Equfina, Known as Xadago in US, Approved in S. Korea as Levodopa Add-on

therapy approval

Equfina (safinamide) has been approved in South Korea as an add-on therapy to levodopa for Parkinson’s disease patients who experience “off” episodes, Eisai, which is marketing this medication in parts of Asia, announced.

The approval makes South Korea the first country in Asia outside of Japan to sell Equfina.

Under the brand name Xadago, the add-on therapy was approved for the same indication in Europe in 2015 and in the U.S. in 2017. In Canada it is marketed under the name Onstryv.

“Off” periods in Parkinson’s are characterized by the reappearance or worsening of motor symptoms — such as tremors and dyskinesia (involuntary movements) — due to a gradual decline in levodopa’s effectiveness throughout the day.

Safinamide, developed by Newron Pharmaceuticals, increases the level and function of dopamine — the neurotransmitter, or signaling molecule, missing in those with Parkinson’s — in the brain. It does so by inhibiting the enzyme monoamine oxidase B that normally breaks down dopamine, and also by inhibiting (blocking) transporters that are responsible for its uptake, meaning its absorption and retention.

Safinamide also inhibits an excessive release of the neurotransmitter glutamate.

Equfina’s approval in South Korea was based on clinical results from the SETTLE Phase 3 study (NCT00627640). The global trial enrolled 549 patients experiencing off episodes while on a stable regimen of levodopa plus benserazide or Lodosyn (carbidopa).

Participants were randomized to either oral safinamide (50 mg per day, increased to 100 mg per day if tolerated) or a placebo as an add-on therapy for 24 weeks.

The study’s main goal was changes in mean daily “on” time (the period in which motor symptoms are efficiently controlled) about six months of treatment or placebo use.

Results showed that adding safinamide to levodopa significantly increased the length of “on” periods without dyskinesia by almost one hour (57.6 minutes) compared with placebo.

Adverse treatment reactions were seen in 28.5% of patients in the safinamide group and in 27.6% of those given a placebo, with the most frequent including dyskinesia, nausea, and somnolence (sleepiness).

Newron entered a licensing agreement with Meiji in 2011, granting the company exclusive rights to manufacture and commercialize safinamide in Asia. Based on a licensing agreement between Eisai and Meiji, Eisai now has exclusive rights for developing and marketing safinamide in much of Asia.

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Supernus Acquires Apokyn and Xadago from US WorldMeds

acquisition news

Supernus Pharmaceuticals’ acquisition of US WorldMeds’ portfolio of central nervous system (CNS) disease treatments adds two established Parkinson’s disease (PD) therapies and a leading investigative product to its neurology portfolio.

The deal calls for a $300 million upfront cash outlay, plus $230 million in milestone payments for the Parkinson’s treatments Apokyn (apomorphine) and Xadago (safinamide).

Supernus also acquired the company’s Apomorphine Infusion Pump, which, if approved by the U.S. Food and Drug Administration (FDA), would allow for a continuous subcutaneous (under the skin) apomorphine infusion.

“This acquisition aligns extremely well with our strategy of expanding and enhancing our commercial and late-stage assets and is a significant step in strengthening our leadership position in CNS,” Jack Khattar, Supernus’ president and CEO, said in a press release.

It also “brings new research and development platforms to Supernus in biologics and medical devices. We look forward to building on the success that US WorldMeds had in establishing this portfolio of unique products.”

Apokyn is given by injection between doses of the levodopa to treat a loss of body movement control in patients with advanced Parkinson’s. It has the same effect as dopamine, a naturally occurring chemical messenger in the brain that is gradually lost in the disease.

Several years after starting levodopa — a gold standard in care — most patients begin experiencing motor symptom fluctuations 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 daily. In a Michael J. Fox Foundation survey of 3,000 patients, more than 90 percent reported having at least one “off” episode daily, and nearly 65 percent experienced such episodes for at least two hours.

Apokyn does not prevent off episodes, but it does help to improve symptoms when an episode has begun.

Xadago is an oral once-daily add-on therapy developed to improve motor function in Parkinson’s patients experiencing off periods. It works through the selective and reversible inhibition of the enzyme monoamine oxidase B, which increases functional dopamine levels. It also blocks voltage-dependent sodium channels, which regulate the release of abnormal glutamate, a neurotransmitter in the brain involved in nerve cell communication. The treatment is available in several countries, including the United States.

If approved by the FDA, the Apomorphine Infusion Pump would offer Parkinson’s patients a less-invasive and more convenient way to administer Apokyn. The device would provide a continuous subcutaneous infusion of the medication.

Supernus is expected to submit an application to the FDA requesting approval this year, likely supported by findings in a Phase 3 trial of the pump’s use (NCT02339064) in patients. If approved, the product could launch in the second half of 2021.

“The core values of Supernus align very well with US WorldMeds,” said Paul Breckinridge Jones Sr., CEO of US WorldMeds. “We expect a seamless transition with even more patients benefiting from these products under Supernus’ stewardship. This transaction will allow US WorldMeds to focus on growing our other exciting business units.”

