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h-Patch Device for Slow Apomorphine Infusion May Ease Off Periods in Advanced Parkinson’s, Valeritas Says

apomorphine treatment

Under-the-skin infusions of low-dose apomorphine using a wearable device called h-Patch may help in avoiding off periods and improving motor function in Parkinson’s patients, Valeritas, the technology’s developer, reports.

A preclinical study found that apomorphine delivered using h-Patch could be detected in the blood within two hours, with a gradual decline upon completing the 24-hour subcutaneous infusion. Valeritas is planning to present these results at an upcoming medical conference.

Apomorphine is a derivative of morphine with effects similar to dopamine, the neurotransmitter released by specialized neurons that are progressively lost in Parkinson patients. In patients with advanced disease, apomorphine is the only approved option for the acute treatment of off episodes, or periods when the medication wears off and before a new dose can be taken. Off periods are characterized by the resurgence of motor and non-motor symptoms.

It is available in the U.S. as an under-the-skin injection (Apokyn, by US WorldMeds), but has been associated with pain and injection-site reactions.

In prior clinical trials, single-dose, subcutaneous infusions of apomorphine have shown efficacy in suppressing off periods, reducing dyskinesia — involuntary, jerky movements — and improving motor scores of Parkinson’s patients. They also enabled significantly lesser use of levodopa, which has been associated with reduced effectiveness and with impulsive and compulsive behaviors when used for a number of years.

Infusion pumps in current use can be bulky, “requiring delivery of relatively large volumes of therapeutics [to] remain a barrier” to both patients and caregivers, Valeritas states a press release.

“This study highlights a new subcutaneous delivery of an old drug (apomorphine) which is commonly used in Parkinson’s,” said Santosh Kesari, chair and professor of Translational Neurosciences and Neurotherapeutics at the John Wayne Cancer Institute and Pacific Neuroscience Institute, both in California.

The h-Patch approach, Kesari added, “may offer a more consistent dose throughout the day” relative to oral dosing of apomorphine, and help improve functionality and quality of life. “Drug delivery for CNS disorders is still a significant barrier for optimizing new and old drugs,” he said.

Valeritas’ V-Go Wearable Insulin Delivery device for people with type 2 diabetes, which also uses the h-Patch technology, is marketed in the U.S. with the approval of the U.S. Food and Drug Administration.

“Valeritas continues to demonstrate the versatility of, and opportunities for its h-Patch technology beyond insulin delivery,” said John Timberlake, the company’s president and CEO.

“The h-Patch is a demonstrated patient-friendly, cost-effective, and powerful delivery method for a variety of therapeutics which we believe is ideal for subcutaneous delivery of apomorphine,” he added.

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CHMP Favors EU Approval of Inbrija to Treat Parkinson’s Off Periods

CHMP recommendation

The Committee for Medicinal Products for Human Use (CHMP) — an arm of the European Medicines Agency (EMA) — is recommending that Inbrija, by Acorda Therapeutics, be approved to treat off periods in Parkinson’s patients on a carbidopa/levodopa regimen.

The European Commission will review CHMP’s positive opinion, with a decision expected before year’s end.

“We are delighted that Inbrija has achieved this important milestone, and look forward to the EC’s final decision later this year. There are approximately 1.2 million people in the EU living with Parkinson’s. We estimate that 40% of these individuals experience off periods, which are considered extremely disruptive,” Ron Cohen, MD, president and CEO of Acorda, said in a press release.

Inbrija is a self-administered, inhaled formulation of levodopa developed to treat off episodes. These periods, when levopoda wears 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.

Inbrija delivers a precise dose of levodopa to patients’ brains that, because it is inhaled, bypasses the need to be absorbed in the digestive system. As such, it can deliver a higher and more consistent levodopa dose to the brain.

Inbrija is approved by the U.S. Food and Drug Administration (FDA) to treat Parkinson’s symptoms during off episodes. 

CHMP’s decision was based on clinical data from the Phase 3 SPAN-PD clinical trial (NCT02240030). The study evaluated the safety and effectiveness of two doses of Inbrija — 84 mg and 60 mg — or a placebo taken up to five times a day in 351 Parkinson’s patients experiencing off periods. Treatment was maintained for 12 weeks.

