November 15, 2010
The first drug specifically developed to treat uncontrollable laughing or crying, also called pseudobulbar affect, or PBA, has been approved by the U.S. Food and Drug Administration. Nuedexta™ (dextromethorphan hydrobromide and quinidine sulfate, formerly called AVP-923, Avanir Pharmaceuticals) is an oral therapy shown in clinical trials to significantly reduce episodes in people with MS, ALS and other disorders.
Comment: “This FDA approval represents a significant step forward for people who live with the debilitating effects of pseudobulbar affect,” said Dr. Nicholas LaRocca, Vice President of Healthcare Delivery and Policy Research at the National MS Society. “For people who experience unexplained bouts of inappropriate laughing or crying, this new therapy has the potential to substantially help both them and their families.”
Background: It is currently estimated that approximately 10% of persons with MS experience episodes of uncontrollable laughing and/or crying that are unpredictable and seem to have little or no relationship to actual events or the individual’s actual feelings. This condition, which also affects people with other neurological conditions, is thought to result from lesions – damaged areas – in emotional pathways in the brain. It is important for family members and caregivers to know this, and realize that people who experience these episodes may not always be able to control their expression of emotions. Until now, no medication was approved specifically to treat this condition.
Avanir Pharmaceuticals has been conducting trials of Nuedexta in its current and earlier formulations for several years as a treatment for pseudobulbar affect in a number of disorders, including MS and ALS. Nuedexta is a patented, orally-administered combination of dextromethorphan and an enzyme inhibitor known as quinidine. Quinidine slows down the breakdown of dextromethorphan in the body, which results in a sustained elevation of dextromethorphan in the brain.
In 2006, Avanir received a letter from the FDA indicating that the drug was “approvable” and requesting that additional studies be conducted, leading to the phase III study that was recently published. (Annals of Neurology, published online September 13, 2010). Results of that study suggested that the drug significantly reduced the rate of episodes of pseudobulbar affect by about 47-49 percent compared to placebo. Secondary outcomes, including patient diaries and episode-free days, also suggested significant benefit among groups taking Nuedexta.
Safety: According to the approved prescribing information, Nuedexta may cause serious side effects including changes in heart rhythm, and is not recommended (contraindicated) for people who have certain types of heart conditions unless they have an implanted pacemaker. The most common adverse reactions in patients taking Nuedexta capsules are diarrhea, dizziness, cough, vomiting, weakness, swelling of feet and ankles, urinary tract infection, flu, elevated liver enzymes, and flatulence. Since Nuedexta may cause dizziness, precautions to reduce the risk of falls should be taken, particularly for those with motor impairment affecting gait or a history of falls.
Drug Interactions: Nuedexta can interact with other medications causing significant changes in blood levels of those medications and/or Nuedexta. Nuedexta is contraindicated in patients receiving drugs that both prolong QT interval (part of heart function) and are metabolized by CYP2D6 (e.g., thioridazine and pimozide) and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine. Nuedexta is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs – a class of antidepressant drugs such as Marplan, Nardil or Parnate) or in patients who have taken MAOIs within the preceding 14 days.
September 22, 2010
The FDA in the United States has announced today the approval of Gilenya® for the treatment of relapsing remitting MS. Gilenya®, also known as fingolimod, is a pill taken daily.
Positive results from two large-scale phase III clinical trials of oral fingolimod (FTY720) have been published showing it significantly reduced multiple sclerosis relapse rates, and one of the trials also suggested it could slow the progression of disability. Medical Memo Update January 27, 2010
For more information about Gilenya® please see Frequently Asked Questions.
August 31, 2010
Health Canada has approved Sativex® for the treatment of spasticity in MS.
Health Canada has approved Sativex® [delta-9-tetrahydrocannabinol 27 mg/mL (from Tetrabinex® - cannabis sativa L. extract - Bayer Inc.) as adjunctive treatment for symptomatic relief of spasticity in adult patients with multiple sclerosis. In 2005 Sativex® was approved for as adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis. Canada is now the third major country to approve Sativex® for symptomatic relief of spasticity in adult patients with MS.
