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Lobsor Pharmaceuticals Plans to Enter the U.S. Market with Treatment for Advanced Parkinson’s

Lecigon U.S. patent

The United States Patent and Trademark Office (USPTO) has approved a patent covering the composition and method of administration of a new levodopa replacement formulation for treating Parkinson’s disease.

Lecigon was developed by Lobsor Pharmaceuticals to be the next-generation of Stalevo (marketed by Novartis), a widely used oral therapy for earlier stages of Parkinson’s disease. It consists of a gel containing a fixed combination of levodopa, carbidopa, and entacapone that should be administrated through continuous intestinal infusion with an easy-to-use pump.

This novel treatment was approved in October 2018 by the Swedish Medical Products Agency (MPA).

With the newly granted U.S. patent (10,071,069), Lobsor is taking the first steps to introduce Lecigon in the U.S. market for treating symptomatic advanced Parkinson’s disease through the company’s partner, Intrance Medical Systems.

“We are delighted to receive this new patent to further protect our treatment system,” Roger Bolsöy, Lobsor’s CEO, said in a press release. “With the new formulation and lightweight delivery pump, we believe Lecigon will significantly improve convenience and quality of life for Parkinson’s patients.”

Lecigon combines the beneficial effects of the dopamine replacement compound levopoda with two modulators of dopamine metabolism. This particular combination is expected to increase and prolong brain exposure to levopoda, while reducing the risks of dopamine-related adverse reactions in other body parts.

Administration of Lecigon into the small intestine through a small and accurate pump makes it possible to overcome some of the limitations of treatment with levodopa, such as its reduced blood stability.

“Improving bioavailability and achieving a similar clinical outcome with significantly lower levodopa doses means we can also report significant reductions in 3-OMD, a metabolite in a metabolic complex associated with long term side effects of levodopa,” Bolsöy said.

The U.S. patent covers not only the composition of Lecigon, but also the method of preparing the therapeutic suspension and how to use it to treat patients. Patent claims are not limited to any compounds amounts, which protects Lobsor’s rights on the broad and tailored use of Lecigon, according to Parkinson’s patients’ needs.

The patent will expire in September 2035 and a corresponding patent is currently active in Sweden. Lobsor has pending patent requests for Lecigon in Europe, Australia, Canada, China, and Japan.

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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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Back to Medications

medications

Haven’t I been here before?

I can’t fight this alone. Medications are now an option.

Several months on a holistic route gave me no improvement in symptoms. So, I bit the bullet and decided to try another Parkinson’s prescription medication.

In October 2017, I started the Neupro (rotigotine) transdermal patch. This bypasses the digestive system (hence, less chance of nausea) because the medicine absorbs through the skin. The 8-mg dosage made me dizzy, so the doctor dropped me to 6 mg. I had no dizziness, but I also had no relief from symptoms. In December 2017, I agreed to try carbidopa-levodopa (the generic version of the “gold” standard therapy for treating PD). Unfortunately, the generic medication plagued me with nausea and dizziness.

In January 2018, I appealed to my insurance company to cover the brand name version of the medication — Sinemet 25 mg/100 mg.  The doctor gave me a titration schedule to ease me into the medication. By February 2018, I was using a 6-mg Neupro patch per day and taking two Sinemet tablets three times a day. My “internal tremors” subsided and my second-left toe no longer curled. Unfortunately, this was not an “aha” moment; the change was very subtle.

Almost three years since diagnosis, I’m still putzing around.

My goal is to minimize my reliance on medications, as the long-term effects are not good (there is a risk of dyskinesia from using Sinemet). This is a classic case of a medication having a side effect that is also a symptom of the disease the medication is attempting to alleviate. In March 2018, my doctor agreed that I could cut back the Neupro dosage to 1 mg a day. This medication is cost prohibitive. Even with insurance, I pay over $200 per month.

Applying the patch to a different part of the body daily every 14 days is cumbersome. However, by the time I got to a 1-mg dosage, I had overwhelming fatigue, some depression, and general weakness. By the end of April, I had gone back to 2 mg of Neupro (while continuing with Sinemet). This change seemed to help my fatigue somewhat, but not enough for me to function well.

In mid-May, my doctor suggested I try a daily 3-mg patch of Neupro. This was very discouraging for me, as I want to take the minimum medications that will allow me to feel good enough to do the exercise I need to do to slow Parkinson’s progression and provide symptom relief. I want to decrease my reliance on prescription medications, not increase them.

