Case of PML Reported in Person Taking Tecfidera®

In December 2014, important label changes were made to the prescribing information for Tecfidera® (dimethyl fumarate, Biogen Idec) including information regarding an individual who developed PML. Most recently, Biogen has confirmed report of a second case of PML (progressive multifocal leukoencephalopathy, a viral infection of the brain that often leads to death or severe disability) that occurred in a person taking Tecfidera. According to the company, the 64-year-old patient has primary progressive MS and experienced severe and prolonged lymphopenia (decreased white blood cells) during treatment with Tecfidera. Severe and prolonged lymphopenia is a known risk factor for PML and Consideration should be given to interrupting treatment if lymphocyte counts are low for more than six months.  The patient is stable and is not hospitalized. Biogen has reported the case to the U.S. Food and Drug Administration (FDA).

PML is caused by the re-activation of a virus called the JC (John Cunningham) virus, a common virus to which many people have been exposed. PML has emerged in people using other medications, including the MS treatment Tysabri® (natalizumab, Biogen), and the MS treatment Gilenya® (fingolimod, Novartis AG).

It is not possible at this point to determine a person’s risk for developing PML because there have been so few cases in people taking Tecfidera. There have been two reported cases of PML in people with MS among the more than 155,000 individuals who have been treated with Tecfidera to date.

The symptoms of PML are diverse and can be similar to MS symptoms. For this reason, individuals should be alert to any new or worsening symptoms and report them promptly to their MS healthcare provider.  Learn more about the risk factors and symptoms of PML from the web site of The PML Consortium. Individuals who have concerns about this report should discuss it with their MS healthcare providers.

If and when the FDA or Biogen provide additional information or recommendations for people taking Tecfidera or other MS medications, the National MS Society will share it as soon as possible.

An FDA Approved Generic Form of Copaxone® (Glatiramer Acetate) For Relapsing MS Called Glatopa™ Is Launched In the U.S.

A generic equivalent of daily Copaxone® (glatiramer acetate, 20 mg), called “Glatopa”™ (Sandoz, a Novartis company, developed in collaboration with Momenta Pharmaceuticals) that was approved by the U.S. Food and Drug Administration in April, has been launched in the U.S. Glatopa is a disease-modifying therapy for people with relapsing forms of MS, including those who have experienced a first clinical episode and have MRI features consistent with MS.
The generic medication is a 20mg dose injected under the skin every day. This approval means that the manufacturer provided evidence that this generic medication is equivalent to the brand-name drug (Copaxone®).
According to Novartis which owns Sandoz, Glatopa would have a wholesale list price of about $63,000 per year. This is an estimated 15- 18 percent less than the list price of daily Copaxone. Sandoz advises that it will offer support services that include financial assistance to qualified patients, personalized injection training and 24-hour access to nurses for non-clinical questions, services not typically offered for generic medications.
“Having a generic option for one of the MS disease-modifying therapies is an important milestone, and it has the potential to increase access to MS therapies,” commented Dr. Bruce Bebo, Executive Vice President, Research at the National MS Society. “As more generic and biosimilar options become available, we are hopeful that we will start to see some price relief for people living with MS” he added.
“Health care professionals and patients can be assured that FDA-approved generic drugs have met the same rigorous standards of quality as the brand-name drug,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research, in an FDA press release. “Before approving this generic product, given its complexity, we reviewed additional information to make sure that the generic product is as safe and effective as the brand name product.” The FDA’s press release provides additional details (available here) related to how the agency determined the generic’s equivalency.
Selecting a therapy should be done by people with MS in collaboration with their MS doctors, taking into account a variety of factors, including the effectiveness of any therapy they are currently using, and weighing potential risks and benefits, costs and lifestyle factors.
About Glatopa: The FDA has approved a generic medication that has been shown to be equivalent to 20mg daily glatiramer acetate. Glatopa is not a generic version of the 40mg dose of Copaxone taken every three days. Glatiramer acetate is a synthetic protein that mimics myelin basic protein, a component of the myelin that insulates nerve fibers in the brain and spinal cord. This therapy seems to block myelin-damaging T-cells through a mechanism that is not completely understood. The approved generic form of glatiramer acetate is given by subcutaneous (under the skin) injections every day.
Potential benefits: In clinical trials of glatiramer acetate, it was shown to significantly reduce annual relapse rates and new brain lesions as shown on magnetic resonance imaging (MRI), when compared to those who were given a placebo. This therapy has had a long track record of effectiveness and safety.
As part of the generic medication approval process, the FDA requires that generics have the same active ingredients, strength, dosage and mode of administration as the brand-name medication, and that they are manufactured according to federal quality control regulations. Clinical trials are generally not required to prove equivalence to a brand-name medication.
Potential risks and side effects: Side effects of glatiramer acetate that generally resolve on their own and do not require medical attention unless they continue for several weeks or are bothersome include injection-site reactions (e.g., swelling, the development of a hardened lump, redness, tenderness, increased warmth of the skin, itching at the site of the injection); runny nose; tremor; unusual tiredness or weakness; and weight gain. There is also the potential for local damage to the skin (necrosis) and underlying tissue (lipoatrophy).
Some people using glatiramer acetate experience, at one time or another, a very temporary reaction immediately after injecting glatiramer acetate. This reaction, which often occurs only once, includes flushing or chest tightness with heart palpitations, anxiety, and difficulty breathing. During the clinical trials, these reactions occurred very rarely, usually within minutes of an injection. They lasted approximately 15 minutes and resolved without further problem.
Unusual side effects of glatiramer acetate that should be discussed as soon as possible with your doctor include hives (an itchy, blotchy swelling of the skin) or severe pain at the injection site.
The National MS Society will provide more information about generic glatiramer acetate as it becomes available.
Download prescribing information (.pdf)
Read a press release from the FDA
Read more about disease-modifying therapies and other treatments for MS and MS symptoms.

