FDA Approves Oral Teriflunomide – Brand Name Aubagio® – as Disease-Modifying Therapy for Relapsing M - National Multiple Sclerosis Society

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FDA Approves Oral Teriflunomide – Brand Name Aubagio® – as Disease-Modifying Therapy for Relapsing MS

September 12, 2012

FAQs Updated 4/3/13

The U.S. Food and Drug Administration has approved teriflunomide once-daily pills (Aubagio,® Genzyme, a Sanofi company) to treat relapsing forms of MS. This is the second oral disease-modifying therapy approved for the treatment of multiple sclerosis. The company has also applied for regulatory approval in other parts of the world.

“We are greatly encouraged to see a new oral therapeutic option become available to people living with MS,” advised Bruce A. Cohen, MD, Professor, Davee Department of Neurology and Clinical Neurosciences at Northwestern University’s Feinberg School of Medicine, and incoming Chair of the National MS Society’s National Medical Advisory Committee. “As with any new therapy, the long-term safety of Aubagio will need to be carefully monitored,” he added. Dr. Timothy Coetzee, Chief Research Officer at the National MS Society agreed. “With the collaborative research underway around the world today, this is an extremely hopeful time for anyone who is diagnosed with MS.”

Read the FDA’s press release.

About Teriflunomide/Aubagio: Multiple sclerosis involves immune system attacks on the brain and spinal cord. Aubagio (pronounced oh-BAH-gee-oh) is a novel oral compound that inhibits the function of specific immune cells that have been implicated in MS. It is related to leflunomide, a drug used to treat rheumatoid arthritis. Aubagio can inhibit a key enzyme required by white blood cells (lymphocytes), reducing the proliferation of T and B immune cells active in MS and also inhibiting the production of immune messenger chemicals by T cells. It is not thought to affect resting immune cells that are not in an activated state. Two doses (7mg and 14 mg) have been approved.

Potential benefits: Three large clinical trials of Aubagio have been completed, and at least two more are ongoing. In the phase III TEMSO study, Aubagio reduced the average number of MS relapses and disease activity on MRI scans significantly more than inactive placebo in 796 people with relapsing forms of MS.

In a recently completed phase III TOWER study involving 1,169 people with relapsing-remitting MS, oral Aubagio reduced relapses compared with placebo over at least 48 weeks, according to a company press release. Of two different doses tested during the TOWER trial (7 mg and 14 mg), the higher dose also slowed progression of disability. Read more about this study.

In another study, called TENERE, Aubagio was compared with Rebif® (interferon beta-1a, EMD Serono and Pfizer) in relapsing MS, and did not reach its primary endpoint (the main question posed by the study) -- the “risk of failure,” meaning the first occurrence of a relapse, or permanent discontinuation of the study treatment, whichever came first. There was no significant difference in the numbers of participants who experienced events defined as treatment failure among the Aubagio and Rebif groups.

Potential risks and screenings: In trials to date, Aubagio was generally safe and well tolerated. The most common side effects experienced by participants in clinical trials include diarrhea, abnormal liver tests, nausea, flu, and hair thinning.

The prescribing information includes a boxed warning related to the potential for liver damage in persons taking Aubagio. There is also a warning that Aubagio is not indicated for women who are pregnant or women with childbearing potential who are not using reliable contraception. The prescribing information also contains information on how to clear Aubagio from the system in case that is required.

Before people begin taking Aubagio, they should have a blood test, of have had one within six months, to detect levels of liver enzymes and levels of blood cells (Complete Blood Count). They should also have their blood pressure checked, and have a screening test for tuberculosis (tuberculin skin test). It should be verified in women of childbearing potential that they are not pregnant before taking Aubagio.

After starting Aubagio, blood tests to detect liver enzymes should be done at least monthly for the first six months, and then patients should be monitored for signs of liver damage. Patients should also be monitored for signs of infection, and blood pressure should be checked periodically.

Taking a disease-modifying therapy is currently the best way to reduce MS disease activity and future deterioration. Selecting an MS 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.

Physicians and people with MS can contact Genzyme for information about Aubagio and patient support programs by calling: 1-855-676-6326, or visit the company’s Website: www.MSOnetoOne.com.

Download the Prescribing Information and Medication Guide (.pdf)

Read more about disease-modifying therapies and other treatments for MS and MS symptoms

Read about National MS Society efforts to speed research in progressive MS

FAQ About FDA’s Approval of Oral Teriflunomide – Brand name Aubagio – for Relapsing MS


Updated 4/3/13

Q. What is Aubagio?
A. Aubagio is a small molecule that inhibits the function of specific immune cells that have been implicated in MS. It is related to leflunomide, a drug used to treat rheumatoid arthritis.  Aubagio can inhibit a key enzyme required by white blood cells (lymphocytes), reducing the proliferation of T and B immune cells active in MS and also inhibiting the production of immune messenger chemicals by T cells. It is not thought to affect resting immune cells that are not in an activated state. 

