The more information, the better

Screening out?

Biogen Idec (BIIB) has been forced to learn the importance of disseminating information, quicker and better than any other MS company.

That's what having a side effect, such as PML (progressive multifocal leukoencephalopathy) in what was supposed to be a blockbuster MS drug.

PML occurs when the JC virus is reactivated and crosses the blood-brain barrier. The thinking is that if a person who goes on Tysabri (Natalizumab) has not been exposed to the JC virus in the past, then they should not be at risk for developing PML.

The first scientific question is whether this holds true -- if you do not acquire JC virus in childhood or adolescence are you really not at risk for developing PML with Tysabri? Could being exposed to Tysabri make someone more likely to even get infected in the first place with a virus that is thought to be acquired when we are younger?

For the moment we will leave that question behind, as well as the question of what percentage of people in the general population have the latent JC virus : is it 80% as we previously thought, or 50% as new data has suggested?

Will developing a JC virus antibody screen be beneficial to Biogen Idec and Elan?

Firstly, Biogen Idec has prided itself on returning so much of its revenues back into R&D, nd this should be applauded -- so advancing science is always beneficial.

But on a sales point-of-view, I actually think that knowing who does not have the JC virus in their system ill aide the sales of Tysabri. Assuming the test is perfect and that the JC virus is only acquired in younger ages, this would mean that 50% of MS patients are not at risk for PML, even when placed on Tysabri.

This is 50% of the MS market that could [potentially be taken over by Tysabri -- not only in switches as second- or third-line choices, but even as a first-line agent (as it was projected to be back before it was originally voluntarily pulled from the market due to PML. This is a lot larger market share than Tysabri has right now and it can be justified based on the good efficacy data (that looks even better when taking the CLARITY, TRANSFORMS and FREEDOMS studies into consideration -- see:

http://neurologique.blogspot.com/2009/07/merck-kgaa-not-to-be-confused-with.html )

The other 50% of MS patients (those who have been exposed to the JC virus in the past) would be at a potential risk for PML. This doesn't mean that they wouldn't necessarily be placed on Tysabri, but that they are the ones who are at risk -- just as now we think of everyone on Tysabri as being at risk for PML, yet many neurologists and patients choose to be on the medication. So, assuming the 1:1000 risk for PML (simply for demonstrative purposes), then the patient population at risk for PML is actually 500 and so the risk in JC virus antibody positive patients is 1:500 and in JC virus antibody negative patients it is 0:500.

So overall, just as Tysabri patients are willing to assume the risk of PML, the true at-risk MS population of JC virus antinody positive patients will include patients who will be placed on Tysabri despite the risk.

So, the JC virus antinody test will increase the Tysabri market share.

Screening out? No, screening in.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

The two Fs

Better late than never.

Novartis's press release may have been a month after filing the NDA for Fingolimod with the FDA, but it was before something else:

With all the excitement surrounding the imminent Fampridine-SR or Ampyra (Acorda) PDUFA on January 22nd, 2010, Novartis may have used the quiet before the storm of Ampyra to excite analysts and investors about its own big (no, HUGE) news.

Or, maybe it was the JPMorgan Healthcare Conference and the NEJM.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Filing and Timing

Releasing press releases.

On January 20th 2010, Novartis announced that:

1. TRANSFORMS and FREEDOMS were being published in the New England Journal of Medicine (NEJM).
2. It had filed an NDA (New Drug Application) for Fingolimod (FTY720) with the FDA (U.S. Food and Drug Administration) and an MAA (Market Authorization Application) with the EMEA (European Medicines Agency) in DECEMBER 2009.

Huh?

Some may be surprised that Novartis didn't announce this important piece of information when it had filed the regulatory documents, but another way of looking at it is that Novartis did exactly what it said it would:

It submitted the regulatory documents / applications before the end of 2009.

I can't say I was surprised when I heard that the filing had been in December 2009, I just was unable to scoop the news because I also believe in doing what I promised:

To not blog or tweet about the December filing prior to the press release.

