Oral DMD’s – Will they really be the answer?

[Lulu54]

A local neurologist, Dr. Alan Jacobs, gave a presentation at a Shared Solutions/TEVA Pharmaceuticals dinner the other night on the subject of Oral MS drugs.  He titled his talk OVER THE RAINBOW, wanting to remind all of us that the things we wish for maybe aren’t always as good as what we already have.

Dr. Jacobs warned that we are going to be bombarded with oral drug options in the next few years, and as the patient consumer, we need to understand what that fully means before rushing in to drop our syringes in favor of a pill.

Currently we know that our CRAB’s work – Copaxone, Rebif, Avonex, and Betaseron; they have been around for over a decade and some are approaching 20 years in use, and we fully understand the drug actions and their side effects.  The oral drugs that are being proposed are a different story, we don’t yet have a track record of their performance and side effects.

His talk was loaded with statistics, most of which I didn’t copy or comprehend, so I won’t be sharing that here.  What  I do want to relay are some key points he made –

There are over 390 treatments being studied for adoption across the world and that is a heck of a lot of research going on.  Many of those drugs quickly fall out of study for a variety of reasons.   The vast majority of these trials are for drugs that are already in use for other diseases.  

We have a great concern about the use of Tysabri, the non-CRAB drug that is used as a last resort for MS patients who haven’t responded to other treatment, because of the possibility of PML , Progressive Multifocal Leukoencephalopathy. There have been a handful of PML cases reported among Tysabri users.    

PML is also listed  as a possible side effect of many of the oral meds that are in the FDA pipeline for approval.  

The front-runners of the  oral meds are showing dramatic results in the reduction of relapses, lesion load, and slowing of brain atrophy.  On the surface, this is promising news.  The rest of the story, though, is not necessarily so bright.

Many of these drugs are already in use as chemotherapy treatments, and I’m sure you understand the basics of their toxicity.  Many of these drugs work by taking out the T cells and then also suppressing the B cells.  I’m not a researcher, so I have to take Dr. Jacob’s word for it that this can sometimes not be good.  You aren’t just targeting those cells that work on the MS, but altering all of them, which can impact other functions in our bodies.


Dr. Jacobs reviewed the studies of many of the oral meds, and here I have compiled a list of commons side effects that are known so far – a large number of these apply to all of the drugs in question and some to just  a few.  

Safety and tolerability factors –
The potential to develop an autoimmune disorder , Central Nervous System opportunistic diseases or PML top the list.  

Then comes the reports of ITP, Thyroid  (hyper and hypo), Graves Disease, Renal failure, and assorted infections.  After these were even more assorted side effects such as GI problems, headaches, nausea.  

This also helps to explain the study that DV posted about neurologists predicting that they will NOT be prescribing oral drugs to existing patients and mainly using them on new patients or ones who will not do their own injections.  
As stated early on in this, we know what we are dealing with in taking a CRAB, but the oral meds will begin a whole new cycle of learning.  

Those oral meds aren’t sounding quite so good at this point to me, how about you? We might just want to stick with our needles for a while longer.  



Here is a recap of some points about the particular drugs by name/study:

The first drug he discussed was Laquinimod, which is a derivative of the drug Linomide.  There are 60 different forms/structures of Linomide, including Laguinimod.  Laquinimod was studied in the ALLEGRO and BRAVO studies, and Dr. Jacobs said that there was not as significant improvement as they had wanted to see.  Currently it is on track to be released in 2011.

CLADRIBINE will be the first of the oral meds to be released, either this year or by 2010.  It is currently an IV drug used for Hairy Cell Leukemia.  It was studied in the CLARITY study and will be reported on next week in Seattle.  There are 4 known cancer cases associated with patients in this trial.

ALEMTUZUMAB – takes out the T cells and the B cells

CAMMS223 – shows dramatic results with brain volume and lesion load, but has multiple safety issues, including reports of PML

BG12 – Dimethylfumerate – is a psoriasis drug.

FINGOLIMOD is also a kidney transplant rejection drug

RETUXIMAB is a B cell therapy and uses an active virus to deactive the disease (I’m not sure if I have this one right)

[Lulu54]

Engineer just posted the BBC link to this story - and I thought it appropriate to add it here....

http://news.bbc.co.uk/2/hi/health/8023120.stm

[Erin0313]

Lulu,

  Here here ! I am calling on all of the great scientists around the world to buckle down and find us a cure!!!

Raising money and awareness seems to be very important if this will happen in our life time.

Take Care
Erin :)

[Lulu54]

I didn't read anything into your post - you add a great part to this discussion since you are actually on one of these future treatments.  The main point I want to relay here is we spend so much time longing for that option that isn't the CRAB injections, but need to understand that there still is no perfect answer.  

Erin, your information just reinforces what I was trying to share.

