Written by Susan Wells Courtney
Reviewed by Jack Burks, MD
Phase III Results Announced for Oral Laquinimod
On March 15, 2012, Teva Pharmaceutical Industries Ltd. and Active Biotech announced that the results of the ALLEGRO Phase III study of oral laquinimod were published in the March 15, 2012 edition of the New England Journal of Medicine. The article, titled “Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis,” (G Comi, et al.; N Engl J Med. 2012;366:1000-9), details this randomized, double-blind Phase III study conducted at 139 sites in 24 countries. Of the 1,106 participants with relapsing-remitting MS (RRMS), half received oral laquinimod (0.6 mg once daily), and the other half received a placebo, over a period of two years.
The study showed that oral laquinimod slowed the progression of disability (as measured by Expanded Disability Status Scale [EDSS]) by 36 percent, and reduced the annual relapse rate by 23 percent for individuals with RRMS. Additionally, oral laquinimod reduced the number of new or enlarging lesions (as shown on magnetic resonance imaging [MRI]), and also reduced the progression of brain atrophy (braintissue loss) by 33 percent. The most common adverse events were headaches, nasopharyngitis (inflammation of the nasal passages and upper part of the throat), and back pain. Elevated liver enzymes occurred more often in the treatment group, although these were transient, without symptoms, and reversible. No deaths were reported in the treated group.
Application Submitted for BG-12; FDA Approves Avonex® Pen™ and Initial Dosing Regimen
On February 28, 2012, Biogen Idec announced that they have submitted an application to the United States Food and Drug Administration (FDA) for approval of BG-12 (dimethyl fumarate), an experimental oral drug for the treatment of relapsingremitting multiple sclerosis (RRMS). In clinical trials, including the Phase III DEFINE study (with 1,200 patients) and the Phase III CONFIRM study (with 1,232 patients), BG-12 reduced MS-disease activity significantly, while showing favorable safety and tolerability data. These placebo-controlled trials were conducted globally, studying the effects of 240 mg of BG-12 given (orally) either twice or three times per day over the course of two years.
Also on February 28, 2012 Biogen Idec announced that the United States Food and Drug Administration (FDA) had approved both a new device (the Avonex Pen) as well as a new initial-dosing regimen for Avonex (interferon beta-1a). These two approvals are aimed at assisting patients who are either taking Avonex presently, or who are just starting Avonex.
Many of these news items also appear on MSAA’s website (www.mymsaa.org) under “Recent News.” Some of the online versions of these news items may include some additional information. For more information on any of the approved or experimental treatments for MS, please refer to the “MS Research Update” appearing in the Summer/Fall 2011 issue of The Motivator. You may view, download, and print this article from our website by going to “Publications” and then selecting “The Motivator” in the left navigation. Readers may also contact MSAA’s Helpline at (800) 532-7667 for more information.
The Avonex Pen
The Avonex Pen is the first intramuscular autoinjector approved for an MS medication. The other self-injected treatments for MS are given via subcutaneous injections, which do not require as deep of an injection. Since Avonex is injected intramuscularly, patients may find this type of self-injection to be more difficult, and they may experience increased pain and anxiety as well. The Avonex Pen is designed to be easier to use (than the present Avonex Prefilled Syringe alone) and is designed to reduce both pain and anxiety.
The Avonex Pen incorporates the current Avonex Prefilled Syringe, along with a thinner and shorter needle. Other features of the Avonex Pen include an automated insertion of the needle and delivery of the medication, as well as a design that helps to stabilize the device while performing an injection.
Initial Dosing Regimen
The FDA has also approved a schedule for starting low and gradually increasing the dose of Avonex at the start of therapy. The reason for this change in the initial dosing of Avonex, which introduces the drug gradually (known as titration), is to help reduce the incidence and severity of flu-like symptoms. These can often occur when starting an interferon therapy.