This CNS portfolio, which includes the cervical dystonia therapy Myobloc (rimabotulinumtoxinB), had net sales last year of about $150 million. Under the agreement, Supernus will also gain a sales team with expertise in serving movement disorder specialists in the U.S.

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Top 10 Parkinson’s Stories of 2018

Top 10, Parkinson's

Parkinson’s News Today provided you with daily coverage of important findings, treatment developments, and clinical trials related to Parkinson’s during 2018.

We look forward to bringing more news to Parkinson’s patients, as well as their family members and caregivers, during 2019.

Here are the Top 10 most-read articles of 2018, with a brief description of what made them interesting to the Parkinson’s community.

 No. 10 – “Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

Results of a Phase 2 trial (NCT02954978) of Novartis’ nilotinib in 75 patients with mid-stage Parkinson’s and mild cognitive impairment suggested the therapy increased production and metabolism of dopamine within one to four hours after a single treatment. Also, low-dose nilotinib (150 mg and 200 mg) — marketed as Tasigna for certain types of leukemia — was associated with lower levels of an altered and toxic form of alpha-synuclein, the main component of Parkinson’s hallmark protein clumps known as Lewy bodies.

No. 9 – “Potential Parkinson’s Vaccine, Affitope PD01A, Safe and Possibly Effective in Long-term, Phase 1 Trial Series Finds

The long-term safety, tolerability, and immune response associated with an experimental vaccine called Affitope PD01A were studied in a series of four consecutive Phase 1 trials: AFF008 (NCT01568099), AFF008E (NCT01885494), AFF008A (NCT02216188), and AFF008AA (NCT02618941). Twenty-one treated and five control patients completed the series. The results showed that both 15 μg or 75 μg doses of Affitope were well-tolerated, only causing mild injection-site reactions. The vaccine, being developed by Affiris, induced a clear immune response against its target — alpha-synuclein — that was stabilized with “boost” injections. At week 26 of treatment, it induced a trend toward lower levels of a toxic form of alpha-synuclein in the blood and cerebrospinal fluid, the liquid surrounding the brain and the spinal cord.

No.8 – “MRI-Focused Ultrasound Undergoing Phase 3 Clinical Trial for Parkinson’s Treatment

A Phase 3 trial (NCT03319485) of a potential nonsurgical treatment, known as magnetic resonance imaging (MRI)-guided focused ultrasound, also attracted significant interest. The InSightec-sponsored study — still recruiting patients with advanced disease — is exploring the procedure’s safety and effectiveness. It follows a pilot trial demonstrating lesser upper-limb tremors in patients with tremor-dominant Parkinson’s who did not respond to other therapies. In this non-invasive approach, ultrasound waves destroy damaged tissue in a brain structure called the globus pallidus, which is involved in the regulation of voluntary movement. The team expects to enroll 80 to 100 participants.

No. 7 – “Key to Effective Parkinson’s Treatment May Lie in Stem Cells, Researchers Say

Advancements in stem cell therapy for Parkinson’s were also of clear interest to our readers. Two articles assessed the replacement of dopamine-producing neurons, progressively lost during the course of disease. The first focused on patient-derived induced pluripotent stem cells (iPSCs), fully matured cells that researchers are able to reprogram in vitro (in the laboratory) to revert them to a stem cell state in which they are able to grow into any type of cell, including dopaminergic nerve cells. The second study focused on an alternative approach to stem cell therapy that, instead of iPSCs, uses parthenogenetic-derived neural stem cells. These cells are obtained by chemical manipulations in unfertilized human oocytes, or immature egg cells, which are also able to grow into neurons. A Phase 1 trial (NCT02452723) of this approach is underway in patients with moderate to severe disease at a single site in Australia.

No. 6  “Psychosis in Parkinson’s Linked to Volume Changes in Specific Area of Brain, Study Says

Atrophy, or shrinkage, of the hippocampus — a critical brain area involved in memory — correlates with psychosis in patients with Parkinson’s disease. Specifically, researchers found that the volume of distinct subzones of the hippocampus was associated with psychosis severity and impaired cognitive functions. Greater volume was also seen in another specific brain area, the hippocampal fissure, and seems to correlate with poorer visual memory and visuospatial functions. Previous data had suggested that change in this area is a radiological hallmark of ongoing brain atrophy in the hippocampus.

No. 5 – Tiny Brain Bleeds Associated with Parkinson’s Disease Dementia, Study Reports

The link between tiny bleeds in the brain — cerebral microbleeds (CBMs) — with both cognitive impairment in Parkinson’s disease and risk of associated dementia was No. 5 among the year’s most-read stories. CBMs are small (2-10 mm as assessed by MRI), chronic brain hemorrhages believed to be caused by structural abnormalities of the brain’s small vessels. Scientists found that CBMs were more common in Parkinson’s patients with dementia than in those without dementia, and were associated with lower cognitive scores. Other findings showed that patients with CBMs were older, and had more severe Parkinson’s symptoms and cerebrovascular lesions.

