect a Parkinson’s disease patient’s ability to move voluntarily or cause unwanted movement (dyskinesia).
Some involve waking “up early in the morning and be frozen and not able to get out of bed until their morning dose kicks in, which can be in an hour. There are off episodes as the dose wears off,” said David Blum, MD, global head of neurology clinical research at Sunovion. “And there are more unpredictable off episodes that happen because of the internal bizarre nature of dopamine agonists like levodopa for Parkinson’s — erratic off episodes [and] delayed-on, where a patient takes a drug but it doesn’t act for a long time.”
About 40 to 50 percent of all patients experience off episodes, which generally become more severe and less predictable as the disease advances.
Parkinson’s is caused by the progressive loss of neurons that release a neurotransmitter, called dopamine, in the substantia nigra, a part of the brain that controls movement. Levodopa, an oral medication that is absorbed through a patient’s gastrointestinal tract and transported to the brain — where it is converted into dopamine — is considered the gold standard of Parkinson’s treatment.
Levodopa (combined with benserazide or carbidopa in a capsule or tablet) doesn’t stop or slow neuronal death. But it treats some of the disease’s most common symptoms, such as tremors and stiffness, by temporarily making more dopamine available.
Over time and with longer use, a patient’s response to levodopa diminishes and off periods become more frequent.
APL-130277 (apomorphine sublingual film) is not the only treatment targeting these episodes, but it may be more convenient and effective than Apokyn (apomorphine hydrochloride, US WorldMeds), approved in 2004.
Most off periods last 60 to 90 minutes, so any treatment needs to be fast-acting. Apomorphine — the active ingredient in both Apokyn and APL-130277 — can penetrate the brain quickly and stimulate dopamine receptors to provide short-term, levodopa-like relief. But it’s not easily absorbed when taken orally.
“If you deliver it in a way that bypasses oral absorption,” Blum said, “you can get a rapid rise in apomorphine levels … which kicks the patient from the off state to the on-state.”
David Blum, global head of clinical neurology at Sunovion.
Apokyn needs to be assembled and injected under the skin. Blum notes this can be a challenge for patients with movement disorders and their caregivers.
APL-130277 is a quick-acting sublingual treatment. Patients

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

Sunovion’s Request for Approval of Under-the-Tongue Apomorphine to Treat ‘Off’ Periods Under FDA Review

off periods and Parkinson's

The U.S. Food and Drug Administration (FDA) has accepted for review its request to approve apomorphine sublingual film (APL-130277) as a quick-acting, oral treatment of the motor fluctuations, or off episodes, associated with Parkinson’s disease.

Sunovion, which is developing the potential therapy, submitted a new drug application, or NDA, to the agency in April and the FDA’s decision is expected to by Jan. 29, 2019.

“We are encouraged that the FDA has accepted our NDA for apomorphine sublingual film,” Antony Loebel, executive vice president and chief medical officer at Sunovion, said in a press release.

“There are currently few treatment options available to Parkinson’s disease patients for the as-needed treatment of OFF episodes. We look forward to working with the FDA during the review period,”Loebel added.

Parkinson’s patients treated for long periods with levopoda, the most common first-line treatment for disease symptoms like tremors and stiffness, can develop motor fluctuations — “off-time” periods characterized by the return of these symptoms — as well as dyskinesia, or involuntary movements. These episodes occur as the result of the drug wearing off.

About half of all patients taking levodopa eventually experience off episodes, which become more frequent and severe as the disease worsens. Off periods can occur at any time — unpredictably or as a dose nears its end — although they frequently happen shortly after a patient awakens in the morning.

Despite its impact, therapies targeting off episodes in advanced patients are limited – the only approved medicine in the U.S. is apomorphine, marketed under the brand name Apokyn (apomorphine hydrochloride, US WorldMeds), administered as a subcutaneous injection. Its mode of administration can cause pain and injection-site reactions.

Sunovion’s apomorphine (APL-130277) was developed as an oral (under the tongue), on-demand and fast-acting therapy to lessen all types of motor off episodes. The company designed it to be taken up to five times a day.

