April 25, 2013 -- With the arrival of Tecfidera this spring, people with multiple sclerosis now have three oral drugs to choose from to treat the relapsing form of the disease.
Tecfidera (dimethyl fumarate) joins two other oral MS drugs. Aubagio (teriflunomide) was approved in 2012, and Gilenya (fingolimod) was approved in 2010.
For the 350,000 people in the U.S. who have MS, these drugs represent a treatment breakthrough. Other MS drugs used to treat the relapsing form are injected or given through an IV.
All three oral MS drugs are expensive. Tecfidera's wholesale cost is nearly $55,000 a year. Gilenya and Aubagio cost $60,000 and $45,000 a year. The actual cost to a patient will depend on what type of insurance coverage they have.
With these three oral drugs, what do patients need to know about benefits and side effects?
For answers, WebMD turned to Barbara Giesser, MD, professor of neurology and clinical director of the University of California Los Angeles Multiple Sclerosis Program. She was not involved in the clinical trials for any of the three drugs.
How does Tecfidera work?
Giesser: It appears to have anti-inflammatory actions and brain-protective actions. The main problem in MS is that immune cells are getting into the brain and the spinal cord and they are attacking the nerves. One of the main ways they cause damage is by inflammation, particularly in relapsing-remitting MS.
So Tecfidera does a number of different things to lower inflammation and lower the ability of the immune cells to get in and attack the central nervous system. Additionally, it may protect nerves from damage.
How do Gilenya and Aubagio work?
Giesser: Gilenya prevents the T-cells, the immune cells, from getting out of the lymph nodes. I tell my patients it's like the "roach motel" model of immunity. They can check in, but they can't check out.
Gilenya also may protect the brain.
Aubagio basically decreases production of T-cells and B-cells, which are also immune system cells.
Has there been a head-to-head comparison of the three oral MS drugs?
Giesser: No, as far as I know they have not been compared to each other.
The thing is, if you are going to tell a patient about a new drug, the first thing they are going to ask you is, 'Is it better than the old drug?' And what you have to say is these drugs have not been compared against every single one of our older drugs.
You can't compare across [different] trials because there are different patient populations, different conditions, and so on.
If you look at the three newer drugs, Gilenya vs. placebo reduces relapses by around 54%. Aubagio vs. placebo reduces relapse by around 30%. Tecfidera reduces relapses in the neighborhood of 50%.
It suggests that some of the newer drugs are more effective than our older drugs, but only relatively, because there hasn't been a head-to-head comparison.
What are the major side effects for each of these drugs?
Giesser: Gilenya has known side effects of liver enzyme elevations [potentially causing liver disease], lowering of the white blood cell count [reducing infection-fighting ability], and slowing the heart rate.
A year or so after it came out, there were sudden deaths. These were people who had pre-existing heart problems or were on heart medication. So they had to change the labeling. Now, if someone has certain types of heart conditions or is on certain types of heart medication, Gilenya is not prescribed.
For Aubagio, you have to watch out for white blood cell counts, liver function, infections, and hair loss. I'm told the hair loss is fairly mild. The main issue with Aubagio is it's known to cause birth defects and affects the sperm as well. The effects can persist after you stop taking it for up to two years. People have to be absolutely very meticulous about practicing contraception while on Aubagio.
I'm told most of the flushing and the digestive effects only happen over the first month or two. After that, it decreases. If you take it with food, that is supposed to diminish the side effects.
The potential advantage that Tecfidera has over the other two drugs is that its active ingredient has been used in Germany for almost 20 years to treat psoriasis. But as with any drug, we have to see what happens when it's out in the real world [for treating MS].
Editor's note: An active ingredient similar to the one in Tecfidera has been linked to four cases of a rare but sometimes fatal brain disease, progressive multifocal leukoencephalopathy (PML). That side effect has not been seen in patients taking Tecfidera, the manufacturer says. The four patients diagnosed with PML had additional risk factors. They include taking drugs that suppress your immune system or having prolonged periods of low white blood cell counts. In August 2013, the FDA said it was investigating a man in Europe who developed PML while taking Gilenya.
Why are these medicines only approved for relapsing MS and not for progressive MS?
Giesser: Most people who have MS have this relapsing-remitting form.
We don't have a good handle yet on all of the mechanisms that produce damage in progressive MS. It is much less understood.
Some of these newer medicines appear to have properties that may make them effective for progressive MS. In fact, they are being tested.
Why might my doctor decide to keep me on the medicine I'm taking and not switch me to the new medicines?
Giesser: If your doctor thinks your current medication is working, meaning that you are not having relapses and/or not having changes on your MRI, then he or she may say, 'Your medicine seems to be working.' If it ain't broke, don't fix it type thing.
Some doctors are pretty conservative. They may want to wait a little bit to see how the [new] medicines behave.