Results showed that Inbrija significantly improved patients’ motor function compared to placebo. Researchers found no safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Trial outcomes were published in The Lancet Neurology, in the study “Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial.”

Inbrija was also studied in two long-term Phase 3 trials — the CVT-301-005 trial (NCT02352363) and the CVT-301-004E study (NCT02242487) – that evaluated Inbrija used up to five times daily for 12 months.

Researchers found no changes in treated patients’ lung function compared with standard levodopa treatment, supporting Inbrija’s safety as an off-period medication.

Efficacy data from the CVT-301-005 trial also confirmed that Inbrija eases problems with motor function that emerge in off periods. Treatment was found to enable symptom control within 60 minutes of the dose and lowered the length of patients’ off times.

Acorda’s European application covers all European Union countries, as well as Norway, Liechtenstein, and Iceland.

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‘Framing OFF Through Art’ Exhibit on View at World Parkinson Congress

Artworks focus on off periods

More than 1 in every 3 — some 40 percent — of Parkinson’s patients have “off periods,” the return of motor and non-motor symptoms as the effectiveness of a  treatment’s dose wears off. Artworks created in collaboration with patients, part of an Acorda Therapeutics program, are helping to express what these periods are like and focus attention on them.

Called Framing OFF Through Art, the six-piece exhibition was recently featured at the 5th World Parkinson Congress in Kyoto, Japan, attended by more than 3,000 people from at least 60 countries. The initiative is the centerpiece of Acorda’s Live Well. Do Tell program, launched last year.

Off periods are characterized by the re-emergence of Parkinson’s symptoms, such as sadness and anxiety, when the effects of levodopa/carbidopa wear off. Such episodes are typically more common as the disease progresses, and vary from person to person.

Because off periods can be difficult to discuss or even identify, the artwork is intended to visualize feelings associated with them. The hope is that the art will spur other patients to recognize their “off” symptoms, and discuss them with their care team. The artists who created the pieces have been touched in some way by Parkinson’s.

”Research has consistently shown that off periods are among the most common issues for people living with Parkinson’s disease,” Ron Cohen, MD, Acorda president and chief executive officer, said in a news release.

“We believe that people with Parkinson’s will be able to see aspects of their own experiences with Parkinson’s and off periods in these works of art.”

The artwork ranges from acrylic sculptures to oil paintings. Each artist was paired with two patients and their caregivers. The exhibition debuted in October at a New York event where the artists, patients and caregivers were guests. The need to better understand off periods, as well as how to discuss them, is highlighted in the Live Well. Do Tell statement of need.

As part of a rotating series, a piece called “Rooted Resilience” is featured on the Live Well. Do Tell website. Created by abstract impressionist and colorist Tim Kinney, who has several friends with Parkinson’s, the multi-color painting of a tree depicts the way Gustavo Pavon, diagnosed in 2006, described his off periods.

The painting’s transition from dark roots to the brightness of the leaves and sky is meant to illustrate emergence from an off time.

Marcela Del Bosque, Pavon’s wife and caregiver, is mentioned in a narrative accompanying the painting as describing the transition in this way:

“When Marcela saw the painting, she immediately picked up on this and noted that when Gustavo is in a dark place — in an off period — he’s quiet and doesn’t smile. Then, Gustavo’s bright smile that she loves reappears and he returns.”

The work’s branches and colors also symbolize Pavon’s growth — his “branching out” —  to embrace community support and speak more openly about his experience. For nearly a decade, Pavon had only told a few people about his condition and off symptoms that include shivering and stiffness.

Go here to learn more about off periods and for additional resources.

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Onstryv Now Approved for Parkinson’s Patients in Canada

Onstryv approval Canada

Onstryv (safinamide) has been approved for the treatment of Parkinson’s disease in Canada, where roughly 100,000 individuals live with the disorder.

The announcement was made by Quebec-based Valeo Pharma and Italian pharmaceutical conglomerate Zambon, the commercialization partner of Newron Pharmaceuticals, a biopharmaceutical company focused on the development of therapies for diseases of the central and peripheral nervous system.

The agreement with Zambon calls for Valeo Pharma, a specialty pharmaceutical company dedicated to commercializing innovative prescription products, to be responsible for all regulatory requirements, quality, sales and marketing, and drug distribution. Onstryv is expected to be available in Canada by June.