Q. What types of MS is Aubagio approved to treat?
A. The FDA has approved Aubagio for the treatment of patients with relapsing forms of MS . In other words, people who experience periodic MS attacks, such as those who have relapsing-remitting MS or secondary-progressive MS with relapses.

Q. How is Aubagio taken?
A. The pill is taken orally once per day.

Q. When will Aubagio be available by prescription?
A. Aubagio is expected to be available by prescription by October 1, 2012.

Q. How effective is Aubagio?
A. Results from three phase III studies have been released. For the TOWER trial, 1,169 people with relapsing MS were randomly assigned to receive Aubagio 7 mg or 14 mg, once daily by mouth, or inactive placebo, for 48 weeks. According to a company press release, Aubagio 14 mg (the dose approved by the FDA) reduced relapses by 36.3% versus placebo. In the 14 mg-group, the time to disability progression was reduced by 31.5%.

In the TEMSO trial, 1088 people with relapsing MS were randomly assigned to receive 7 mg or 14 mg of Aubagio, or inactive placebo for 108 weeks; 796 (73.2%) completed the study. After two years, both doses of Aubagio significantly reduced the average number of relapses in a year by as much as 31.5% over placebo. Fewer of those on the higher dose (14mg) experienced progression of disability compared with those on placebo (20.2% progressed on therapy vs. 27.3% on placebo). On imaging scans, the total volume of tissue damage and active areas of damage were reduced significantly more in both Aubagio groups than in the placebo group.

For the TENERE trial, 324 people with relapsing MS were randomly assigned to receive Aubagio 7 mg or 14 mg, or Rebif® (interferon beta-1a, EMD Serono Inc. and Pfizer) 44 mcg three times per week subcutaneously for 48 weeks. The primary endpoint was “risk of failure,” meaning the first occurrence of a relapse, or permanent discontinuation of the study treatment, whichever came first. There was no significant difference in the numbers of participants who experienced events that constituted the definition of treatment failure among the Aubagio and Rebif groups, according to a company press release. Relapse rates did not differ significantly either.

Q. What are the potential side effects of Aubagio?
A. Aubagio may cause diarrhea, nausea, hair thinning, back pain, abnormal liver tests,  flu, and lowered levels of white blood cells, which can increase the potential for infections. It can also increase blood pressure. The prescribing information includes a boxed warning related to the potential for liver damage in persons taking Aubagio. There is also a warning that Aubagio is not indicated for women who are pregnant or women with childbearing potential who are not using reliable contraception. The prescribing information also contains information on how to clear Aubagio from the system in case that is required. The Prescribing Information and Medication Guide (.pdf) provides full information on potential side effects, and signs that may indicate a problem.

Q. What if I am taking Aubagio and I plan to become pregnant?
A. A woman taking Aubagio who plans to become pregnant should stop taking the drug, continue using effective birth control, and undergo one of the treatment regimens designed to remove the drug from their systems quickly. Your doctor should ensure that blood levels of Aubagio are low enough before you stop using birth control.

Q. What if I am taking Aubagio and I accidentally become pregnant?
A. If you become pregnant while taking Aubagio (or within two years of stopping Aubagio), stop taking Aubagio and talk to your doctor right away. You should undergo one of the treatment regimens designed to rapidly remove the drug from your system, and consult with an obstetrician regarding potential harm to the fetus.

Q. What if I am a man taking Aubagio and there is a chance my partner could become pregnant?
A. Men should stop taking Aubagio if they plan to father a child, and they should contact their healthcare provider to undergo one of the treatment regimens designed to remove the drug from their systems quickly. If a man’s female partner does not plan to become pregnant, both of you should use effective birth control while you are taking Aubagio. Aubagio remains in your blood as long as two years after you stop taking it, so continue to use effective birth control until Aubagio blood levels have been checked and are low enough.

Q. Should I switch from my current therapy to Aubagio?
A. The decision about whether to take Aubagio should be made in collaboration with your MS doctor, taking into account a variety of factors including the effectiveness of any therapy you are currently using, the potential risks and benefits, as well as costs and lifestyle factors. Important questions to be considered and discussed with your doctor in terms of Aubagio include:
  • How am I doing on my current therapy?
  • What is my tolerance for the risk of known side effects?
  • What is my tolerance for the risk of adverse consequences that might emerge with longer-term use?
  • How will my medication choice affect my ability or plans to become pregnant?
  • What are the comparative costs of my current therapy versus Aubagio?