I'm holding out great hope for the myelin repair work, myself!   I don't want just band-aids put on my illness, I want a cure!  LOL

[Erin0313]

Lulu,

  Thanks for sharing and for all of the hard work that you put in on various topics.

  When I read my post again it sounded a little like MEOW. If that is how it came across I am so sorry. I was just sharing since I am on one of the drugs that will soon be mass released. I was not trying to sound like I was preaching or correcting.

Your a doll. Thanks again

Erin :)

[Lulu54]

If I had editing power, I would change the title of this to

ALTERNATIVES TO CRAB THERAPY and take out the mention of oral drugs in title to lessen the confusion.  :-)

They covered all of these drugs currently  being tested, and that included IV drugs.  

What I have written here is not meant to be equal to a good discussion with your doctors about DMD options . it is just my attempt to start a conversation here about how this next wave of MS drugs is going to be marketed to us as well as how they may affect us.  

I find it very encouraging that there will be more options for patients who can't tolerate any of the CRABs.  There are several of you here who have that problem, and it has to be extremely disheartening to be in that position.  

Again, if any of you have the opportunity to attend one of these presentations (I know all of the drug mfgs. host them all over the country, not just TEVA) please take the time.  It was very informative.  

as always,
Lulu

[Erin0313]

Lu,
  
  Just thought I would chime in since I am on Rituxan - bottom of your list Retuximab. Mine is not an oral but an IV therapy and it is in clinical trials for MS but is now approved for RA and was first used (still is) for non-Hodgkin's Lymphoma.

  Rituxan modulates B cells and yes one of the scary things is PML. Most cases of PML were in patients with systemic lupus but it can happen to any one taking it.

The other most dangerous effect is if you have a tumor, the tumor is attacked and overwhelms the body -called tumor lysis syndrome causing renal failure.

I was put on it because the other DMD's were not helping my MS and I "qualified" because of the RA dx. I have 2 neuro's and 1 rheumy that said they felt better using this than Tysabri.

2 follow up MRI's show very little progress with my MS which is the first time since being diagnosed and MRI report said stable, but I am having all kinds of other issues like anemia & staph infection etc. It's like the MS and other auto-immune disease just fight and go back and forth attacking me.

I am due to have my next infusion in May but even with "good" MRI findings I am having major doubts about the safety of this drug and what else is happening to my system while I am on it. I'm going to discuss with both neuro's before I allow another round of treatment.

P.S. The side effects right after are like chemo - bone pain, puking, chills etc for about 3 days each time, yuck.

That's my 2 cents. In the end we all have to choose for ourselves - Take Care

  Hugs,
  Erin :)




Erin :)

[willowwoman7]

I was asked to take a survey about some of the new oral dmd's and the way they would be presented, asking me if I would be willing to try one of them. Frankly? No, I would not. They each have black box warnings on them, one of them (I can't remember which one, they may not have said) has had 5 deaths attributed to it. And each one is not advised for anyone with vascular problems which leaves me out by having lupus. But you know what? After doing that survey, I don't think I would take them even if I could.

[Lulu54]

I looked back at my notes and he specificially talked about PML with the CAMMs study - just going by what was said.

[Lulu54]

I should have added there that even though this was a TEVA/Shared Solutions dinner, they were definitely being impartial toward the results.  It was the TEVA drug that the said showed mixed results and were disappointed in the outcomes of the trials.  That is part of why it is now delayed to 2011.  

these neuros are associated with a local college medical school, see about 1,500 MS patients but are not MS neuros.  They do particpate in almost all of the trials that are going on, and did a good job of giving the impartial report.  Interestingly, they commented that soon the day will come that gneeral neuros and PCP will not be able to dx and treat MS - there will be too many options and it will definitely take a specialist to make informed recommmendations for treatment.

PatientX, as I said, this was just a lump grouping I have listed, off of my very rough notes scribbled while I tried to listen and read the presentation slides.  You areright about the couple IV drugs.  The side effects I listed come up in some of the drugs but not necessarily all of them.  The examples were given to show us that perhaps being on CRABs is not such a bad thing right now after all.  There are other options that will be out there soon  if someone can't tolerate the CRABs.

If anyone gets a chance to go to one of these types of presentations, by all means go.  It was not a waste of my time, even though it left my head spinning.
Lu

[patientx]

I was thinking the same thing.  Especially since it sounds like Laquinimod, Teva's attempt at an oral med, isn't doing so hot.

Alemtuzumab (Campath) and rituxamab are not oral meds; they are given by IV.  I don't believe any cases of PML have been reported in the Campath CAMMS223 trial.  In fact, no persons treated with alemtuzumab for MS have contracted PML.  The very few cases were in people treated for leukemia.  ITP is a bigger concern with Campath, but it is treatable.

Rituximab is a monoclonal antibody.

[jensequitur]

Interesting - thanks, Lulu!

I have to wonder how impartial this doctor is, as it was a Shared Solutions conference!