Frequently Asked Questions: Approval of Generic Glatiramer Acetate

When will generic glatiramer acetate be available for prescription?

• There is no information yet about when this medication, called Glatopa, will be available for prescription in the United States.

What will the generic glatiramer acetate cost?

• Though we don’t have specific costs of Glatopa at this time, according to Novartis which owns Sandoz, the product would have a wholesale list price of about $63,000 per year.

What does it mean for a therapy to go generic – will Copaxone still be available for prescription?

• As patent protections expire for Copaxone, other manufacturers are free to replicate it and seek drug regulatory agency approval to market it.
• For many medications available as generics, the brand-name medications remain on the market. From the information currently available, it is expected that Copaxone will continue to be available by prescription in both the 20mg once daily dose, and the 40mg dose taken every three days.

What about insurance coverage for the generic or for Copaxone – will I be forced to switch from my current medication?

• Coverage of prescriptions differs among various insurers. At this point we don’t know how insurers will handle coverage of Copaxone versus generic glatiramer acetate.

Does this generic medication 20mg dose have the same therapeutic benefit as 20 mg Copaxone?

• The FDA has a thorough review process and guidelines in place to evaluate the equivalence of proposed generic drugs to brand name drug products.
• If the FDA reviews and approves a generic medication, it means the medication’s maker has provided sufficient evidence that the generic will have the same therapeutic benefits as the brand-name product.
• The U.S. FDA is empowered by Congress to evaluate generic drug candidates through Abbreviated New Drug Applications.
• The National MS Society has confidence in the FDA’s processes.

Will patient support services be available to people who are prescribed Glatopa?

• According to Sandoz, it will offer support services that include financial assistance to qualified patients, personalized injection training, and 24-hour access to nurses for non-clinical questions.

Frequently Asked Questions: Generic Therapies for the Treatment of MS

The MS therapy landscape is continuously evolving. Two decades ago there were no disease-modifying therapies available, and now there are more than a dozen. We have also reached the point where “generic” versions of MS therapies are entering the marketplace. The following provides information about generic drugs and what they may mean for the MS community.
What is a generic medication?

• A generic medication is a product that is equivalent to a brand-name drug whose patent protections have expired.
• As part of the generic medication approval process, the FDA requires that generics have the same active ingredients, strength, dosage and mode of administration as the brand-name medication, and that they are manufactured according to federal quality control regulations.
• Generic makers are required to show that the generic drug delivers the same amount of active ingredients to the person’s bloodstream in the same amount of time as the brand-name product (referred to as “bioequivalency”).

What is the Society’s view of generic therapies for MS?

• The National MS Society advocates for increased treatment options for people with all forms of MS. Early and ongoing treatment is currently the best known way to reduce future disease activity.
• Having approved generics has the potential to increase individuals’ access to MS therapies and provides the MS community with more options.

Does the National MS Society recommend the use of this new generic MS therapy?

• The National MS Society does not make individual treatment recommendations, but as we do for all other approved therapies, we make information available to constituents so that they can make informed decisions about their treatment choices.

Do generic medications have the same therapeutic benefit as name-brand medications?

• The FDA has a thorough review process and guidelines in place to evaluate the equivalence of proposed generic drugs to brand name drug products.
• If the FDA reviews and approves a generic medication, it means the medication’s maker has provided sufficient evidence that the generic will have the same therapeutic benefits as the brand-name product.
• The U.S. FDA is empowered by Congress to evaluate generic drug candidates through Abbreviated New Drug Applications.
• The National MS Society has confidence in the FDA’s processes.