Q. How does the effectiveness of Aubagio compare to other available therapies?
A. Clinical trial results to date suggest that Aubagio has effectiveness against MS relapses in a similar range as the first generation disease-modifying therapies (interferons and glatiramer acetate). Aubagio has not been compared to all other available therapies, but in a comparison trial against Rebif, there were not significant differences in the outcomes tested.

Q. How long would a person take Aubagio?
A.  There is no specified time limit for taking Aubagio.

Q. Will a person taking Aubagio have to get any special medical tests or monitoring?
A. Before people begin taking Aubagio, they should have a blood test, of have had one within six months, to detect levels of liver enzymes and levels of blood cells (Complete Blood Count). They should also have their blood pressure checked, and have a screening test for tuberculosis (tuberculin skin test). It should be verified in women of childbearing potential that they are not pregnant before taking Aubagio.

After starting Aubagio, blood tests to detect liver enzymes should be done at least monthly for the first six months, and then patients should be monitored for signs of liver damage. Patients should also be monitored for signs of infection, and blood pressure should be checked periodically.

Q. What are some symptoms of liver problems?
A. People taking Aubagio should call their healthcare provider immediately if they have any of these symptoms of liver problems: nausea, vomiting, stomach pain, loss of appetite, tiredness, yellow tinge to the skin or whites of the eyes, or dark urine.

Q. What are some symptoms of infection?
A. People taking Aubagio should tell their healthcare provider if they have any of these symptoms of infection: fever, unusual tiredness, body aches, chills, nausea, vomiting.

Q. What will Aubagio cost?
A. The actual cost to an individual who has MS will depend on the provisions of his or her insurance coverage and the degree to which that individual will be eligible for programs designed to assist with out-of-pocket costs.

Q. Will my health insurance cover Aubagio?
A. Coverage will depend on individual insurance plans.

Q. Where can I get information about the support that Genzyme will provide to help patients?
A. For more information about support services provided by Genzyme, people can call the company’s MS One To One line at: 1-855-676-6326, or visit the company’s website: www.MSOnetoOne.com.

Q. Did the National MS Society support the research and development of Audagio?
A. No. Although the Society was not involved in the development of this treatment, the application of this drug to MS was made possible by the Society’s substantial investments in discovery research projects that helped define the immune pathways involved in MS disease activity.

Q. Are there other oral disease-modifying therapies available or in development for MS?
A. Yes, there are other oral therapies available now or in development. Gilenya is an oral therapy approved for relapsing MS forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Others are in development. Oral BG12 (sponsored by Biogen Idec), for relapsing MS, is currently being reviewed by the FDA for marketing approval. Another oral therapy in later stages of development for relapsing MS is laquinimod (sponsored by Teva Pharmaceutical Industries). Read more about ongoing clinical trials in MS

Q. I’ve been hearing news about other new treatments in development for MS. What are some details?
A.  Oral and infrequent-dose disease-modifying therapies are just two of many exciting research avenues that address ways to stop MS progression, restore function and end MS forever. Just a few new approaches being explored include potential benefits of the hormone estriol, adult stem cell transplantation, large-scale clinical trials for progressive MS, trials of agents aimed at protecting the nervous system, and studies of vitamin D and CCSVI (chronic cerebrospinal venous insufficiency). In addition, the newly formed International Collaborative on Progressive MS is a global effort to speed research and treatments on progressive MS.

Q. Is Aubagio being tested in progressive MS?
A. Not at this time.

Q. Why aren’t there more treatments for progressive MS?
A. Virtually every therapy approved for relapsing MS has been tested, or is now in testing, in people with progressive forms of the disease, including primary-progressive MS and secondary-progressive MS. Up to now, clinical trials involving people with relapsing MS often rely on counting relapses or doing MRI scans to detect immune activity. The fact that there is no easy way to detect progression quickly is one reason why drug development for progressive MS is behind. Right now there are large clinical trials going on in progressive MS, including tests of Tysabri,® Gilenya,® Ocrelizumab, and Masitinib.

Aubagio is a registered trademark of Genzyme, a Sanofi company
Gilenya is a registered trademark of Novartis
Rebif is a registered trademark of EMD Serono and Pfizer.
Tysabri is a registered trademark of Biogen Idec and Elan Pharmaceuticals.

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. 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. MS affects more than 2.3 million people worldwide.

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