What about exercise?

We walk a fine line when it comes to exercise. We need to push our intensity. However, if we get injured and can’t exercise, we lose the benefits of what movement does for our quality of life. Sometimes I wonder if I will exhaust my dopamine allotment for the day if I push myself too hard. Now, when I overdo my exercise, I am usually wasted for the rest of the day. As a former dancer and cyclist, it has always been in my nature to push my limits, and it is a tough habit to break.

To add to my confusion, I’ve read articles about how intense exercise is great for those with Parkinson’s. Exercising three times weekly at high intensity — 80 to 85 percent of maximum heart rate — is not an easy task, especially when plagued with symptoms of apathy, fatigue, and lack of motivation. As a former Spinning instructor, when I heard cycling is great for Parkinson’s patients, I was ecstatic. Piece of cake, I said to myself. However, the recommendation was to pedal at 80 to 90 rpms for 45 minutes, three times per week, a challenge even without Parkinson’s.

Cycling is great for Parkinson’s patients. (Courtesy of Jean Mellano)

In Greek mythology, Sisyphus was condemned to an eternity of rolling a boulder uphill to watch it roll back down again. At times, I feel like a modern-day Sisyphus when I exercise. It feels like a fruitless task that has no ending and is impossible to complete.

Do I still need to take prescription medications?

I am continuing to adjust my medications to find that Holy Grail combination that will hopefully make me feel more like my former self. I will take my supplements, attempt to reduce my stress where possible, maintain a healthy vegan diet, exercise, and meditate. Because I am trying so many things to improve my situation, it will be very difficult to know what is working for me and what is not.

In my next column, I will share with you what I believe has helped me the most.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Source: Parkinson's News Today

Duopa Can Help Parkinson’s Patients Manage Impulse Control Disorders, Study Shows

Duopa for impulse control

AbbVie’s Duopa can reduce impulse control disorders in patients with advanced Parkinson’s disease and mild-to-moderate neuropsychiatric problems, a study shows.

The research, “Improvement of impulse control disorders associated with levodopa-carbidopa intestinal gel treatment in advanced Parkinson’s disease,” was published in the Journal of Neurology.

Parkinson’s disease is characterized by the death of brain cells that produce the signaling molecule dopamine — a chemical that facilitates communication between nerve cells.

Dopamine replacement agents can reduce movement symptoms of the disease. The treatments can lead to side effects, however. One is impulse control disorders, such as compulsive gambling, buying, sexual behavior, and eating.

Duopa is an intestinal gel formulation of the carbidopa-levodopa combo that AbbVie developed to help manage Parkinson’s symptoms. It reduces the time when standard levodopa treatment wears off — periods known as off times.

Little is known about its non-movement side effects, however.

Spanish researchers wanted to know if Duopa would increase impulse control disorders in Parkinson’s patients. Their study involved 62 patients with an advanced form of the disease who received Duopa for six months. The patients had had symptoms a median of 13.5 years and movement problems a median of five years.

Duopa reduced patients’ off periods by almost six hours a day, or 79 percent. It failed to reduce the duration of patients’ uncontrolled movements, however. Duopa also improved patients’ ability to perform daily activities. In general, the treatment reduced the severity of the disease’s symptoms by 25 percent.

The treatment also led to signficant improvements in patients’ scores on an impulse control disorder index known as the Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s disease. Patients’ scores fell by 54 percent over three months and by 64 percent over six months.

In terms of type of disorder, there were significant reductions in compulsive eating, in taking medication compulsively, in becoming compulsive hobby enthusiasts, and in compulsive punding, or engaging in repetitive mechanical tasks like assembling and disassembling things.

In contrast, Duopa led to no changes in compulsive gambling, sex, or buying.

Another finding was that the therapy led to significant reductions in psychosis, improved sleep quality and better social interactions.

“Currently, there is no consensus regarding treatment of impulse control disorders,” the researchers wrote. Key reasons are the variability of impulsive behavior symptoms and lack of clinical trials addressing the issue, they said.

As a whole, the study indicated that Duopa could be a good way to help people with advanced Parkinson’s disease manage their impulse control disorders.

Importantly, Duopa can significantly improve patients’ movement symptoms and sleep quality without a significant increase in levodopa dosage, the researchers wrote.

But additional studies are necessary to compare Duopa’s impact with that of other commonly used Parkinson’s treatment, the team added.

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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