”The approval of safinamide in Canada is a step forward for patients who need new treatment options for Parkinson’s disease,” Roberto Tascione, Zambon’s CEO, said in the press release. “Our mission is to make this medication available to as many [Parkinson’s disease] patients worldwide as possible.”

Known as Onstryv in Canada and Xadago in the rest of the world, this compound is an oral, once-a-day, add-on therapy developed by Newron, and approved in the United States in March 2017 by the U.S. Food and Drug Administration to improve motor function in Parkinson’s patients who experience “off periods” while on treatment with levodopa and/or Lodosyn (carbidopa).

While partially effective, therapy using either or both levodopa and carbidopa results in debilitating fluctuations between a state of normal motor function (known as “on episodes”) and reduced motor function (“off periods”) as the treatment’s effectiveness wears off. What’s more, the increased doses necessary as the disease progresses frequently cause uncontrolled involuntary movements, a condition known as dyskinesia.

Onstryv raises the level and function of dopamine in the brain, both through the reversible blockage of the enzyme monoamine oxidase B that normally breaks down this chemical, and by inhibiting transporters responsible for its absorption and retention. In addition, the medicine inhibits the excessive release of the signaling molecule glutamate.

Following four randomized, double-blind, placebo-controlled Phase 3 trials, published results indicated that the addition of Onstryv increased the frequency of on episodes, decreased off periods, and improved motor function in levodopa-treated patients.

In 2017, Valeo and Zambon announced a partnership granting Valeo exclusive Canadian rights to commercialize Onstryv. In addition to Canada and the U.S., the medicine is approved in the European Union and Switzerland and was recently approved in Australia.

“There is a growing need for new treatments to manage Parkinson’s disease, and Onstryv provides an important option for patients that require better control of their symptoms,” said Steve Saviuk, Valeo’s CEO. “We look  forward to launching the first new oral treatment for Parkinson’s disease in over a decade to Canadian patients in need of a new therapeutic choice.”

In recent related news, a review study found that, along with cannabinoids and opioids, Onstryv may relieve Parkinson’s patients’ pain, a frequent non-motor symptom.

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Inbrija Approved in US to Treat Off Periods in Parkinson’s Patients on Carbidopa/Levodopa

Inbrija

The U.S. Food and Drug Administration has approved Inbrija (levodopa inhalation powder)‎ for the treatment of Parkinson’s off periods in patients on a carbidopa/levodopa regimen.

Acorda Therapeutics’ therapy is expected to be available by prescription in the first quarter of 2019. It will be distributed through a network of specialty pharmacies in the U.S.

“Today’s approval of INBRIJA marks a major milestone for both Acorda and the Parkinson’s community, for whom we are gratified to have developed this much needed therapy,” Ron Cohen, MD, Acorda’s president and CEO, said in a press release. Cohen noted the more than “two decades of research and development” needed for this approval, as well as the “enormous perseverance and ingenuity” by Acorda’s team.

Inbrija is a self-administered, orally inhaled levodopa treatment for off periods, which are characterized by the re-emergence of Parkinson’s motor symptoms due to low levels of dopamine between doses of standard treatment. These off episodes are typically more common as the disease progresses.

The Michael J. Fox Foundation helped to fund the early development of Acorda’s medication, a decision based on the impact off periods have on patients’ lives, according to Todd Sherer, PhD, the foundation’s CEO.

“We knew we had to help address this unmet need, and this approval is a significant step forward for the community as it provides a new option to manage these gaps in symptom control,” he said.

Inbrija uses Acorda’s ARCUS technology, a system designed to deliver medication to the lungs through inhalation. ARCUS transforms molecules into a light, porous, dry powder, enabling the delivery of much higher doses of medication.

The FDA’s decision was based on a clinical program that included approximately 900 Parkinson’s patients. The pivotal Phase 3 SPAN-PD trial (NCT02240030) evaluated the efficacy and safety of 84 mg and 60 mg of Inbrija in 351 participants with mild to moderate Parkinson’s who were experiencing off periods.

Results of the double-blind study showed a statistically significant improvement in motor function at the final 12-week visit, seen by a reduction in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) score with Inbrija’s higher dose, compared with placebo, at 30 minutes post-dose. Inbrija’s effects were seen as early as 10 minutes after treatment.

