Aubagio® (Oral Teriflunomide) Receives Approval
Written by Susan Wells Courtney
On September 12, 2012, Sanofi and its subsidiary Genzyme announced that the United States Food and Drug Administration (FDA) had approved their new drug, Aubagio® (oral teriflunomide), for relapsing forms of multiple sclerosis (MS). The FDA had accepted their New Drug Application (NDA) in October 2011. This is the ninth disease-modifying therapy approved by the FDA for the long-term treatment of MS. Of these nine, Aubagio is the second approved medication for MS that is taken orally.
This drug is an immunomodulator that affects the production of T and B cells. It inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. It also may inhibit nerve degeneration by reducing the production of free radicals, possibly decreasing the risk of infections and other complications linked to chemotherapy-like drugs.
Aubagio has been approved in two dose levels: 7 mg and 14 mg. The medication is produced in film-coated tablets and is taken once daily, with or without food. Since the higher dose shows greater effectiveness, this dose may be more frequently prescribed. However, for individuals who may be more sensitive to the drug and experience greater side effects, the 7-mg dose may be more appropriate. The drug is expected to be available beginning October 1.
The TEMSO trial for relapsing-remitting MS (RRMS) compared 7-mg and 14-mg doses of Aubagio in 1,088 individuals. Both doses significantly reduced the annualized relapse rate by approximately 31 percent. The 7-mg dose resulted in a 39.4-percent reduction in brain-lesion volume on MRI compared with placebo, while the 14-mg dose resulted in a 67.4-percent reduction. The 14-mg dose also reduced the risk of sustained disability progression by 29.8 percent relative to placebo. The number of gadolinium-enhancing lesions was reduced with both doses compared with placebo, and there was a trend toward a greater effect with the higher dose.
The TOWER efficacy study is also testing 7-mg and 14-mg doses versus placebo. This study of 1,110 individuals with RRMS is scheduled to be completed in February 2013. Its primary endpoint is the annualized relapse rate, with a secondary endpoint of time to disability progression. Top-line results of this trial were announced in June, 2012. In the study, patients receiving the higher dose of 14 mg had a 36.3-percent reduction in annualized relapse rate and a 31.5-percent reduction in the risk of 12-week sustained accumulation of disability, compared to placebo. Patients treated with lower 7-mg dose of Aubagio experienced a 22.3-percent reduction in annualized relapse rate, compared to placebo.
Common adverse events include headache, elevations in liver enzymes, hair thinning, diarrhea, nausea, neutropenia (a condition that reduces the number of certain white blood cells that normally fight infection), and paresthesia (tingling, burning, or numbing sensation). More severe adverse events include the risk of severe liver injury and the risk of birth defects if used during pregnancy. A "black box" warning appears on the labeling of Aubagio, which lists these two risks.
Because of these warnings, physicians must take certain precautions to minimize any risks. With regard to liver injury, blood tests for liver function must be performed within six months prior to starting Aubagio, and then every month for the first six months. With regard to pregnancy, Aubagio may only be prescribed to women of childbearing years if they are using reliable birth control. If liver damage is detected, or if someone becomes pregnant while taking this drug, accelerated elimination of the drug is prescribed. This removes more than 98 percent of the drug within 11 days.
For More Information
For more information about Aubagio, members of the MS community may visit www.aubagio.com. Individuals may also contact Genzyme's "MS One to One" program, which provides access to nurses experienced with MS patients on Genzyme treatments. This service may be accessed by calling (855) MSOne2One - or (855) 676-6326, Monday through Friday from 8:30 am to 8:00 pm. Information and support is also available at www.MSOnetoOne.com. Financial assistance will be available to individuals who qualify.
Members of the MS community may also call MSAA's Helpline at (800) 532-7667 for additional information and assistance.
DMF and Lemtrada™ Submitted for FDA ApprovalDimethyl Fumarate (DMF)
In February 2012, Biogen Idec announced that it had submitted an NDA to the FDA for the approval of Dimethyl Fumarate (DMF, formerly known as BG- 12) for the treatment of relapsing-remitting multiple sclerosis (RRMS). A decision is expected from the FDA in the very near future.
DMF is an oral medication taken daily. It may have a distinct dual mechanism of action - as an immunomodulator with anti-inflammatory properties, as well as a neuroprotective agent, due to its activation of a substance that is critical for resistance to cellular damage. DMF is initially being studied in relapsing-remitting MS (RRMS).
In the Phase III DEFINE study, DMF was given either two-times (BID) or three-times (TID) daily, compared to placebo. The annualized relapse rate (ARR) at two years was reduced by 53 percent (BID group) and 48 percent (TID group), while the risk of disability progression was reduced by 38 percent (BID group) and 34 percent (TID group). In the Phase III CONFIRM study, which used the same treatment regimens (plus a separate group given Copaxone® [glatiramer acetate]), DMF reduced the ARR by 44 percent (BID group) and 51 percent (TID group), compared to placebo at two years. In both studies, DMF significantly reduced MS brain lesions.
A continuation study is ongoing, as well as a combination-therapy study. Trials to date indicate that DMF is safe and that its overall tolerability improves with continued use. Side effects include skin flushing and gastrointestinal symptoms.
In June 2012, Genzyme (a Sanofi company) announced that they had submitted Lemtrada™ (alemtuzumab) for approval with the FDA for the treatment of relapsing forms of multiple sclerosis. Genzyme is developing Lemtrada for MS in collaboration with Bayer HealthCare. This drug has previously been referred to as Campath.
In August 2012, Genzyme received a Refuse to File letter from the FDA. This was in response to its submission for the approval of Lemtrada as a treatment for relapsing MS. Following discussions with the FDA, the agency requested that Genzyme modify how the data was presented, so that the FDA could more easily navigate the application. No additional data or further studies are necessary and the company plans to resubmit its application in the near future.
Lemtrada is administered in one-course yearly by intravenous infusion over threeto- five consecutive days. The drug is a humanized monoclonal antibody that targets a protein present on the surface of mature lymphocytes and is approved for the treatment of B-cell leukemia. This drug was granted Fast Track status by the FDA in June 2010.
In the CAMMS223 Phase II study of 334 individuals with early, active RRMS, the relapse rate in patients on Lemtrada was about one attack in nine years. This is the lowest relapse rate ever reported for an MS drug. More than 50 percent of the Lemtrada-treated patients actually improved. An extension study showed that at a five-year assessment, 87 percent were free of sustained disability accumulation, 72 percent were relapse-free, and 65 percent were free of clinical disease activity.
Side effects include a reduction in blood clotting, thyroid disorders, infusion reactions, and infection. Patients need to be monitored closely due to risk of significant toxicities.
|Last Updated on Wednesday, 03 October 2012 14:27|