The new dosing regimen is provided on the Avonex label to physicians and patients, and may be facilitated using the Avostartgrip kit. This kit includes a set of three devices that work with the Avonex Prefilled Syringes, each filled with the titrated doses of Avonex. Specifically, 7.5 mcg is given in the first week, 15 mcg is given for week two, and 22.5 mcg is administered for week three. The full dose (of 30 mcg) starts in week four. PLEASE NOTE: This titration schedule should only be used by individuals who are just starting Avonex.
For More Information
For more information, please see Biogen Idec’s press releases on these topics at www.biogenidec.com. For general information about Avonex, please visit www.avonex.com.
Antibody Test Identifies New Risk Factor for PML
On January 20, 2012, the United States Food and Drug Administration (FDA) announced that three factors are now identified with increasing the risk of progressive multifocal leukoencephalopathy (PML) for individuals with multiple sclerosis (MS) being treated with Tysabri® (natalizumab). PML is a potentially fatal brain infection with the JC virus (JCV), in people with weakened immune systems. The FDA has approved a labeling change, which adds the results of a newly approved test for the presence of anti-JCV antibodies, to the two previously listed risk factors. The following three PML risk factors now appear on Tysabri’s labeling:
- The presence of anti-JCV antibodies, which identifies a previous exposure to the JC virus
- Longer duration of Tysabri treatment, especially after two years
- Prior treatment with an immunosuppressant medication, such as mitoxantrone (Novantrone®), azathioprine (Imuran®), methotrexate, cyclophosphamide (Cytoxan®), or mycophenolate
Each of these three factors increases the PML risk and the combination of all three increases the risk to as high as 11 in 1,000 (or slightly more than one percent). The new validated JCV antibody detection test (Stratify JCV Antibody ELISA test) was cleared by the FDA on January 20, 2012 and is now commercially available from Quest Diagnostics. A positive test indicates a previous JCV exposure, but does not indicate the development of PML.
JCV typically remains dormant in those exposed to the virus, but may become active when the immune system is weakened. An individual needs to be anti-JCV antibody positive in order to be at risk of developing PML, although a person who is negative could be exposed to the virus at any time. Whether or not a person has received any prior treatment for their MS, about 55 percent of individuals with MS are anti-JCV positive.
For more information on this label change, please see Biogen Idec’s press release at www.biogenidec.com and the FDA announcement at www.fda.gov/Drugs/DrugSafety/ucm284240.htm.
FDA Safety Announcement for Gilenya
On December 20, 2011, the FDA posted a Safety Announcement on its website, noting the death of an individual withMS on the day following a first dose of Gilenya (in November, 2011). The article states: “At this time, FDA cannot conclude whether the drug resulted in the patient’s death. FDA is continuing to evaluate the case and will communicate any new information that results from this investigation.” It also advises: “Patients with MS should not stop taking Gilenya without talking to their healthcare professional.”
To view the FDA announcement, please go to www.fda.gov/Drugs/DrugSafety/ucm284240.htm. Anyone with questions may also contact Novartis at (888) NOWNOVA (888-669-6682) or call MSAA’s Helpline at (800) 532-7667.
European Agency Recommends Increased Monitoring with First Dose of Gilenya
On January 20, 2012, the European Medicines Agency (EMA) announced that it has started a review of Gilenya (fingolimod) in response to reports of potential heart issues associated with the first dose of this drug. The EMA is responsible for the scientific evaluation of medicines developed for use in Europe, similar to the Food and Drug Administration (FDA) in the United States. According to a press release issued by the EMA, “The review was started following reports of heart problems in patients taking Gilenya, as well as the death of one patient in the United States less than 24 hours after the first dose. The exact cause of this patient’s death is still unexplained.”
The EMA is advising doctors in the European Union to “intensify cardiovascular monitoring” following the initial dose of Gilenya. Readers should note that (1) this advisory does not apply to doctors in the United States and (2) no changes will be made to Gilenya’s labeling at this time.
To view EMA’s press release, visit www.ema.europa.eu, select “News and Events,” followed by “News and Press Release Archive,” and then type “Gilenya” in the keyword search and enter. Scroll below the search box to select, “European Medicines Agency starts review of Gilenya (fingolimod).”