The most common adverse reactions with Inbrija were cough, upper respiratory tract infection, nausea, and discolored sputum, which may indicate a bacterial infection.

Treatment with Inbrija was also analyzed in a one-year, randomized, open-label Phase 3 trial with 398 participants (NCT02352363). Results showed a similar average reduction in forced expiratory volume in one second — a measure of pulmonary function — in the Inbrija (84 mg) and observational groups.

Inbrija also eased Parkinson’s symptoms at all time points, as measured with the UPDRS-III scale, enabled symptom control within 60 minutes of the dose and reduction of total daily off times, and led to improved Patient Global Impression of Change scores in 75% of patients, which reflects the patients’ assessment of treatment effectiveness.

“In the clinical study program, Inbrija established its safety profile and demonstrated clinically meaningful improvements in motor function,” said Robert A. Hauser, MD, a professor of neurology and director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida. “Inbrija helps address a significant unmet need for people with Parkinson’s, and we look forward to adding this new treatment option to our armamentarium.”

Inbrija is not to be used by patients currently on or treated with a nonselective monoamine oxidase inhibitor, such as the antidepressants and anxiolytics phenelzine or tranylcypromine, within the last two weeks.

The company is currently seeking EU approval for Inbrija.

Burkhard Blank, MD, Acorda’s chief medical officer, said he was “delighted” with Inbrija’s approval and its upcoming availability for on-demand use, based on each patient’s needs.

“We thank the FDA for a constructive dialogue throughout the development program and their partnership during the review cycle. We especially thank all those who volunteered for the Inbrija clinical trials, without whose commitment new medications could not be developed,” he said.

He further noted the important role played by “people living with Parkinson’s, their care partners, researchers, clinicians and advocacy groups,” to achieve FDA approval.

A webcast of a recent conference call hosted by Acorda is available here.

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New Art Initiative Aims to Improve Understanding and Discussion of Parkinson’s Off Periods

art initiative, off periods

A new initiative by Acorda Therapeutics uses art to help people with Parkinson’s disease recognize and communicate about their off-period experiences.

The initiative, called Framing OFF Through Art, builds on Acorda’s Live Well. Do Tell program, launched earlier this year.

Framing OFF Through Art includes artwork inspired by the experiences of patients with Parkinson’s and their caregivers. The artists who created the pieces also have personal connections to the disease. Each artist partnered with two patients and their caregivers. The art aims to educate and encourage others with Parkinson’s and their care partners to identify off-period symptoms and discuss them with their healthcare professionals.

“Art is a powerful way to engage a community, and in Framing OFF Through Art, our goal is to create an emotional connection that results in better dialogues about Parkinson’s symptoms,” Ron Cohen, MD, Acorda’s president and CEO, said in a press release.

The artwork debuted on Oct. 23 at an event in New York, where the artists, patients, and their caregivers were guests. The first piece was created by Julie B., whose mom is living with the disease, and is available on the Live Well. Do Tell website. More art and personal stories will be revealed each month.

“I know that some of these symptoms are really difficult to put into words. A visual representation can really communicate what you are going through,” Julie B. said in a video interview. “One of the big takeaways from this initiative is the idea of an open and honest conversation.”

Off periods are a common complication in Parkinson’s patients, characterized by the return of motor and non-motor symptoms — such as anxiety and sadness — when levodopa’s effects wear off. The need to better understand off periods, as well as how to talk with others about them, had been originally highlighted in the Live Well. Do Tell statement of need.

This report was the first output of the campaign, and includes six actions for the Parkinson’s community: tailor resources at diagnosis; broaden the Parkinson’s community’s ability to identify off periods; educate about motor fluctuations and how they do not necessarily mean disease progression; identify opportunities for caregivers to discuss their experiences with healthcare professionals; enhance the patient-clinician dialogue; and improve clinical practice via insights from movement disorder specialists and a new tool to measure off periods.

The report was based on insights from the campaign’s steering committee meeting that included Parkinson’s community leaders. Others may join the conversation by signing up for initiative updates and news.

“Off periods can be frustrating and challenging, as symptoms are varied and often difficult for patients to communicate effectively to their care providers,” said Matthew Stern, MD, director emeritus of the Parkinson’s Disease and Movement Disorders Center at Penn Medicine.