Will there be equivalent medications for all MS therapies?

• It’s possible that eventually there will be. But before any medication may be copied, the patents protecting the brand-name medication must expire. Then a maker of equivalent medications would need to apply to the FDA with a request for approval of its medication.
• The term “generic” technically applies to products that are considered drugs made through a chemical manufacturing process. Some of the MS therapies are classified as chemical drugs, and so when their patents expire, they would likely be eligible to be manufactured as generics. These FDA-approved therapies are classified as chemical drugs: Aubagio, Copaxone, Gilenya and Tecfidera.
• The other MS therapies -- Avonex, Betaseron, Extavia, Lemtrada, Plegridy, Rebif, and Tysabri -- are technically classified as “biologics.” Biologics are generally more complex and they are made from human or animal materials rather than chemical processes. The technical term for equivalent medications for biologics is “biosimilar” or “follow-on biologic.”
• The FDA has long-established requirements for the approval of generic medications, and has recently released guidelines related to the approval of biosimilars.

What is the current progress toward developing equivalent medications for MS therapies?

• The FDA just approved a generic form of glatiramer acetate, and the agency has received Abbreviated New Drug Applications for other generic forms of this medication.
• With the exception of Novantrone and Copaxone, no other disease-modifying MS medications are available in a generic form.

Where can I get more information about generic drugs and biosimilars?
The FDA’s Website has information about generic drugs and biosimilars and processes for their approval.
Copaxone is a registered trademark of Teva Pharmaceutical Industries LTD.
Glatopa is a trademark of Novartis AG

National MS Society Invests Nearly $19 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever

What do exercise, skin cells and gut bacteria have in common? They are among the new leads being explored to move us closer to a world free of MS.
The National Multiple Sclerosis Society has committed nearly $19 million to support an expected 54 new MS research projects. These are part of a comprehensive research strategy aimed at stopping MS, restoring function that has been lost, and ending the disease forever – for every single person with MS.
This financial commitment is the latest in the Society’s relentless research efforts to move us closer to a world free of MS, investing more than $50 million in 2014 alone to support 380 new and ongoing studies around the world. So that no opportunity is wasted, the Society pursues all promising paths, while focusing on three priority areas: progressive MS, nervous system repair, and wellness and lifestyle.
Just a few of the new cutting-edge research projects include a study at Stanford University using skin cells to produce repair cells for possible future use to restore nerve-insulating myelin in MS; pre-clinical studies by a commercial firm (Glialogix) to test the nervous system-protective qualities of an oral therapy repurposed to address progressive MS; a Mayo Clinic study of beneficial gut bacteria for clues to a novel therapeutic strategy for MS; and a wellness study at the University of Illinois at Urbana-Champaign testing whether an exercise program done at home can increase strength and balance and reduce falls in people with MS.
“The comprehensive nature of these new research investments is very exciting,” noted National MS Society Executive Vice President, Research Bruce Bebo, PhD.  “While we’re driving research to stop MS, restore function and end the disease forever, at the same time we’re identifying key interventions and solutions that can help people with MS live their best lives now.”  Download details about the new research awards.
Multiple sclerosis interrupts the flow of information within the brain and between the brain and the body.  Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease.  Worldwide, over 2.3 million people live with the unpredictable challenges of multiple sclerosis.
“MS research is a top National MS Society priority, with increasing annual investments to drive solutions for every person with MS,” Cynthia Zagieboylo, President and CEO of the Society. “We fund the entire research spectrum, propelling novel ideas into the lab, translating breakthroughs into clinical trials, and moving success in clinical trials into new treatments for people living with MS.”
To find the best research with the most promise, the National MS Society relies on more than 130 world-class scientists who volunteer their time to carefully evaluate hundreds of proposals every year.  This rigorous evaluation process assures that Society funds fuel research that delivers results in the shortest time possible.
There are FDA-approved therapies that can impact the underlying disease course in people with the more common forms of MS.  However, none of these can stop progression or reverse the damage to restore function.  National MS Society-funded research paved the way for existing therapies – none of which existed 20 years ago – and continues to be a driving force of MS research.

FDA Accepts Resubmitted Lemtrada™ Application for Review*

Genzyme, a Sanofi company, announced today that the United States Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for Lemtrada™ (alemtuzumab), a proposed treatment for relapsing forms of multiple sclerosis (MS). This application was recently submitted after the FDA did not approve Lemtrada in late December 2013, when Genzyme stated that they had received a Complete Response Letter from the FDA. This letter informed them that the application for their drug was “not ready for approval.” A new decision is expected in the last quarter of 2014.

