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FDA Approved Gabapentin Prodrug for Treating RLS

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FDA Approved Gabapentin Prodrug for Treating RLS 6 NEWS MAY 2011 • CLINICAL NEUROLOGY NEWS NEWS FROM THE FDA First Device Is Approved to Treat Brain Tumors Portable, battery-powered device delivers electrical surgery department at Temple University, Phila- fields to treat recurrent glioblastoma multiforme. delphia, said that while he agreed there were serious BY ELIZABETH MECHCATIE on the scalp. This creates “a low intensity, questions about the alternating electric field within the methodology used in the he Food and Drug Administra- tumor that exerts physical forces on trial, “considering the com- tion has approved a portable, bat- electrically charged cellular components, pelling nature of the clini- Ttery-powered device that delivers preventing the normal mitotic process cal problem, I could not electrical fields to the brain for treating and causing cancer cell death prior to see that with an excellent recurrent glioblastoma multiforme, division,” according to the company. safety profile, it should be despite its failure to meet a primary end Normal cells are not affected, it said. denied to the patient.” point in a pivotal phase III trial. Scattered throughout the audience at He urged Novocure “to The NovoTTF-100A system is indi- the panel meeting were about 20 people behave responsibly, to pro- cated for treating adult patients who undergoing treatment with the device, mote this device and pro- have tumor recurrence or progression which was evident from the partially mulgate it as part of a con- after receiving chemotherapy and radia- exposed electrodes under their hats and tinuum of effective tion therapy. The device is not intended the attached leads that were visible. therapies,” and not as if to be used in combination with other Several testified about their positive patients “no longer need OVOCURE cancer treatment, and it should only be experiences with TTF therapy, including N any other therapy.” used after other treatments have failed, reports of tumor shrinkage and good The concept behind TTF according to the agency. quality of life. They described their abil- “is a good idea. I like the OURTESY In March, the FDA’s Neurological ity to participate in activities such as C idea, I like the basic Devices Advisory Panel voted 7-3 with 2 coaching a child’s sports team and play- The NovoTTF-100A’s low-intensity electric field science, and I wish we had abstentions that the benefits of the de- ing with their children during treatment, kills the cancer cells before cell division. clear evidence of effective- vice exceed its risks when used as in contrast to how they felt during ness,” said Dr. Stephen monotherapy in adults who have chemotherapy, when their quality of life pany provided other analyses of the data Haines, chair and head of the neuro- exhausted surgical and radiation treat- was poor. They described the sensation that showed that TTF therapy is at least surgery department at the University of ment options for histologically or radio- of the device as negligible, with a slightly as effective as BSC, in extending overall Minnesota, Minneapolis, one of the logically confirmed recurrent glio- warm or itchy feeling at the most. survival. three panelists who voted no on the risk- blastoma multiforme (GBM). In the pivotal study, median overall But panelists agreed with FDA benefit question. The device’s manufacturer, Israel- survival, the primary end point, was 6.3 reviewers who said that some of the He said he would have preferred a based Novocure, sought an indication in months among those treated with the company’s other analyses of the data noninferiority study that “clearly that population based on the results of a device and 6.4 months among those appeared to be biased in favor of TTF, showed” the device could replace salvage company-sponsored prospective ran- treated with the best available chemo- because the per-protocol analysis chemotherapy in patients with recurrent domized trial that compared treatment therapy. excluded 23 patients who did not com- GBM. with the device to best standard of care The most common treatment-associ- plete a 4-week cycle of TTF therapy but NovoCure is conducting a phase III (BSC) chemotherapy in 237 patients with ated adverse event reported was mild to included 16 patients in the BSC arm who study of the device in patients with recurrent GBM. moderate skin irritation under the elec- received at least one dose of chemo- newly diagnosed GBM, in combination At the meeting, panelists emphasized trodes, which was easily treated, the therapy. with temozolomide. that the indication should reflect that company reported. Dr. Donald Richardson, professor and The device has been approved in the patients have also failed chemotherapy Central nervous system (43% vs. 36%) chair of the department of neurological European Union as a treatment for new- options, and that while the treatment and neuropsychiatric (10% vs. 8%) surgery at Tulane University, New ly diagnosed and recurrent GBM and for appears to be safe in the short term, the adverse events were higher among those Orleans, said that despite concerns about the treatment of non–small cell lung potential for chronic adverse effects in the TTF group than among those on the data, the device should be made cancer. should be monitored closely. BSC, but the differences were not signif- available because of its safety profile and Median survival of patients diagnosed The device weighs about 6 pounds icant. because of “clear evidence … of obvious with GBM is 15 months, and the 5-year and is intended to be worn about 20 The study was designed to show that benefit” in some patients. overall survival rate is less than 10%, hours per day. It delivers “tumor-treating TTF therapy is superior to BSC chemo- Dr. Christopher Loftus, professor of according to data cited by the company fields” (TTF) via four electrodes placed therapy, but it failed to do so. The com- neurosurgery and chair of the neuro- and the FDA. ■ FDA Approved Gabapentin Prodrug for Treating RLS BY ALICIA AULT Division of Neurology Products therapies such as dopamin- nized, “and many patients go patients with RLS. at the agency’s Center for Drug ergics, benzodiazepines, opioids, untreated as a result,” said Dr. Horizant carries a number of he Food and Drug Adminis- Evaluation and Research, in a and anticonvulsants. Atul Pande, senior vice presi- risks and contraindications. Ttration announced the statement. “Horizant provides Two other drugs were dent at GlaxoSmithKline Neuro- Even at the once-daily dose of approval of an extended-release significant help in treating these approved for the condition for sciences Medicine Development 600 mg, it can cause somno- form of gabapentin for moderate symptoms.” moderate to severe RLS: Requip Center. “GSK has been com- lence and “significant driving to severe restless legs syndrome. According to the National (ropinirole) in 2005 and Mirapex mitted to helping patients and impairment,” according to GSK The drug, known as Horizant Institute of Neurological Disor- (pramipexole) in 2006. healthcare professionals better and XenoPort. (gabapentin enacarbil), is a pro- ders and Stroke, restless legs The prevalence and incidence understand and treat this condi- It is an antiepileptic, and that drug of gabapentin. It was syndrome (RLS) is a neurologic rates of RLS are currently not tion. We are pleased to provide class of drugs has been shown to developed by XenoPort Inc. of disorder that is “characterized well known, according to the a new treatment” for moderate increase the risk of suicidal Santa Clara, Calif., and Glaxo- by unpleasant sensations in the Restless Legs Syndrome Foun- to severe primary RLS, he said in thoughts or behaviors. Horizant SmithKline. legs and an uncontrollable, and dation. There is no cure and a statement. also increases this risk, and will “People with restless legs sometimes overwhelming, urge symptoms can worsen with age. XenoPort CEO Ronald W. carry such a warning, said the syndrome can experience con- to move them for relief.” Mild to The manufacturers estimate Barrett said that Horizant was companies and the FDA. siderable distress from their moderate cases are treated with that 1%-3% of the U.S. popula- the “culmination of XenoPort’s The dosage also needs to be symptoms,” said Dr. Russell lifestyle and behavioral changes. tion is symptomatic. efforts to develop a non- adjusted for patients with renal Katz, director of the FDA’s More severe cases warrant RLS remains underrecog- dopaminergic therapy” for impairment. ■.
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