With 100,000 Canadians living with Multiple Sclerosis (MS), and three people newly diagnosed every day, Canada has one of the highest prevalence rates for the disease in the world. Most people are diagnosed with relapsing MS in their twenties and thirties, and MS is the most common neurological disease affecting young adults in Canada.
Genzyme, a Sanofi company, announced November 20th that the Canadian province of Ontario Public Drug Benefit Program has included AUBAGIO (teriflunomide) 14 mg on the provincial drug formulary as a first-line oral agent for people in the Canadian province living with relapsing remitting multiple sclerosis (RRMS) under its exceptional access program (EAP) for frequently requested drugs. For more information on the updated EAP reimbursement criteria, visit: http://bit.ly/1qIhNN3
Genzyme’s AUBAGIO (teriflunomide) 14 mg was approved by Health Canada In November 2013 as monotherapy for treatment of patients with RRMS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. The approval was based on efficacy data from two Phase III clinical trials TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis). In the TEMSO trial, AUBAGIO 14 mg significantly reduced the annualized relapse rate (p=0.0005) and the time to disability progression (p=0.0279) at two years versus placebo in patients with RRMS. In the TOWER trial, AUBAGIO 14 mg significantly reduced the annualized relapse rate (p=0.0001) and the time to disability progression sustained for 12 weeks (p=0.0442) was statistically significantly reduced versus placebo in patients with RRMS (see more on these trials below).
“Finally, Ontario patients will have access to what is proving to be the simplest, safest and most consistently effective oral medication for the treatment of relapsing MS,” says Dr. Mark S. Freedman, a Professor of Neurology at the University of Ottawa.
According to Genzyme, AUBAGIO is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for AUBAGIO is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system (CNS). AUBAGIO is supported by one of the largest clinical programs of any MS therapy, with more than 5,000 trial participants in 36 countries. Some patients in extension trials have been treated for up to 10 years.
Described by the National Multiple Sclerosis Society, Aubagio isa pyrimidine synthesis inhibitor, is an 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) — which in turn reduces the proliferation of T and B immune cells that are active in MS and also inhibits the production of immune messenger chemicals by T cells.
Aubagio was approved by the U.S. Food and Drug Administration (FDA) in September, 2012 for patients with relapsing forms of multiple sclerosis. In one phase III study involving 1088 people with relapsing MS (796 completed the trial), oral Aubagio reduced relapses compared with placebo over at least 108 weeks. Of two different doses tested during the TEMSO trial (7 mg and 14 mg), the higher dose also slowed progression of disability. Both doses also had a favorable effect on several MRI measures, including a smaller increase in total lesion volume and fewer new and actives lesions compared with placebo.
Two subsequent phase III trials have been published and the FDA approved inclusion of these trial results in the prescribing information for Aubagio in 2014. New information includes the ability of Aubagio to reduce the risk of relapse in people who have experienced a first clinical event suggestive of MS (clinically isolated syndrome).
• In the TOPIC Study, 618 people with clinically isolated syndrome (CIS — a first clinical episode suggestive of MS) were randomly assigned to receive 7 mg of Aubagio, 14 mg of Aubagio, or placebo once daily for 108 weeks. The primary outcome measure was time to relapse. A secondary outcome measure was time to relapse or the occurrence of new tissue damage on MRI scans, whichever occurred first. Compared to placebo, the risk of relapse was reduced by 42.6% among those taking the 14 mg dose, and by 37.2% among those taking the 7 mg dose. For the secondary endpoint, the risk of relapse or occurrence of new tissue damage was reduced by 34.9% in the 14-mg group and 31.4 % in the 7-mg group compared with the placebo group.
• In the TOWER Study, 1,169 people with relapsing forms of MS were randomly assigned to receive 7 mg or 14 mg of Aubagio, or placebo, once daily for 48 weeks. The primary endpoint was whether Aubagio reduced the average number of relapses per year significantly more than placebo. Secondary endpoints included the time to disability progression confirmed for at least 12 weeks. Aubagio 14 mg reduced relapses by 36.3.% versus placebo and Aubagio 7 mg reduced relapses by 22.3% versus placebo. In the 14 mg group, the risk of sustained disability progression was reduced by 31.5%, while the lower dose did not significantly reduce progression.
Regarding safety and counter-indications, Genzyme cautions that for persons who have severe liver problems. AUBAGIO may cause serious complications that can be life-threatening, and risk may be higher if you take other medicines that affect your liver. Your healthcare provider should do blood tests to check your liver within 6 months before you start AUBAGIO and monthly for 6 months after starting AUBAGIO.
For persons who are pregnant or are of childbearing potential and not using effective birth control. AUBAGIO may harm an unborn baby. Patients should have a pregnancy test before starting AUBAGIO. After stopping AUBAGIO, continue to use effective birth control until you have made sure your blood levels of AUBAGIO, which can linger for up to two years, are lowered. If you are a man whose partner plans to become pregnant, you should stop taking AUBAGIO and talk with your healthcare provider about reducing the levels of AUBAGIO in your blood. If your partner does not plan to become pregnant, use effective birth control while taking AUBAGIO.
Dr. Paul O’Connor, Director, MS Clinic and MS Research at St. Michael’s Hospital, says: “I am pleased that AUBAGIO has gained an Ontario listing as it provides another reasonably safe and effective treatment choice for our MS patients.”
“We are pleased that the Ontario Ministry of Health and Long-Term Care remains responsive with their coverage of new treatments for those living with multiple sclerosis in our province,” said Sylvia Leonard, President, Ontario and Nunavut Division and Vice President, National Client Services. “This responsiveness means Ontarians living with MS have greater access and more choice when it comes to first-line treatments including oral therapies to manage the effects of their disease. For individuals with MS who are interested in exploring treatment options, we encourage them to consult with their health care team to find the course that is most appropriate for them.”
“We congratulate the Government of Ontario for making AUBAGIO once-a-day available to people in the province suffering with multiple sclerosis. In doing so, Ontario becomes the third province in Canada to grant access to this novel therapy,” says Peter Brenders, General Manager, Genzyme Canada. “We applaud the Government of Ontario for recognizing the value brought by this important new treatment, not only as an oral alternative to injectables, but as a first-line agent for newly diagnosed patients.”
As part of its commitment to those living with MS, Genzyme has developed the MS One to One program which offers comprehensive information services and ongoing education, as well as reimbursement navigation. Staffed by dedicated MS nurses and highly trained representatives, MS One to One provides support for individuals living with MS, their healthcare providers, family and loved ones.
For more information, visit:
The National Multiple Sclerosis Society
St Michael’s Hospital
Ottawa Hospital Research Unit