The reason that the drug did not receive approval, according to the FDA, lies in the design of the Phase III studies. These compared the effectiveness and adverse effects of Lemtrada against an approved treatment for MS, versus a placebo (with no active ingredients). Because of dramatically different side effects between the two different medications, these studies were “unblinded,” meaning that both the patients and treating doctors were aware of which drug each of the patients was receiving. Whenever possible, clinical trials are double-blinded to prevent any potential bias toward the treatment being evaluated.

In order to resubmit the application, Genzyme and the FDA had “constructive discussions” to determine what would be necessary for the medication to be reconsidered for approval. In the resubmitted application, Genzyme provided additional data to address the specific issues that are of concern to the FDA. These data are from the same studies that were included in the original application.

Lemtrada is a humanized monoclonal antibody given in annual courses by intravenous (IV) infusion. It works by depleting the circulating lymphocytes (B and T cells). Lymphocytes are immune-system cells produced to fight infection and disease, and with MS, these cells are misdirected to cause damage to the nerves of the central nervous system (CNS) and the nerves’ protective covering (myelin). Lemtrada was originally approved by the FDA in 2001 for the treatment of a certain type of leukemia (B-cell chronic lymphocytic leukemia), using “Campath” as the trade name.
Lemtrada is already approved in 33 countries for the treatment of MS, including 28 countries in the European Union. Additional marketing applications for this MS medication are under review by other regulatory agencies around the world.

*Note:________________________________________________
Lemtrada™ (alemtuzumab, formerly Campath) did not receive approval from the United States Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS) in December, 2013 because of the design of the Phase III studies.

MS Trial Alert: Researchers in California, Colorado, New Mexico and Pennsylvania Recruiting Women with Progressive or Relapsing MS for Study of Estriol to Improve Cognition

Summary: Investigators in California, Colorado, New Mexico and Pennsylvania are recruiting 64 women with MS relapsing-remitting, secondary-progressive, or primary-progressive for a 12-month study in which the sex hormone estriol will be compared with inactive placebo for effects on cognitive function. Participants can remain on their prescribed MS medication throughout the study. Rhonda Voskuhl, MD (University of California at Los Angeles) is the principal investigator of the trial. The study is funded by various private donors to the UCLA program.

Rationale: Estriol levels rise to very high levels naturally during late pregnancy, a time when most women’s MS disease activity declines. This led some to suspect that estriol may be responsible for this easing of symptoms during pregnancy. Dr. Rhonda Voskuhl (University of California, Los Angeles) and others showed that in mice estriol treatment was indeed protective. They then explored this lead with Society support, showing that estriol decreased disease activity in a small, early-phase trial of estriol in 12 women with MS. The National MS Society funded a team of investigators at 15 medical centers to conduct a two-year, controlled clinical trial of estriol added to standard therapy to treat MS. This trial recently reported results.

Meanwhile, Dr. Voskuhl’s team also has shown that, in mice, treatment with estrogen (a hormone related to estriol) can improve nerve impulse transmission in an area of the brain related to learning and memory, called the hippocampus. Problems with learning, memory and other cognitive functions are common in MS. (Laboratory Investigation 2012;92:1234) These and other observations led to the launch of this clinical trial to test the ability of estriol to improve cognition in women with MS.

Eligibility and Details: The researchers are seeking volunteers who are women 18 to 50 who have been diagnosed with relapsing-remitting, secondary-progressive, or primary-progressive MS. If participants are on standard MS treatments, they may remain on these medications during the study.  Participants should not have had a relapse within 30 days before the day of trial enrollment. A cognitive test called the Paced Auditory Serial Addition Test (PASAT) will be administered to determine whether the participant qualifies for the study. Participants are excluded if they are on oral contraceptives, hormone replacement therapy, progesterone IUDs or other sex hormones during screening and during the 12-month study period. For more details about enrollment criteria, please contact the site nearest you (listed below).

Participants are being randomly assigned to receive oral estrogen (8mg/day) or inactive placebo for one year. The primary outcome is improvement in cognitive function as measured by PASAT scores. Secondary outcomes under study include measurements from brain MRIs, cognition, quality of life, depression, and fatigue.

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact (for information about all sites nationwide):

University of California, Los Angeles
Contact: Jenny Bardens
Phone: (310) 206-2176
Email: jbardens@mednet.ucla.edu

New Treatment of MS

 The United States Food and Drug Administration (FDA) has approved Gilenya (fingolimod) as a first-line treatment for relapsing forms of multiple sclerosis (MS). Gilenya is the first oral disease-modifying therapy available for the long-term treatment of MS. The approval of a treatment that may be taken orally (by mouth), versus injection or infusion, is exciting news for members of the MS community