Clarifying and Enabling

First Oral MS drug.

Let me clarify.

The headline on many websites is: AMPYRA (Fampridine SR) IS FIRST SYMPTOM MANAGEMENT DRUG DEVELOPED SPECIFICALLY TO TREAT MS, THE FIRST ORAL MS THERAPY APPROVED FOR MS, AND THE FIRST NEW FDA APPROVED THERAPY TO COME THROUGH THE MS PIPELINE SINCE 2004

Seem simple enough?

Now, lets delve into the language: "first" vs. "symptom" vs. "management" vs "specifically to treat MS" vs. "first oral MS therapy" vs. "first new FDA approved therapy to come through MS pipeline since 2004."

So, we can understand that Ampyra (dalfampridine) is:

1. Oral

2. MS drug

3. First

This is obviously exciting, but is it an MS disease modifying drug or MS symptomatic treatment (just like we use Lioresal/Baclofen for muscle tightness/spasticity, Provigil/Modafinil for MS-related fatigue etc.)?

Seem confusing enough?

Does it matter?

Yes.

MS disease modifying drugs/agents are medications (none of which are oral yet) that are FDA approved to reduce the number of relapses (nowadays we generally use the 'annualized relapse rate'); of course, we also hope that these medication reduce disability as well. These medications (Avonex, Betaseron, Copaxone, Extavia, Rebif, Tysabri and Novantrone) are not FDA approved to have any effect on the actual day-to-day symptoms of MS (an MS relapse or exacerbation or attack or flare is when the immune system acts up and there are new problems that usually take a few days to weeks to develop and remain for weeks to months. MS symptoms may fluctuate throughout the day and are caused by past damage to the central nervous system, like muscle tightness or problems walking).

One way of thinking about a disease modifying drug is that it prevents new attacks, while symptomatic treatments help you to minimize the effects of symptoms that are already there. So, if you have no trouble walking, you take a disease modifying drug to prevent an MS flare-up from making you unstable or weak in your legs, while Ampyra is supposed to help you walk better if you already have trouble walking.

This is why I call Ampyra a NeuroFunctional Enabler -- it enables you to function better neurologically. Although the FDA and EMEA are looking at Acorda Therapeutics's (ACOR) pivotal Phase III trials on the time it takes to perform a 25-foot walk, we already know that 4-Aminopyridine helps in so many other symptoms. The argument is that it doesn't simply cover up symptoms by making you feel better, it actually makes you function better because of its mechanism of action. 4-Aminopyridine blocks potassium channels, thereby prolonging action potentials -- the electrical conduction down a nerve that allows us to do everything from walk to speak to think.

So, if Ampyra makes you feel better then why can't in simply be used in lieu of the currently FDA approved disease modifying drugs?

The disease modifying drugs may be frustrating because of how they are given (under the skin, into the muscle or into the vein) and Ampyra may be very attractive because it is new and taken by mouth, but they are used for different reasons and complement (and do not replace) each other. I have written before with some concern of the web searches I have seen with queries such as "Amaya vs. Copaxone" (Amaya was the previously proposed name Ampyra). When I speak to neurologists about this they are surprised because Ampyra and Copaxone are completely different types of medications used for different reasons. This may not always seem so obvious to non-neurologists and the media (in the CNN story the distinction wasn't made entirely clear:

http://www.cnn.com/2010/HEALTH/01/22/fda.approval.ms.drug/index.html?hpt=T2 ), and so Acorda, to its credit, is trying to educate and ensure reasonable and realistic expectations.

So what should you expect from Ampyra (Dalfampridine, nee Fampridine SR)?

Ampyra is supposed to help you walk faster, but it will probably help other symptoms as well (although not yet FDA approved for other symptoms). The nice thing about the medication (at least of the compounded version -- we haven't used Ampyra outside the clinical trials yet) is that you know if it is helping you or not (whether you are a 'responder' or not). This means that it is helping you, you will probably choose to continue it, but if you haven't noticed a change in a long enough period of time, then you will probably look for other treatments (perhaps,Sanofi-Aventis's Nerispirdine, in the future). This is unlike the disease modifying drugs where we say "you won't necessarily feel any different and you won't know if it is helping you, but you should continue to take it because you may have been worse off without it."

Although we usually say that the disease modifying drugs don't help your day-to-day symptoms, some of us believe that by reducing the underlying inflammation in the central nervous system (or even through remyelination or axonal preservation/repair), these medications may also settle down some of the MS symptoms, as well. This is probably seen most commonly in people using Tysabri (Natlizumab) who actually feel better on the drug, not just because they have less relapses.

This raises another concern: Are people with MS (who are not doing as well as they could be doing) going to choose to combine Ampyra with their current disease modifying drug rather than switching to a potentially more effective disease modifying drug (such as Tysabri)? I would like to acknowledge Acorda for trying to ensure that patients, carepartners, families/friends and physicians understand that if someone needs a stronger or different disease modifying drug, Ampyra should not be the alternative.

Remember Ampyra is an Enabler, not a Replacer.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

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