Epilepsy Update: Reports from the AES
New Device for Epilepsy
A new investigational device that utilizes responsive brain neurostimulation (RNS) significantly reduced the frequency of seizures among patients with medically intractable partial onset epilepsy enrolled at 31 sites located in the US, according to new information presented at the American Epilepsy Society's (AES) 63rd Annual Meeting. The RNS System, “demonstrated a statistically significant reduction in seizure frequency in the treatment group as compared to the sham stimulation group,” according to manufacturer NeuroPace.
During the last two months of the three-month blinded evaluation period, patients in the treatment group had a mean percentage reduction of 29 percent in their disabling seizures compared to 14 percent reduction for controls. Over the long-term, open label period of the trial, NeuroPace says, “at least 12 weeks of data were available for 171 study participants; 47 percent of these subjects experienced a 50 percent or greater reduction in their seizure frequency...as compared to their baseline.”
The system is intended to identify a patient's unique “signature,” indicating the start of a seizure. The system then continuously monitors brain electrical activity and delivers brief, mild electrical stimulations when a seizure seems imminent. This differs from DBS, which provides continuous stimulation. The company announced plans to submit a premarket approval application to the FDA in early 2010 seeking approval for the treatment of epilepsy.
Strengthening the Case for Lacosamide.
New research presented at the AES meeting, “demonstrate sustained efficacy in adult patients taking Vimpat for up to three years, and a consistent long-term tolerability profile,” as reported by UCB. Lacosamide was associated with sustained efficacy as measured by percent change in seizure frequency and responder rates among patients on active treatment for six, 12, 18, 24, 30, or 36 months. No new types of treatment-emergent adverse events occurred with long-term use in an analysis of patients taking Vimpat for a median of two years. Rates of TEAEs were similar to those in the pivotal clinical trials.
A preliminary retrospective analysis of Vimpat phase II/III studies reported that rates of “spontaneously reported adverse events potentially related to cognition among Vimpat patients were dose-dependent and not significantly different from those observed in patients taking placebo.”
FDA Actions: Ability Labeling Partly Inadequate
An FDA panel has ruled that the current label for antipsychotic drug aripiprazole (Abilify) does not properly warn of excessive weight gain risk in children. The 12-0 vote said the current label was inadequate and FDA staff were to revise the labeling, which could include “moving all information onmetaboliceffectsofdruginchildrentothewarningsection,” according to Reuters.
Seniors have often celebrated the benefits of drinking prune juice to promote a healthy lifestyle, but according to a new study, they may not want to overlook the benefits of blueberry juice. Published online (Jan. 4) in the Journal of Agricultural and Food Chemistry, a study suggests that older subjects who drank blueberry juice had improved memory over those who didn't. The study involved a sample of nine older adults with early memory changes. Improved paired associate learning (p = 0.009) and word list recall (p = 0.04) were observed at 12 weeks. Further, there were trends suggesting reduced depressive symptoms and lower glucose levels. The authors conclude that their findings, “suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.”
OSA Drug Completes Positive Phase II Trial
Vivus announced positive results from a Phase II study evaluating the safety and efficacy of Qnexa, an investigational drug for the treatment of obstructive sleep apnea. According to the report, the drug demonstrated statistically significant improvement in the apnea/hypopnea index in patients with OSA treated with Qnexa for 28 weeks. Patients treated with Qnexa also experienced significant weight loss, improvements in blood pressure, and overnight blood oxygen levels. The phase II study (OB-204) was a single-center, randomized, double-blind, placebo-controlled parallel group trial including 45 obese men and women (BMI 30 to 40) 30 to 65 years of age. Patients enrolled were diagnosed with OSA based on an AHI greater than or equal to 15 (moderate to severe) at baseline. In addition to receiving treatment or placebo, all patients were provided with an intensive lifestyle modification program.
New Data on Stroke
Stroke has declined from the second to the third leading organ- and disease-specific cause of death in the US, according to report published online in the journal Stroke (Jan. 14). Researchers assessed for the most recent 10-year period (1996 to 2005) and found that age-adjusted stroke death rates declined by 25.4 percent; lung cancer (which declined by 9.2 percent) surpassed stroke as the second leading cause of death in 2003. Heart disease, despite nearly a 32 percent decline, remains the leading cause of death. Stroke now places fifth in cause of death in men and fourth in cause of death in whites but remains the second leading cause of death in women and blacks.
New Guidelines on Adolescent Cerebral Palsy
Botulinum toxin type A is an effective treatment for spasticity in children and adolescents with cerebral palsy, but also poses some risk, according to new guidelines from the American Academy of Neurology and the Child Neurology Society. FDA is investigating isolated cases of generalized weakness following use of botulinum toxin type A for the indication. The guideline (Neurology, Jan. 26) recommends the drug diazepam be considered for short-term treatment of spasticity, although generalized side effects may occur. Tizanidine may also be considered, but neurologists must consider the risk of liver toxicity.
FDA Expanding CT Scrutiny
The FDA is working with state and local health authorities after having identified additional patients who were exposed to excess radiation during CT perfusion scans. The FDA issued an initial safety notification in October after learning of 206 patients who had been exposed to excess radiation at Cedars-Sinai Medical Center in Los Angeles over an 18-month period. At least 50 additional patients have been identified who were exposed to radiation up to eight-times the expected level during their CT perfusion scans. These cases so far involve more than one scanner manufacturer. FDA recommendations now suggest that:
1. Facilities assess whether patients who underwent CT perfusion scans received excess radiation.
2. Facilities review their radiation dosing protocols for all CT perfusion studies to ensure that the correct dosing is planned for each study.
3. Facilities implement quality control procedures to ensure that dosing protocols are followed every time and the planned amount of radiation is administered.
4. Radiologic technologists check the CT scanner display panel before performing a study to make sure the amount of radiation to be delivered is at the appropriate level for the individual patient.
5. If more than one study is performed on a patient during one imaging session, practitioners should adjust the dose of radiation so it is appropriate for each study.
Dementia Drug Enters More TestingAnother clinical trial is under way for davunetide. The drug, made by Allon Therapeutics, has previously demonstrated human efficacy in Phase II trials in patients with amnestic mild cognitive impairment and in patients with cognitive impairment associated with schizophrenia. The company hopes the trials will present more dosing flexibility by evaluating the drug in patients with frontotemporal dementias.