“By helping people with Parkinson’s understand how to verbalize what they are experiencing, we, as their healthcare providers, can better understand their needs and help them achieve a better sense of well-being,” added Stern, who is the chair of the Live Well. Do Tell steering committee.

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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

Opicapone Superior to Comtan in Providing Motor Benefits to Parkinson’s Patients, Phase 3 Study Shows

opicapone

Once-daily treatment with opicapone provides continued reductions of off periods in Parkinson’s patients taking levodopa, Neurocrine Biosciences’ Phase 3 clinical study shows.

The findings also reveal that opicapone’s effectiveness was superior to that of Comtan (entacapone, marketed by Novartis).

The results were presented in three scientific posters at the 2018 World Congress on Parkinson’s Disease and Related Disorders (IAPRD), taking place in Lyon, France.

Opicapone is designed as a once-daily add-on therapy to levodopa for adults with Parkinson’s and end-of-dose motor fluctuations. It is an inhibitor of the enzyme catechol-o-methyltransferase, or COMT, which breaks down levodopa. This leads to prolonged levodopa effects, as it reduces the time when the medication wears off before the next dose — s0-called off periods.

It is currently marketed in Europe as Ongentys. The company is intending to start the U.S. regulatory review in early 2019, which could lead to the medication’s approval.

“Neurocrine Biosciences is committed to bringing innovative and effective treatments to patients living with movement disorders,” Eiry W. Roberts, MD, Neurocrine’s chief medical officer, said in a press release. Roberts added that these findings will help healthcare providers further understand “the potential of opicapone to help [Parkinson’s] patients.”

Neurocrine compared the effectiveness and safety of 5, 25 and 50 mg doses of opicapone over a three-week treatment to that of 200 mg of Comtan (also a COMT inhibitor) and placebo. Primary results from BIPARK I as well as data from its open-label extension phase already had been published.

The multi-center, double-blind Phase 3 study (NCT01568073) included patients 30 to 83 years old, with a three-year diagnosis of idiopathic Parkinson’s, Hoehn and Yahr (H-Y) stage — a system used to assess the worsening of Parkinson’s symptoms — of 1 to 3 (meaning minimal or no functional disability, to mild-to-moderate disability), and receiving treatment with levodopa for at least one year.

In the study, “Efficacy of Opicapone in Parkinson’s Disease Patients with Motor Fluctuations: A Phase III, Randomized, Double-Blind, Placebo- and Active-Controlled Study – BIPARK I,” researchers analyzed data from 590 patients — 119 taking 5 mg of opicapone, 116 receiving 25 mg, 115 taking 50 mg, 120 on 200 mg Comtan, and 120 on placebo.

Results showed that both 50 mg opicapone and Comtan significantly decreased the duration of daily off periods and increased “on time” (periods when symptoms are controlled) without troublesome dyskinesia, which are involuntary, jerky movements. However, the higher dose of opicapone led to a 51% greater reduction in off periods (50.8 minutes vs. 40.3 minutes).

The data further revealed that, unlike Comtan, 50 mg opicapone was associated with significant improvement in the proportion of both off and on responders (minimum of one hour improvement) compared to placebo. Also, unlike Comtan and placebo, opicapone led to favorable ratings in both Patient Global Impression of Change (PGI-C) and Clinical Global Impression of Change (CGI-C).

This was further addressed in the study, “Opicapone as Adjunctive Therapy to Levodopa in Patients with Parkinson’s Disease and Motor Fluctuations: Global Impressions of Change Compared to Placebo and Entacapone,” which reported that, for PGI-C, the proportion of patients reporting improvement ranged between 63.8% to 72.2% for opicapone groups, vs. 50.8% for placebo, and 52.5% for Comtan.

As for CGI-C, the proportion of patients assessed as improved ranged between 60.3% to 73.0% for opicapone, in comparison to 50.0% for placebo and 50.8% for Comtan.

Treatment-emergent adverse events (TEAEs) were reported by 51.6%-54.6% of patients taking opicapone, 56.6% on Comtan, and 49.6% on placebo.

Compared to placebo, opicapone led to more common dyskinesia, insomnia, and dizziness. TEAEs were similar between opicapone and Comtan.

“[Opicapone] 50 mg once-daily was effective in the treatment of motor fluctuations with a favorable profile compared to [Comtan],” researchers wrote.