No. 4 – “Vitamin B12 Supplements May Help Slow Parkinson’s Progression, Study Finds

Patients at early stages of Parkinson’s with low levels of vitamin B12 may experience faster motor and cognitive decline. Prior work had shown that B12 deficiencies can induce neurological and motor symptoms associated with Parkinson’s, including depression, paranoia, muscular numbness, and weakness. This study differed in that it was conducted in untreated patients earlier in the disease course, and found slower progression in those taking a multivitamin supplement. Overall, the findings suggest that vitamin supplements may help slow symptom progression.

No. 3  “Xadago, Cannabinoids, Opioids May Be Best to Manage Parkinson’s Pain, Review Suggest

Pain is a frequent non-motor symptom of Parkinson’s disease. A review study found that its management may be most effective with Xadago (safinamide, by US WorldMeds) or with cannabinoids and opioids.  Other approaches, such as multidisciplinary team care, Comtan (entacapone) and Tasmar (tolcapone) may also provide pain relief. In turn, the investigational treatment pardoprunox (SLV-308) and surgery reported only moderate benefits on reducing pain severity.

No. 2 – “Medical Cannabis Helps Older People with Parkinson’s, Other Diseases, Study Finds

Medical cannabis is a safe and effective option to ease pain in older patients with Parkinson’s, cancer, or other illnesses. In a study involving 2,736 people 65  years or older, its use over six months enabled a reduction or discontinuation of opioid pain medications in over 18% of patients. Participants also reported an improved quality of life. The most common adverse events were dizziness and dry mouth, reported by 7.1% of patients.

No. 1 – “Vitamin B3 Compound May Prevent Motor Decline in Parkinson’s Disease, Study Says

Out most widely read article of 2018 reported that a form of vitamin B3 — nicotinamide riboside — prevented the loss of motor function and lessened nerve cell death in a fly model of Parkinson’s. It also increased the levels of a metabolic compound called NAD+ and improved energy balance in fish neurons with a defective GBA gene — the most frequent gene risk for Parkinson’s — and defects in mitochondria, the cell’s powerhouse. The researchers suggested that this form of vitamin B3 may help treat impaired mitochondria function, which has been linked to Parkinson’s development.


At Parkinson’s News Today, we hope that these articles,  along our continuing reporting throughout 2019, help to educate, inform, and improve the lives of patients and their loved ones.

We wish all our readers a happy 2019.


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Xadago, Cannabinoids, Opioids May Be Best to Manage Parkinson’s Pain, Review Suggests

pain management

Treatment with Xadago (safinamide) or cannabinoids and opioids may the best therapeutic options to effectively manage pain in patients with Parkinson’s disease, researchers suggest.

The study, “Comprehensive Examination of Therapies for Pain in Parkinson’s Disease: A Systematic Review and Meta-Analysis,” was published in the journal Neuroepidemiology.

Parkinson’s disease is known mostly for its motor symptoms such as muscle rigidity and tremors, but other non-motor symptoms are very common. About 68-95% of Parkinson’s patients suffer with pain, which can significantly affect their quality of life and promote both depression and anxiety.

There are several therapeutic strategies available for Parkinson’s disease, however their potential to manage disease-associated pain is not established.

Parkinson’s Clinic of Eastern Toronto researchers reviewed available data from 24 published reports to explore current treatments’ capacities for pain relief. The reports covered the results of 25 randomized clinical trials and a total of 1,744 patients undergoing therapeutic interventions and 1,610 patients undergoing a control intervention.

The mean age of study participants was 66 years and most were male (61% and 60% in treatment or control groups, respectively). Mean disease duration was of 7.9 in the treatment group, and 7.2 years in the control group.

The treatment with the biggest capacity to reduce pain severity was Xadago, followed by cannabinoids and opioids, multidisciplinary team care and COMT inhibitors, such as Comtan (entacapone) and Tasmar (tolcapone).

Electrical and Chinese therapies also had some capacity to reduce pain, although results between studies were very heterogeneous.

Treatment with the investigative pardoprunox (SLV-308) and surgery had only moderate effect on reducing pain severity, while the weakest effects were in dopaminergic agonists and miscellaneous therapies.

Collectively these findings revealed that Xadago “is an important adjunct to the standard parkinsonian medications for alleviating pain” in Parkinson’s, while analgesics in the form of opioids and cannabinoids can “be effective but not nearly to the same extent,” researchers wrote.

In addition, the team believes this study shows that adjusting levodopa levels with Comtan rather than with dopaminergic therapies may provide greater pain relief.

Still, additional trials focusing on pain management, as well as in its underlying mechanisms in Parkinson’s patients, are warranted to “form a consensus on the effectiveness of these therapies.”

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Source: Parkinson's News Today