June 28, 2010
FDA Agrees to Fast Track Status for Drug Being Tested for MS
It was announced by the drug maker Genzyme Corporation (Cambridge, MA) that intravenous alemtuzumab has been designated by the U.S. Food and Drug Administration as a "Fast Track Product." This designation should expedite its future review by the FDA after the sponsor submits results of current phase 3 trials that are underway (these studies have completed enrollment but are not yet completed).
Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the FDA as a single agent for treatment of patients with B-cell chronic lymphocytic leukemia. Its ability to target immune cells led to its testing as a possible treatment for relapsing-remitting MS.
Earlier Phase 2 studies showed that treatment with alemtuzumab reduced the accumulation of disability and the frequency of relapses in people with early relapsing-remitting MS, compared to Rebif® (interferon-beta-1a-rebif/index.aspx, interferon beta-1a, EMD Serono, Inc. and Pfizer, Inc.). (New England Journal of Medicine 2008 359;17:30-45)
June 14, 2010
FDA Panel Recommends Approval of Oral Fingolimod for Relapsing MS -- If agency follows advice, it would become first oral disease-modifying therapy for MS
June 1, 2010
ExtaviaT is now available in Canada.
A second betainterferon-1b is now available for management of Multiple Sclerosis.
In Nov of 2009, Health Canada approved Extavia ™ for treatment of Multiple Sclerosis and as of May, it is available for prescribing in Canada. Extavia is a betainterferon-1b, and is identical to Betaseron™. For prescribing information, please see the product monograph.
Extavia’s™ patient support program, Extracare, can be accessed at extavia.ca, using the DIN 02337819. In addition to product support, it offers telephone consultation with psychology and dietetic services for patients on Extavia™.
May 10, 2010
New FDA warning for Tysabri
The U.S. Food and Drug Administration has issued a safety announcement that the risk of progressive multifocal leukoencephalopathy (PML) increases with the number of infusions received of Tysabri (natalizumab) (www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor
As of January 21, 2010, there have been 31 confirmed cases of PML worldwide since natalizumab was re-introduced in 2006 in concert with a risk minimization plan (Tysabri Outreach Unified Commitment to Health Care, or TOUCH). Eight deaths have occurred. In all cases, natalizumab was used as monotherapy.
The FDA has determined that the PML risk increases with the number of infusions received. The overall rate of PML is 0.5 cases per 1000 patients. The cumulative rate of PML in patients who have received >12 infusions is 0.8 per 1000; with >24 infusions the rate is 1.3 cases per 1000. An insufficient number of patients have received the drug for >36 months to determine the PML risk.
The PML risk with continued use of natalizumab will be added to the drug label. The revised label will also include information on the risk of Immune Reconstitution Inflammatory Syndrome (IRIS); this rare condition is characterized by a severe inflammatory response that can result in a severe decline in patient functioning as immune function is restored (www.fda.gov/Safety/MedWatch/
The number of IRIS cases following natalizumab discontinuation is unknown. To date, three cases have been reported in the literature (Langer-Gould et al. N Engl J Med 2005; 353: 375-381; Wenning et al. N Engl J Med 2009; 361: 1075-1080; Linda et al. N Engl J Med 2009; 361: 1081-1087).
Despite these risks, the FDA believes that the clinical benefits of natalizumab outweigh the risks of the drug and Tysabri will remain available in the U.S. for MS patients with an inadequate response or poor tolerability to alternative MS therapies.
©Neurosens, April 28, 2010. Used with permission.
For the French version:
©Neurosens, April 28, 2010. Used with permission.
Translated from the original version by the MS Society of Canada.
