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EAN Congress Blog

Access daily, concise peer-reviewed reports from the EAN Congress selected by the Neurology Today editors.

Thursday, June 21, 2018

​BY ED SUSMAN​

LISBON, Portugal—The investigative agent lasmiditan relieves patients' most bothersome migraine symptoms within two hours of dosing, researchers reported here at the Congress of the European Academy of Neurology.

The so-called SPARTAN study was the second of two pivotal phase 3 trials evaluating lasmiditan in migraine patients with and without aura. In the large phase 3 trial, 48.7 percent of the 528 patients assigned to the 200 mg dose of lasmiditan in the modified intent-to-treat analysis said they were free of their most bothersome migraine symptom — usually light sensitivity — at two hours, compared with 33.5 percent of 540 placebo patients (p<0.001).

The study participants averaged five or more migraine attacks a month during the previous three months. About 37 percent had migraines accompanied by aura, about 18 percent used prophylactic medication to prevent migraine attacks, and on average they had migraines for 18 years. More than 75 percent of the patients had at least one cardiovascular risk factor.

“Higher doses of lasmiditan separated from placebo as early as one hour for pain-free achievement and within 30 minutes for relief of the most bothersome symptom,” reported Sheena Aurora, MD, medical fellow and launch leader on the pain team for Lilly Bio-Medicines of Eli Lilly and Company in Indianapolis.

About 38.8 percent of patients taking the 200 mg dose of lasmiditan achieved pain-free status within two hours compared with 21.3 percent of patients on placebo (p<0.001), she said.

Among other findings, 31.4 percent of patients on the 100 mg dose of the dose also achieved the pain-free milestone in two hours, which was also significantly superior to placebo (p<0.001); 28.8 percent of patients on the 50 mg dose were free of pain at two hours (p=0.03), Dr. Aurora said in her oral presentation.

Dr. Aurora said the drug was generally well tolerated. Most common side effects were dizziness, paresthesias, and somnolence, she noted.

Dr. Aurora added that the company was planning to file a new drug application for lasmiditan by the end of 2018.

Commenting on the study, Noah Rosen, MD, director of Northwell Health's Headache Center in Great Neck, NY, told the Neurology Today Conference Reporter: “Up until now, the only migraine specific acute medications we have had have been the triptans, which block 5HT1b and d receptors. Even then they are not truly migraine specific as other conditions, such as cluster headache, which also respond to their use.”

“While triptans are arguably the most important leap forward in the 20th century with regards to the management of migraine, they also have significant limitations,” he said. “These include the relative contraindications of coronary artery disease, cerebrovascular disease, and peripheral vascular disease.”

“The advent of lasmiditan, which preferentially affects the 5HT1f receptor, should, in theory, be less of a cardiovascular risk as that receptor is not represented on salient blood vessels,” he said, disclosing that he has consulted for Eli Lilly although he was not a participant in the current trial. “As such, lasmiditan may not only be as effective as a triptan, but also less of a questionable risk in people with known risk factors for cardiovascular disease.”

He said that when approved lasmiditan will “expand our armamentarium for the acute treatment of migraine. It is often the case that individuals can’t tolerate medications either due to side effects or a lack of efficacy.” 

“Having this medication allows us other opportunities to manage migraines in that refractory population,” Dr. Rosen said.

Thursday, June 21, 2018

BY ED SUSMAN


LISBON, Portugal—Patients with Alzheimer’s disease and progressive supranuclear palsy appeared to tolerate an investigational agent that attacks tau tangles, researchers reported here at Congress of the European Academy of Neurology.

In presenting the safety and tolerability results, Nuno Mendonca, MD, medical director for neuroscience at AbbVie Deutschland GmbH & Co. of Ludwigshafen, Germany, said the company was encouraged by the results and is moving into a phase 2 study of the agent, referred to as ABBV-8E12.  

In mouse models of tauopathies, treatment with ABBV-8E12, a humanized anti-tau monoclonal antibody, reduced progression of tau pathology, reduced loss of brain volume, and improved performance on cognitive and behavioral tasks, Dr. Mendonca said in his oral presentation.

In the phase I clinical trial, researchers enrolled 30 patients at 12 sites who had been diagnosed with early Alzheimer’s disease and progressive supranuclear palsy; 23 patients received the active agent while seven received the placebo. In a series of block-ascending doses, 10 patients ended up receiving doses of 50 mg/kg.  

Dr. Mendonca said that the safety experienced at lower doses of the agent allowed for a rapid escalation of the dose to the 50 mg/kg level.

“The majority of adverse events were rated as mild or moderate in severity and were deemed unrelated to therapy,” he said. “There were no clinically concerning trends observed in the number or severity of the adverse events between the placebo and ABBV-8E12 dose groups.“

Dr. Mendonca said the researchers have performed a cerebrospinal fluid analysis of the patients in the phase 1 study, but they have not published the results yet. He added, however, that “they were encouraging enough for us to start the phase 2 studies.”

Dr. Mendonca said two phase 2 trials are underway: one in early Alzheimer's disease and one in progressive supranuclear palsy. The 96-week early Alzheimer's disease study will include 400 patients, with 100 patients receiving one of three doses of the drug and another 100 patients assigned to placebo. 

The company plans to enroll 330 patients with progressive supranuclear palsy in a second randomized phase 2 trial that will test two doses of the drug against placebo. The trial, which will include 110 patients in each arm of the trial, will assess how well patients perform on the Progressive Supranuclear Palsy Rating Scale at 52 weeks.

Commenting on the study, Patric Cras, MD, PhD, professor of neurology at the University of Antwerp in Belgium, told the Neurology Today Conference Reporter that the design of the phase 2 study on progressive supranuclear palsy had a low Mini-Mental State Examimation score of 15 as the lower level for admission, an indication of moderate cognitive impairment. “Progressive supranuclear palsy do surprising well in cognition over long periods,” he said. “A cutoff of 15 would seem to increase the heterogeneity of the trial.”

Bruno Dubois, MD, PhD, professor of neurology at the Neurological Institute of the University Salpêtrière Hospital in Paris, France, said the results of the phase 1 were interesting, but he looked forward to seeing further results.

He added that he was surprised that that the investigators focused on early Alzheimer's disease study because it is believed that tau comes into play later in the disease process. He also pointed out that the study did not appear to show memory testing as part of the endpoints of the phase 2 study.  “Tau might be more related to memory function,” he suggested.

Thursday, June 21, 2018

​BY ED SUSMAN

LISBON, Portugal—An easy-to-use three-item test based on non-contrast computed tomography (CT) findings can help neurologists predict if an intracerebral hemorrhage is likely to expand among stroke patients, researchers reported here at the Congress of the European Academy of Neurology.

To predict intracerebral hemorrhage expansion of at least 33 percent (or greater than 6 mL), Andrea Morotti, MD, a stroke attending physician at the National Neurological Institute in Mondino, Italy, and colleagues created a scoring system, the BAT Score, based on the blend sign observed on non-contrast CT, any hypodensity seen on the scans, and time from onset to performing the non-contrast CT test.

In the proposed instrument, appearance of the blend sign — the blending of the hypoattenuating and hyperattenuating regions with a well-defined margin — would add one point to the score, hypodensity would add two points to the score, and time of onset of symptoms to the CT greater than 2.5 hours would add two points to the score.

The research team developed the BAT score using data obtained from several clinical trials, comprising 1,539 patients, and a 344-person developmental cohort to validate the scores.

Dr. Morotti said zero to one on the BAT score would indicate a 7.3 percent risk of hemorrhage expansion; a score of two increases that risk to 18.9 percent; three indicates a 45.5 percent risk; four, a 51.4 percent risk; and a score of five indicates that the patient had a 75 percent risk that the hemorrhage would expand.

“This is an easy to use tool that can predict intracerebral hemorrhage expansion,” Dr. Morotti said in his oral presentation. He suggested that its use could expand the pool  of patients eligible for clinical trials, and it could provide identify patients at high risk for expansion before they are admitted to the hospital.  

He acknowledged, however, that the study was based on heterogeneous populations, and there is variability in the presence of non-contrast CT markers. He added that a consensus on these markers as well as prospective testing of the BAT score would be needed before it could become readily usable.

Commenting on the findings, Jose Ferro, MD, professor and director of neurosciences at Santa Maria Hospital at the University of Lisbon, suggested that the scoring system needs refinements. “I think you need to stratify the results by the time it takes for patients to receive a scan,” Dr. Ferro said.

“It would be more valuable for clinicians if they had two scores that could be used: one for patients who get early scans and another for patients who receive later scans. That may make a difference,” Dr. Ferro suggested.

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Thursday, June 21, 2018

​BY ED SUSMAN

LISBON, Portugal—In early trial results, the investigative agent ublituximab completely reduced brain lesions in patients with relapsing multiple sclerosis treated up to 48 weeks, researchers reported here at the Congress of the European Academy of Neurology.

The primary endpoint of the phase 2 study was to determine if treatment with ublituximab reduced levels of B cells. Ublituximab is a novel glycoengineered antiCD20 monoclonal antibody.

For the study, 48 patients were included in six different cohorts of eight patients each; the patients were about 40 years old; most were women who had been diagnosed with MS for about eight years.Twelve patients were assigned to placebo to assess safety data but switched to the active agent after one month. 

One woman dropped out of  the study due to pregnancy; another patient withdrew from the trial, reported Edward J. Fox, MD, PhD, FAAN, clinical associate professor of neurology at the University of Texas Dell Medical School in Austin.

“In all the patients and in all of the cohorts we saw a 99 percent reduction in B cells, so by week four there is an almost complete reduction of circulating CD20 cells counts,” Dr. Fox said.

Of the 14 patients who completed the 48-week study, “no gadolinium enhancing lesions were detected in any subjects,” he said. Of the 46 patients who completed the 24-week evaluation on the antiCD20 monoclonal antibody, there was also a complete absence of  T1 gadolinium-enhancing lesions compared to a mean of 3.80 lesions at baseline, a difference that was statistically significant, Dr. Fox said in his oral presentation. 

The study looked at various doses of ublituximab as well as various infusion times. Most of the patients were able to tolerate a one hour infusion treatment.

The agent was well tolerated, Dr. Fox said. Three patients reported severe fatigue and one person experienced a severe upper respiratory infection. Twenty patients reported 41 infusion reactions, all of which were determined to be mild or moderate. There were no drug-related discontinuations from the study, he said. No deaths occurred during the study, he noted. The safety results represent about 11 months of follow-up.

“The data safety monitoring board has reviewed safety labs and adverse events for all subjects, and  has not found any laboratory abnormalities or safety signals that would warrant a change in protocol,” Dr. Fox said. 

Commenting on the trial, Ralf Gold, MD, PhD, chairman of the department of neurology at Ruhr University Bochum in Germany, told the Neurology Today Conference Reporter: “These were interesting first results with this new compound ublituximab, but we really must wait for results from larger randomized studies to determine if these initial good outcomes are maintained. Once we see those results we will have to determine where this agent will fit into the treatment of people with multiple sclerosis,” Dr. Gold said.”.

Dr. Fox received funding from the study by TG Therapeutics of New York City, which developed the monoclonal antibody.

Wednesday, June 20, 2018

BY ED SUSMAN

LISBON, Portugal—About one in three patients older than 80 years old can live independently within three months of being treated with mechanical thrombectomy after a major stroke, researchers reported here at the Congress of the European Academy of Neurology.

"Not surprisingly, younger patients with similar strokes did better than the 80-year-old plus group, but we thought that a return to independent living among 32.4 percent of this group was impressive," Ary Lopes de Sousa, MD, a resident in neurology at Central Lisbon Hospital Centre, told the Neurology Today Convention Reporter.

In his oral presentation, Dr. Lopes de Sousa reviewed outcomes for patients who were living independently before they experienced an anterior circulation acute ischemic stroke that was treated by mechanical thrombectomy. The researchers defined a good pre-stroke condition as a modified Rankin Scale score of 2 or less.

He and colleagues identified 134 patients younger than 80 and compared their outcomes with patients older than 80 who were treated between November 2013 and June 2017. The older group tended to have more diagnoses of hypertension, diabetes, atrial fibrillation, and prior transient ischemic attacks.

The locale of the arterial occlusion causing the stroke was similar between the groups as was the stroke severity at admission, Dr. Lopes de Sousa said. Overall, 67.6 percent of the older patients had a poor three-month outcome — a mRS of 3 or more — compared with 46.3 percent among the younger individuals (p<0.01), he reported.

"We found no difference in the age groups for hemorrhagic transformation, for significant cerebral edema, or for death due to any cause at three months — although there was a higher percentage of death in the older patients: 23 percent in the older patients compared with 13.4 percent in the younger group (p=0.08), Dr. Lopes de Sousa said.

"For patients over 80, thrombectomy appears to be riskier than for younger patients," Dr. Lopes de Sousa said. But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it."  

"This study is important because now we have scientific data on what happens with these elderly patients," said David Vodusek, MD, PhD, emeritus professor of neurology at the University of Ljubijana in Slovenia, who was not involved with the study.

Determining if an elderly person should undergo thrombectomy remains controversial, he said, and probably will remain a controversy until a prospective study can be performed that will influence guidelines.

"Vascular neurologists have been pushing the envelope in this area and are looking at people who still look relatively healthy. They think there may be an opportunity to help them with this procedure," Dr. Vodusek said. "The study gives doctors data they can discuss with patients and their families. They can tell the family, 'He has had a big stroke. He may not recover much more, but with this treatment he may be able to function as he did previously.  And there also is a risk he could do worse or die, and then the family can make a decision."

Dr. Vodusek said that previously we just had anecdotal experiences, but with this retrospective study "we have data."

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EAN Abstract 206: Lopes de Sousa A, Mariano M, Galego S, et al. Mechanical thrombectomy for acute ischaemic [sic] stroke in the very old.