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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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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.

The post Inbrija Approved in US to Treat Off Periods in Parkinson’s Patients on Carbidopa/Levodopa appeared first on 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.

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Source: Parkinson's News Today

Acorda Asks European Union to Approve Inbrija for Parkinson’s Off Periods

Inbrija approval request

Acorda Therapeutics has asked the European Medicines Agency to approve Inbrija (CVT-301) to reduce the periods when the standard Parkinson’s treatment carbidopa/levodopa is not working.

Inbrija is a self-administered, inhaled levodopa therapy. Acorda developed it to reduce the time when standard levodopa treatment wears off — periods known as off times.

Both movement and non-movement symptoms return during off times. About half of  patients taking standard levodopa have off periods, which become more frequent and severe during the course of the disease.

Inbrija was designed to deliver a precise dose of a dry powder form of levodopa to patients’ brains. The powder form bypasses the digestive system, preventing delays in the medication kicking in.

Acorda filed a marketing authorization application asking the European Union to approve the therapy. The application included results from its 12-week Phase 3 SPAN-PD clinical trial (NCT02240030). The study assessed the safety and effectiveness of 84-mg and 60-mg doses of Inbrija’s administered up to five times a day in 351 Parkinson’s patients experiencing off periods.

Inbrija improved patients’ movement in comparison with a placebo, results showed.

In line with a previous Phase 2b trial, researchers found no lung safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Acorda presented the SPAN-PD results at the International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, Canada, in June 2017.

The application included the results of two long-term Phase 3 safety trials as well. The CVT-301-005 trial (NCT02352363) covered 408 patients, and the CVT-301-004E study (NCT02242487) 325 participants.

Researchers found no changes in the treated patients’ lung function, compared with standard levodopa treatment. Taken together, the findings indicated that Inbrija was safe as an off-period treatment, Acorda said.

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

U.S. regulators refused to accept Acord’s initial application due to concerns over the manufacturing of Inbrija. The company addressed the questions in a revised application.

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

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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