March 19, 2010
FDA Approves Botox® for Treating Spasticity, or Tightness, in Upper Limbs
A new use for Botox® (onabotulinumtoxin A, Allergan, Inc.) was approved by the U.S. Food and Drug Administration, providing an additional treatment option for people with MS or other disorders who may experience spasticity in muscles of the elbow, wrist and fingers. Spasticity is an often painful muscle tightness that can make movements difficult. In clinical trials largely involving people with spasticity after stroke, targeted injections of Botox into muscles were found to be beneficial and safe.
Botox is a powerful neurotoxin that temporarily blocks connections between the nerves and muscles, resulting in short-term relaxation of the targeted muscle. Injections have been shown in clinical trials to relieve spasticity in individual muscles for up to three months. For many years some doctors have injected Botox directly into overactive muscles in people with MS-related spasticity who did not get relief from the first-line oral medications such as baclofen and tizanidine. While the oral medications continue to be the most effective strategy to manage generalized spasticity of the upper and lower limbs, having Botox specifically approved for treating upper limb spasticity adds a welcome strategy. Botox is also being tested in MS for its usefulness in the management of certain types of urinary symptoms.
FDA Approval: Botox is a well-studied drug that is now approved for five different indications in the U.S. According to a company press release, the FDA approval for treating upper spasticity was based on results of three double-blind, placebo-controlled studies, two of which were published, involving people who had upper-limb spasticity after stroke. (Arch Phys Med Rehabil. 2004 Jul;85(7):1063-9; N Engl J Med. 2002 Aug 8;347(6):395-400). The studies showed benefit over placebo in treating upper limb spasticity.
According to the approved label, the dosing regimen should be tailored to the individual based on the size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, the patient’s response to previous treatment, or adverse event history. Generally it can be given every 12 weeks.
The most common adverse events included pain in the arms, fatigue, muscle weakness, nausea and bronchitis. According to the label, it is not known whether Botox is safe or effective in treating spasticity in children younger than 18. The medication carries a boxed warning that Botox injections may cause serious side effects that can be life threatening. These include problems swallowing, speaking or breathing, and the possibility that the toxin may spread to other areas of the body away from the injection site.
If you have questions about the use of Botox for the treatment of spasticity, please consult your healthcare provider.
March 3, 2010
Gilenia – the Oral Drug for Relapsing MS Formerly Known as FTY720 – Receives Priority Review from FDA – Could take as little as six months for an approval decision
Novartis International AG has been granted a priority review for its oral therapy formerly known as FTY720 or fingolimod, now called Gilenia®, the U.S. Food and Drug Administration, according to a press release from the sponsor dated February 22, 2010. Novartis applied to the FDA and European regulators for marketing approval of this compound for the treatment of relapsing MS in December 2009, using supporting data from two phase 3 trials. There are currently no approved oral disease-modifying therapies for MS.
According to the FDA, a “priority review” designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. A priority review means that the time it takes FDA to review a new drug application is reduced. The goal for completing a priority review is six months from the application date, but the press release suggests that this period could be extended if the FDA requires additional time to evaluate any risk management program that might be proposed for Gilenia.
February 15, 2010
The Common drug review has given a negative review for Copaxone’s CIS indication. The CDR review committee expanded its recommendation to include : “In light of the Committee’s reasons for recommendation, drug plans that currently list therapies for clinically isolated syndrome may wish to review their listing criteria.” To read the full recommendation please see:
January 26, 2010
The U.S. Food and Drug Administration has approved the marketing of Ampyra™ (dalfampridine, formerly known as fampridine SR, from Acorda Therapeutics) for its ability to improve walking speed in people with any type of multiple sclerosis.
Ampyra, formerly known as fampridine SR, is a tablet containing a sustained-release formula of 4-aminopyridine, which blocks tiny pores, or potassium channels, on the surface of nerve fibers. This blocking ability may improve the conduction of nerve signals in nerve fibers whose insulating myelin coating has been damaged by MS.
For more information about the fampridine please see: