4-AP Question for Wise!

[JWJR1970]

Wise I just read about 4-AP on here and this is the 1st time I've ever heard about this in 22 years of being in the wheelchair. Is it really safe to take? I'm a very interested in taking it. My Dr. is pretty open minded so I think I can get a prescription for it. I'm a c6-c7 sci. Thanks!

[Wise Young]

Originally Posted by JWJR1970

Wise I just read about 4-AP on here and this is the 1st time I've ever heard about this in 22 years of being in the wheelchair. Is it really safe to take? I'm a very interested in taking it. My Dr. is pretty open minded so I think I can get a prescription for it. I'm a c6-c7 sci. Thanks!

JWJR1970,

Many people with spinal cord injury have been taking fampridine over the past 20 years, from compounding pharmacies that will provide an "immediate release" Fampridine 5 or 10 mg capsule upon prescription by a doctor. Some pharmacies also provided a formulation called sustained release but I am skeptical that this is a true sustained release but simply a version that resulted in lower doses being absorbed. The word-of-mouth recommended dose for the treatment was 10 mg four times a day, i.e. every 6 hours. Some people have reported that the treatment has more side effects in the beginning and therefore recommended that the dose be ramped up over a period of 2 weeks to allow the body to accommodate to the drug.

So, many people would start with a 5 mg dose once a day. If they do not have any significant problems after a day, they advance to 5 mg every 12 hours. If no problems, then 5 mg every 8 hours. If still no problem, then 5 mg every 6 hours. If no problems, they exchange one of the 5 mg capsule with a 10 mg capsule. If no problems, they then exchange more of the 5 mg capsules with 10 mg capsules until the are taking 10 mg four times a day. If there are complications, such as nervousness, tingling sensations, insomnia, and other problems, the person does not progress to the next dose. The treatment effect should be apparent within a few days after the person has reached the highest tolerated dose. If no beneficial effect is seen within a week, the patient should stop taking the drug by ramping down the dose in reverse over a period of a week or two.

Acorda Therapeutics (by the way, I am a founder of the company, am on its Board of Directors, and own stock in the company) has developed a sustained release version of the drug. It tested the sustained release formulation in people with spinal cord injury from 1997-2007, Unfortunately, two phase 3 clinical trials that showed that the drug has no significant effect on spasticity. Spasticity was the primary outcome measure of the trials. This may be because the drug is effective only in about a quarter to a third of patients with spinal cord injury, the trial used the wrong outcome measure, and the trial allowed subjects to take baclofen and other anti-spasticity drugs during the trial. Acorda then went on ahead and showed that Fampridine significantly improved walking in patients with multiple sclerosis. In the past two years, Acorda completed two pivotal phase 3 trials indicating the Fampridine SR significantly improved walking in people with MS.

The Food and Drug Administration (FDA) is now considering the treatment for approval. The FDA has scheduled a Fampridine SR Advisory Panel meeting on October 14, which will issue its report. On October 22, the Peripheral and Central Nervous System Drugs Advisory Committee (PDUFA) will meet. One week is too short a time for the committee to issue a formal approval. So, it is not clear yet when the drug would be available to the public. Please note that if the drug is approved, it will be only for multiple sclerosis. The company cannot and should not encourage physicians to prescribe the drug for people with spinal cord injury. Fampridine SR may not be available from Acorda for several months.

Yesterday, Acorda presented data on a two-year extension study of 283 subjects, at the 25th Congress of the European Committee for Multiple Sclerosis (ECTRIMS) in Düsseldorf, Germany. They found that the 25% of the MS subjects deemed to be responders in the original trial continued to exhibit improved walking. The retention rate in people continuing to take the drug in the trial extension is high at over 70%, even in those patients that were classified as non-responders. These data suggest that the drug is continuing to exert beneficial effects beyond just walking and over a 2-year period. The seizure rate on the drug is 0.35±0.15%, not different from the rate expected from the general population of patients with MS.

You can wait or go with the compounding pharmacy formulation.

Wise

[Sue Pendleton]

[quote] Acorda Therapeutics (by the way, I am a founder of the company, am on its Board of Directors, and own stock in the company) has developed a sustained release version of the drug. It tested the sustained release formulation in people with spinal cord injury from 1997-2007, Unfortunately, two phase 3 clinical trials that showed that the drug has no significant effect on spasticity. Spasticity was the primary outcome measure of the trials. This may be because the drug is effective only in about a quarter to a third of patients with spinal cord injury, the trial used the wrong outcome measure, and the trial allowed subjects to take baclofen and other anti-spasticity drugs during the trial. [/unquote]

Did you speak with Naomi Kleitman on day 2 at W2W, Wise? Betsy, she and I were discussing the possibility of 1 main and 2 side end points in FDA trials as both Acorda and Fidia chose wrong end points (at least as far as Betsy and I were concerned). The drugs worked but the trials failed based solely on the current FDA requiement for 1 end point.

[MzzzKathee]

Would you clarify this comment: "cannot and should not encourage physicians to prescribe the drug for people with spinal cord injury" I understand the cannot but... should not?

[Wise Young]

Originally Posted by MzzzKathee

Would you clarify this comment: "cannot and should not encourage physicians to prescribe the drug for people with spinal cord injury" I understand the cannot but... should not?

I am a Director of the Acorda Therapeutic and the company should not enourage off-label use of the a drug. Pfizer recently had to pay a $2.3 billion fine for encouraging off label use of several of their drugs (Source)

Wise.

[MSWIFE1]

My husband has MS, 1st attack 7-05 effected his right arm, that went away, 2nd attack 10-05 effected his bowels, in one weeks time, lost use of left arm, both legs, bowel, bladder, sight, ability to talk, eat, and breath. Over the last 4 years has regained some sight, ability to talk, eat and breath. Has controlled movement in his right leg, and left arm. Trunk control really good. Movement in his left leg comes and goes. Right arm works fine. Has SP cath for bladder and bowels are moving fine with no program, just can't control as to when. I have been watching the reports on Acorda for some time now and have really sparked an interest. Oct. 14 is quickly approaching and I have hopes that Fampridine SR gets its much needed approval. My question is, do we think if will really help someone such as my husband who is unable to walk at all?

[Wise Young]

Originally Posted by MSWIFE1

My husband has MS, 1st attack 7-05 effected his right arm, that went away, 2nd attack 10-05 effected his bowels, in one weeks time, lost use of left arm, both legs, bowel, bladder, sight, ability to talk, eat, and breath. Over the last 4 years has regained some sight, ability to talk, eat and breath. Has controlled movement in his right leg, and left arm. Trunk control really good. Movement in his left leg comes and goes. Right arm works fine. Has SP cath for bladder and bowels are moving fine with no program, just can't control as to when. I have been watching the reports on Acorda for some time now and have really sparked an interest. Oct. 14 is quickly approaching and I have hopes that Fampridine SR gets its much needed approval. My question is, do we think if will really help someone such as my husband who is unable to walk at all?

MSWIFE1,

I do hope that the FDA will approve fampridine. It has been a long time and the company has worked its heart out to get the drug ready for approval. In my opinion, this is a drug that everybody with MS should try. Its effects will vary from person to person because it depends on how many axons are there and the demyelination state of the axons.

The clinical trials were very difficult to carry out because everybody will respond to Fampridine in a different way and there is no single outcome measure that could be used for everybody. Acorda chose to use walking as the primary outcome measure and that turned out to be highly significant.

What is most interesting is that nearly 80% of the people who were in the trials chose to remain on the drug after the trials for the past year. Not all the patients who chose to remain on the drug had improvements in their walking. Yet, they chose to continue taking the drug.

The reason is probably because they are finding other benefits from the drug besides walking. Perhaps it is less fatigue. A friend of mine with MS told me that reduction in fatigue was the reason why he used the drug since 1991. For some, it may be because it improves sensation and sexual function.

Because the effects should be apparent within days, most people should try for a week or two, to see what effect it might have. If the improvement is worth it, people can continue it. If not, they can stop.

Wise.

[MSWIFE1]

Thank you for your quick reply. My next question is - if the SR doesn't get approved should we still get a prescription for Fampridine and if so how many mg, etc.?

[Wise Young]

Originally Posted by MSWIFE1

Thank you for your quick reply. My next question is - if the SR doesn't get approved should we still get a prescription for Fampridine and if so how many mg, etc.?

MSWIFE1, let's cross that bridge when it comes in about two weeks. Wise.

[Geoman]

Wise, Are you able to make any comment on 4-AP and potential neuopathic pain reduction. I did read something where you mentioned this potential a while ago in regard to re-myelination. Also, do you know if it is likely that we would be able to be prescribed 4-AP (if FDA approved) in Australia, either through the US or direct in Australia.

Thanks for your time and effort, as always, it's much appreciated.

Clayton