The study, “Switch of Double-Blind Opicapone, Entacapone, or Placebo to Open-Label Opicapone: Efficacy Results of the 1-Year Extension of Study BIPARK I,” reported the efficacy results of a one-year extension study of BIPARK I. This trial included patients who completed BIPARK I or the Phase 3 study BIPARK II (NCT01227655).

All patients included in study began with a 25 mg dose of opicapone for a minimum of one week, regardless of prior double-blind treatment.

Compared to the start of the trial (baseline), mean off time was reduced by 34 minutes. If comparing to the start of BIPARK I, this represented a decrease superior to two hours (127 minutes).

Opicapone reduced off periods by 65 minutes and 39 minutes and increased on periods without troublesome dyskinesia by 43 minutes and 46 minutes, when compared to BIPARK I participants’ taking placebo or Comtan, respectively.

Overall, opicapone “maintained its efficacy over the 1-year treatment period,” researchers wrote.

The medication was originally developed by Portugal-based BIAL, which licensed the North American rights to Neurocrine in February 2017.

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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

#AAN2018- Inbrija Reduces Parkinson’s Off Periods, Phase 3 Trial Shows

Phase 3 Inbrija trial

Inbrija reduces Parkinson’s symptoms when standard treatments wear off, and decreases the length of these off periods, a Phase 3 clinical trial shows.

The therapy’s developer, Acorda Therapeutics, will present the results at the American Academy of Neurology annual meeting in Los Angeles, April 21-27. Parkinson’s News Today will be covering the conference.

Acorda’s presentation will be at 4:54 p.m. Pacific time on Tuesday, April 24. The title will be “Long-term Efficacy of Inhaled Levodopa in Parkinson’s Disease Subjects With Motor Fluctuations: a Phase 3 Open-Label Randomized Study.”

Inbrija (CVT-301) is a self-administered, inhaled version of levodopa intended to reduce the time when standard levodopa treatment wears off — periods known as off times.

Acorda conducted the Phase 3 trial (NCT02352363) to evaluate the safety and effectiveness of an 84-mg dose of Inbrija over 12 months in 408 Parkinson’s patients with movement problems.

The Inbrija group consisted of 278 patients. The other 130 were assigned to standard care. Only 204 of the patients who received Inbrija were able to complete the trial.

At the beginning of the study, the Inbrija group had a mean age of 63.6 years, had had Parkinson’s for nine years, were averaging 3.6 off periods a day, and were experiencing total off times of 5.6 hours per day. Patients took an average of 2.3 doses of Inbrija a day.

One of the measures that researchers used to measure Inbrija’s effectiveness was improvements in patients’ UPDRS-III scores, which assess both movement and non-movement symptoms, 10, 20, 30, and 60 minutes after dosing. Another measure was the percentage of patients able to regain control of their symptoms within 60 minutes of treatment.

Still another measure was reductions in patients’ off times. And a fourth was better scores on a scale known as PGIC, which shows whether a patient believes a treatment is effective.

A key finding was improvements in Parkinson’s symptoms at all time points between week 4 and 52 on the UPDRS-III scale.

Another finding was that patients were able to regain control of their symptoms within 60 minutes.

In addition, patients were able to reduced their total daily off times by between 1.32 and 1.42 hours. And 75 percent of patients showed improvements in PGIC scores.

Overall, improvements in UPDRS-III scores, daily off times and PGIC scores “support the efficacy of up to 52 weeks of treatment with CVT-301 (Inbrija) 84 mg in the treatment of off period symptoms,” the researchers wrote.

The results prompted Acorda to seek European Union approval of Inbrija as a treatment for off periods in Parkinson’s.

In addition to data from this Phase 3 trial, Acorda’s application to the EU included results of the Phase 3 SPAN-PD trial (NCT02240030) in 351 participants and the Phase 3 CVT-301-004E trial (NCT02242487) in 325 participants.

The U.S. Food and Drug Administration accepted Acorda’s New Drug Application for Inbrija in February 2018. It is expected to decide whether to approve it by October 5.

The post #AAN2018- Inbrija Reduces Parkinson’s Off Periods, Phase 3 Trial Shows appeared first on Parkinson’s News Today.

Source: Parkinson's News Today