The first oral therapy for MS could come to market by autumn, following the June vote (21-3) of an FDA advisory panel supporting that the drug be approved for first-line therapy in MS. Novartis' fingolimod (FTY720) is expected to be marketed under the name Gilenia.
The advisory panel unanimously agreed that at 5mg, current dosing of the drug “appears to have an acceptable safety profile,” but voted 20-5 that Novartis should be required to conduct studies of the drug at lower doses (0.25mg) after it reaches market. FDA is expected to make a final decision on approval by September.
Novartis reports that data reviewed by the committee provided evidence that FTY720 offered superior efficacy of over interferon beta-1a IM and to placebo, in reducing relapses and brain lesions. Data from a two year placebo-controlled study showed FTY720 significantly delayed disability progression. In trials, adverse events included transient, dose-related, generally asymptomatic heart rate reduction and infrequent transient AV conduction block at treatment initiation, mild (1-3mm Hg) blood pressure increase, macular edema (more common with 1.25mg than the 0.5mg target dose), and generally asymptomatic, reversible elevation of liver enzymes, Novartis says.
In a related development, Genzyme Corporation has reported that the four-year follow-up data from its completed Phase II multiple sclerosis trial showed “an estimated 71 percent of alemtuzumab treated patients remain free of clinically-active disease as much as three years after most patients received their last course of the investigational compound.”
Genzyme announced in June that alemtuzumab received FDA fast-track status for the treatment of patients with relapsing remitting multiple sclerosis (RRMS).
The CAMMS223 Phase II trial measured alemtuzumab against interferon beta-1a in early, active, relapsing-remitting multiple sclerosis patients who had received no prior therapy. In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while interferon beta-1a was given to patients three times per week, every week for three years. Results showed:
An estimated 71 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking interferon beta-1a (p<0.001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without progression of disability as measured by the Expanded Disability Status Scale (EDSS) throughout the course of the study;
Approximately 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 68 percent of patients taking interferon beta-1a; and
About 77 percent of alemtuzumab-treated patients were relapse-free compared to 49 percent of patients taking interferon beta-1a.
Alemtuzumab is currently marketed in the US under the brand name Campath/MabCampath and is indicated for the treatment of B-cell chronic lymphocytic leukemia.
A new, office-based imaging device for tracking and measuring axonal change was introduced at this year's AAN meeting in Toronto. The Spectralis Tracking Laser Tomographer from Heidelberg measures these changes within the retinal nerve fiber layer by capturing high resolution cross-sectional images of the eye.
The development was initiated by several studies showing that patients with multiple sclerosis have a thinner RNFL than healthy patients, a truism for patients with and without prior episodes of optic neuritis. RNFL thickness has also been shown to correlate with symptoms measured in physical disability scores such as the Expanded Disability Status Scale (EDSS).
The device uses light to create 2D and 3D images of the back of the eye. Heidelberg Engineering, the device manufacturer, says the technology has 100 times the resolution of MRI and utilizes a unique combination of two imaging methods: optical coherence tomography and confocal scanning laser ophthalmoscopy.
“This combination drives the company's proprietary TruTrack Active Eye Tracking technology which not only provides high-resolution, detailed images of the layers of the eye, but also enables precise measurements for tracking subtle change over time,” according to a release by the company.
First-of-its-Kind Treatment for PBA Progressing
The FDA has acknowledged receipt of Avanir Pharmaceuticals' Complete Response to the October 2006 Approvable Letter for Zenvia (dextromethorphan/ quinidine) in the treatment of pseudobulbar affect (PBA). It will be considered a Class 2 response, and FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of October 30, 2010.
Zenvia is a combination of two compounds: the therapeutically active ingredient dextromethorphan and the enzyme inhibitor quinidine, which serves to increase the bioavailability of dextromethorphan. “This first-in-class drug candidate is believed to help regulate excitatory neurotransmission in two ways: through pre-synaptic inhibition of glutamate release via sigma-1 receptor agonist activity and through postsynaptic glutamate response modulation via uncompetitive, low-affinity NMDA antagonist activity,” according to a news release from the company.
Brain Injuries and Sleep
People who experience brain injuries may produce lower amounts of melatonin, thus affecting their sleep, according to a new report in the May 25 issue of Neurology. The study followed 23 people who had severe traumatic brain injury an average of 14 months prior and 23 healthy people of the same age spent two nights in a sleep laboratory. “The people with brain injuries had other differences in their sleep patterns, [such as spending] less of their time in bed actually asleep than the healthy participants did, or a 'sleep efficiency' percentage of 82 compared to 90 for the healthy group,” according to a release from the AAN. They were awake more after originally falling asleep, or an average of 62 minutes per night compared to 27 minutes for the group that did not suffer brain injury.