Novartis -- I kept my promise, now please keep yours and continue to support the MS community through research and education.

Stay transparent and keep looking for the lowest dose of Fingolimod that is still highly effective while being even safer.

Now we really may see the first Oral MS Drug.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Why now? OR If not now, when?

Why now?

Its understandable that there is a lot of buzz around Ampyra (Dalfampridine) in the MS community, but why weren't the same patients clamoring for compounded 4-Aminopyridine?

I have already written about the advantages of Ampyra over compounded 4-Aminopyridine, but it is difficult to understand why these issues were roadblocks for patients even attempting the medication in the past.

So, why not?

Education.

It seems that a lot of patients didn't know about 4-Aminopyridine and didn't realize its potential as a tool in our arsenal.

Neurologists have also been concerned in using a drug that was unfamiliar to them, not in the PDR and not FDA approved. Variations in the compounding process made many fearful of the potential risk of compounding errors and seizures.

So, not now?

The roadblocks are being removed:

- Education concerning the potential benefits has improved significantly.

- Compounding errors are a moot point.

The question becomes: whether the risk for seizures has been eliminated or not?

Only time will tell whether seizures are relevant or not now.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

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

info@neurologique.org
www.neurologique.org

Congratulations ... to YOU!

In the midst of the devastation in Haiti, MS patients have a reason to celebrate ...

... Fampridine SR (Dalfampridine / 4-Aminopyridine) is FDA approved as Ampyra.

Acorda's (ACOR) drug to be manufactured under licenses from Elan (ELN) will end the debate over who which drug will be the first oral medication for MS.

It is not Merck KGaA / EMD Serono's Cladribine (Mulinax/Movectro) or Novartis's (NVS) Fingolimod (FTY720), it is Acorda's neurofunctional enabler, Ampyra.

So, who are the stakeholders and how did they do?

Acorda ... won

Investors ... won

Patients ... won !!!!

Compounding pharmacies ... lost

My job now is to figure out the root of the word Ampyra (see my earlier blog on the sources for Amaya).

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Haiti and Neurologists

All of our hearts go out to those devistated by the natural disaster in Haiti.

What some of the readers may not realize, is that neurologists are taking an active role, not only in advocating for their patients (seee www.neurologique.org and ustream.tv/neurologique for videos on neurologists training to be effective advocates), but are also trying to board ships and airplanes headed for Haiti.

Neurologists, eith our training in TBI (traumatic brain injury), headaches, seizures, etc., are ideally suited to help in these important relief efforts. The Neurology community can contribute, not only in the general sense of physicians/doctors who have dedicated their time and expertise, but as advocates to those affected by the earthquake in Haiti.


In the midst of devastation, we all stand together.


- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MS in the News: Medical marijuana

MS in the News: Good or Bad?

http://www.nytimes.com/2010/01/12/nyregion/12marijuana.html?sudsredirect=true

In response to a recent New York Times article, I wrote the following Letter To The Editor

Dear Editor:

As an MS specialist and the President-Elect of the Florida Society of Neurology, I read with great interest David Kocieniewski's January 11, 2009 article: 'New Jersey Vote Backs Marijuana for Severely Ill.' While my patients and I appreciated the special focus on Multiple Sclerosis (MS), we were concerned by the imprecise statement by one of the interviewees, Mr. Kwiatkowski, that “The M.S. Society has shown that this drug will help slow the progression of my disease. Why would I want to use anything else?” We would have appreciated it if Mr. Kocieniewski would have verified that the National MS Society has never shown this to be the case. There are, however, ongoing trials studying this question, but the results have not yet "shown" that marijuana slows MS progression,. In fact, after many well designed clinical trials, there is still no medication (allopathic or complementary), which has been shown to slow MS progression (as opposed to multiple medications that reduce relapses). In the future, we would appreciate it if your writers would verify medical statements with the physician community.

Thank you

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org