It works by mimicking the action of dopamine, a neurotransmitter that facilitates communication between nerve cells. Parkinson’s motor impairments are caused by the death of dopamine-producing nerve cells in the brain.

Sunovion’s supported its FDA application with data from a 12-week Phase 3 study (NCT02469090) that tested the therapy’s effectiveness and safety in Parkinson’s patients whose levodopa had worn off.

Researchers measured its efficacy within 30 minutes after dosing, and looked at the percentage of patients who achieved a full response within that time window. The treatment met the study’s study goal, with initial results of 109 treated adults showing at 30 minutes a statistically significant mean reduction in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 3 score, a measure of Parkinson’s motor symptoms, compared to placebo at week 12.

Results also showed the therapy was well-tolerated, and continued to show persistent effects through 90 minutes after dosing, when a final measure was taken.

“Through our ongoing work with people living with Parkinson’s disease, we know the community is eager for more treatment options that may help alleviate OFF episodes, which are often disruptive to their daily lives,” said Todd Sherer, PhD, CEO of The Michael J. Fox Foundation for Parkinson’s Research. “We’re heartened to see apomorphine sublingual film is successfully continuing through the regulatory process, and we are hopeful for its approval and future availability.”

The clinical development of apomorphine was partly supported by the Fox Foundation.

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Source: Parkinson's News Today

Sunovion Seeks FDA Approval of Below-the-Tongue Apomorphine for Parkinson’s Off Periods

Off-periods therapy review

Sunovion Pharmaceuticals has asked the U.S. Food and Drug Administration to begin a regulatory review of its below-the-tongue formulation of apomorphine for Parkinson’s off periods.

The request is in the form of a New Drug Application for the formulation as a treatment for the periods when standard Parkinson’s drugs have worn off. Off periods are characterized by the return of both movement and non-movement symptoms. About half of patients taking the standard therapy levodopa have off episodes, which become more frequent and severe as the disease worsens.

Off periods can occur at any time, although they frequently happen right after a patient  awakens in the morning.

Sunovion refers to its therapy as apomorphine sublingual film (APL-130277). It is intended to kick in quickly, to reduce off periods. The company designed it to be taken up to five times a day.

Off periods, “which may be characterized by symptoms such as tremor, stiffness or slow movement, may disrupt the ability to perform everyday activities and may be burdensome for patients, families and caregivers,” Antony Loebel, the executive vice president and chief medical officer of Sunovion, said in a press release.

“We are pleased to have submitted the NDA [New Drug Application] for apomorphine sublingual film for the treatment of OFF episodes and look forward to working with the FDA during the review period,” said Loebel, who is also head of Global Clinical Development at Sunovion and its parent company, Sumitomo Dainippon Pharma.

Sunovion based the application largely on the results of a 12-week Phase 3 clinical trial (NCT02469090) that tested the therapy’s effectiveness and safety in Parkinson’s patients whose levodopa had worn off.

Researchers assessed the treatment’s effectiveness by looking at patients’ improvement in movement 30 minutes after dosing. The study also evaluated the percentage of patients who said they achieved a full response to the treatment within 30 minutes.

A key finding was that the therapy worked better than a placebo until 90 minutes after dosing. Patients also tolerated it well.

Sunovion will present the Phase 3 results at a future scientific conference.

The FDA had previously granted the treatment Fast Track Designation to accelerate its regulatory review.

The hallmark of Parkinson’s is loss of dopamine-producing nerve cells in the substantia nigra, an area of the brain that controls movement and coordination. Apomorphine has the same effect as dopamine, a neurotransmitter that facilitates communication between nerve cells.

Other formulations of apomorphine are the only approved treatments for Parkinson’s off episodes. It is available in the U.S. as an injection under the brand name Apokyn (US WorldMeds). However, this formulation can cause pain and injection-site reactions.

The post Sunovion Seeks FDA Approval of Below-the-Tongue Apomorphine for Parkinson’s Off Periods appeared first on Parkinson’s News Today.

Source: Parkinson's News Today