In addition, the study goes on to report that people with brain injuries spent more time in non-REM sleep. “Those with brain injuries spent an average of 24 percent of their time in slow-wake sleep, compared to 20 percent of the time for healthy participants,” according to the release.
Racial Disparity in Epilepsy Care
The results of an alarming study published in the May issue of Archives of Neurology found racial disparities in the surgical management of intractable temporal lobe epilepsy (TLE). Researchers sought to determine whether race and/or predictive factors for patients with TLE who receive ATL (anterior temporal lobe) resection exist on a national level. They examined data from 1988 through 2003.
The analysis reported that of the 5,779 adults admitted with TLE, 562 (9.7 percent) received ATL. Multivariate analyses revealed that African American race (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.38-0.84; P = .005) and increased age (OR, 0.98; 95% CI, 0.97-0.99; P < .001 per 1-year increase in age) independently predicted decreased likelihood of receiving ATL for TLE, while private insurance increased the odds of ATL receipt (OR, 1.85; 95% CI, 1.39-2.46; P < .001). They report that these findings remained stable over time.
Cambia Now on the Market
Cambia (Diclofenac potassium for oral solution, Nautilus Neurosciences) is now available for acute treatment of migraine with or without aura, following FDA approval in June 2009. The novel, watersoluble, buffered powder is the only prescription NSAID approved for acute migraine treatment, Nautilus says. It is quickly absorbed and achieves peak plasma concentrations. In clinical trials reported by Nautilus, Cambia was shown to reduce pain intensity more significantly than placebo, as early as 15 minutes following treatment.
New Botulinum Toxin Offers Positive Data
A novel botulinum neurotoxin type A free from complexing proteins (NT 201, Xeomin, Merz) was the focus of several studies presented at this year's annual meeting of the AAN.
In two placebo-controlled studies in patients with focal dystonia (blepharospasm or cervical dystonia), treatment with NT 201 was significantly superior to placebo (P01.268). Mean percentage improvement over placebo (approx. 23 percent) in the primary efficacy criteria (showing local muscle relaxation) was similar across studies. Patient-evaluated global response to NT 201 was significantly superior to placebo (p<0.001), with 53.4 percent of patients treated with NT 201 reporting at least moderate symptomatic improvement compared with 12 percent of controls. Data were available from 613 patients receiving NT 201.
To assess the safety and efficacy of repeated NT 201 injections in patients with cervical dystonia, 217 patients who completed a 20-week placebocontrolled, double-blind study of NT 201 in 37 US centers could enter an extension phase and were treated with NT 201 (120 U or 240 U; five injection intervals) over one year (48 weeks + 20-week follow-up) (P01.270). Injection intervals were at least six weeks, with a mandatory visit four weeks after each injection. The mean duration before reinjection was 10.0 (2.4) to 14.5 (5.9) weeks. TWSTRS-Total score was significantly improved at four weeks after each injection as well as at the study termination visit versus the first injection visit of the extension phase. During the extension period, 77.1 percent (118/153) of patients experienced one adverse event. Dysphagia, neck pain, and sinusitis were the most frequently reported AEs. No serious AEs were considered to be related to BoNT/A. The overall incidence of AEs reduced with each injection interval, indicating no cumulative effect with repeated doses.
Finally, investigators analysed the presence of neutralizing antibodies resulting from subjcts' previous treatment with botulinum toxin preparations containing complexing proteins (P01.271). A total of 696 patients with focal dystonia were screened for the presence of neutralizing antibodies, and 98 (14.0 percent) had a positive result in the FIA antibody test. Following further screening, 46 of these patients (6.6 percent of the total population) tested positive for neutralizing antibodies in the HDA.
AED Therapy Helps Contain Epilepsy Costs
The expense of emergency room visits, hospitalizations, and costs not associated with anti-epilepsy drugs (AEDs) seem to account for the high costs of epilepsy care, according to a new study. Presented at the International Society of Pharmacoeconomic Outcomes Research (ISPOR) annual meeting in May, the data show that annual AED-related costs remain stable regardless of disease severity, but the cost of non-drug treatment of epilepsy increases disproportionately with disease severity.
The two-year observational study was based on an analysis of insurance records for 9,163 USbased patients with epilepsy who had filed at least two claims for AEDs. Total costs of AED treatment ranged from $6,000 to $33,000 per year, depending on disease severity. Severity of epilepsy was based on number of ER visits; three or more visits signified “most severe” epilepsy.
The analysis did uncover a 10-fold increase in “other” costs—such as those for ER visits, hospitalizations, lab and radiology tests, and physician visits— from “least severe” epilepsy to “most severe.” The difference between AED and “other” costs increased significantly with epilepsy severity, as well as with increased comorbidities and age. However, the cost difference decreased with better AED compliance.
The study, sponsored by UCB, Inc. was titled, “Health Care Costs Stratified by Epilepsy Severity in a US Commercially Insured Setting.”