This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi there,

Can anyone adequately explain why it is going to take another 10 years before HSCT is approved by the FDA, when trials have been going on for sooooo long as it is? Do they really need to track the patients for ten years post infusion? It seems to me that these drugs are already being used for blood cancers and are known pretty well. Also it doesn't seem like the same length of time is given to other drugs, such as BG-12. That seems to have come through phase III in about 5 years and is about to get FDA approval.....

Any enlightenment would be great!!!

A bit of conspiracy theory. HSCT is a single procedure, no drugs are required after that. And that is something that the pharmaceutical companies hate. They want you on drugs all your life, and they are doing everything they can to block real cures. They insist that the tests are not double blind, but it is impossible or at least not ethical to make a double blind study with such method. It is not a pill that you take, and one is sugar, the other some chemical. From what I last red new drugs go on the market after 6 months of trials now, and 15+ for HSCT is insanity to me. And keep in mind, that the drugs for MS are one of the most expensive. Also HSCT can be used to tread Diabetes, and that is something that no company want's. All the cash cows that are buying insulin will stop, and that is not good for the shareholders....

Thanks Pesho, that HSCT can't be double blind makes sense, but as you say, it's still such a long time regardless of the type of trial... I totally agree that pharmaceutical companies don't want to actually cure anyone outright nor do they want anyone else to cure anyone, but do they have the power to actually hold-up Dr Burt's trial? Surely that is in the hands of the FDA?

I guess they will have another ten years of making bank on the DMD's which are ridiculously pathetic when compared to HSCT.

From Nature:

"...Since then, Burt and others have demonstrated the therapeutic potential of haematopoietic stem-cell
transplantation (HSCT) for MS and other conditions. In HSCT, blood-cell precursors (HSCs) are purified
from a patient's own bone marrow. The patient then undergoes a 'conditioning' chemotherapy regimen that
heavily suppresses or even wipes out their defective immune system. The stem cells are then transplanted
intravenously back into the patient, restoring immunity. The results have been remarkable: in many studies
at least 60–70% of transplant recipients achieved relief from MS progression, and it seemed to last far
beyond the initial treatment1. “In 10 years, we have never seen a renewal of inflammatory disease activity
in any of our successfully treated patients,” says Mark Freedman, a neurologist at the University of Ottawa
in Canada who has extensive experience of HSCT clinical trials.


Practitioners see HSCT as a powerful way to help patients with aggressive forms of MS that have been
resistant to standard drug regimens. But it is not a therapy to be taken lightly. Severe side effects include
loss of hair and fingernails, as well as premature menopause for female patients. “The regimen that we use
is completely myeloablative — it's a standard bone-marrow transplant, and it's no cakewalk,” says
Freedman, “but the trade-off is years and years of not needing therapy.” Burt's group has instead opted for
a more moderate conditioning regimen that does not completely eradicate the patient's bone marrow.
Results suggest that this gentler approach can reduce the toxic effects of treatment without significantly
undermining its efficacy. ...


Even with HSCT, which has been successfully performed in several hundred patients worldwide, clinical
trials have been limited to individual research centres assessing a few dozen patients. This has led to a
confusing patchwork of studies that are virtually impossible to compare with one another. “It's a dog's
breakfast,” says Freedman. “Different conditioning regimens, different choice of patients, different types of
follow-up — it really doesn't help us to have all these different approaches.” ...

“MSCs are probably not as good at intense immunosuppression as the [HSC] treatment, but at least in
animal studies, it's been demonstrated that the ability of MSCs to foster repair is certainly much stronger,”
says Uccelli. Although such stem-cell therapy is unlikely to displace front-line immunotherapeutics, it might
offer a promising middle-ground therapy before committing to the rigours of HSCT. “There's no
bone-marrow suppression or chemo poisons, you're simply putting in a cell product,” says Freedman, “and
since they don't get rejected, you don't need anti-rejection medicine.”..."

Every drug and/or medical procedure in the US must go through the same steps to become approved by the FDA in the United States. However, not every application will take the same time. The time is strongly dependent upon how long it takes to establish the measured clinical outcome as originally defined by the applicant. So the Government does not specifically determine how long it takes for approval. That is dictated predominantly by the science, the complexity of recruiting patients that meet the pre-defined inclusion/exclusion criteria (very narrow for the NWU HSCT trial with Dr. Burt), the methods used for testing and the time requied to follow up patients to support that statistcical conclusions. This takes longer with a medical procedure like HSCT as compared to drugs because the result & magnitude of effect is not fully apparent until years after completion of the procedure.

Here's how HSCT has been progressing through the necessary steps to become FDA-approved.

Phase I clinical trial (small population to prove the treatment is "safe" and "tolerable") = 2 years, CY 2000-2002: Completed

Phase II clinical trial (slightly larger non-randomized population to demonstrate efficacy) = 8 years, 2003-2010: Completed

Phase III clinical trial (larger treatment population with randomization) = 8 years (est.), 2011 - 2019: Ongoing

Final report and preparation of FDA submission = 2 years, 2020-2021 (est.)

In FDA review commitee = 1-2 years, 2022 - 2023 (est.)

Estimated final FDA approval = 2022 or 2023

So, 10+ more years . Think it is better to do it now, rather than wait. In 10 years who know what will happen with your MS .

There's even more to it than what George says, because some drug companies can put up huge bond and have their drugs fast tracked through the FDA. Crony capitalism at its worst. I am a huge free market guy, but when govt stacks the deck for their friends, it is really depressing.

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?

This is the way that all the drugs go through to get approval. HSCT is not a cake walk. It has an approximately 70% of success rate with a high mortality rate of 2-3%. Patients undergo a 'conditioning' chemotherapy regimen that heavily suppresses or even wipes out their effective immune system.

It is not known which groups of patients benefit from the treatment. It is not known whether renewal of inflammatory disease activity will occur in the long run. Also not known what will happen with the neuro degeneration process which seems to be independent from deregulated immune cells and it is a characteristics of the progressive stage. This process might start 15 or 20 years after the onset of the disease. There is no such a long term data available at the moment.

It is not a coincidence that currently, neurologists are not recommending HSCT for those RRMS patients who are doing well (even though they would benefit the most from the treatment) and responsive to drug treatment.

Chemo has lots of serious long-term side effects:

Cataracts
Early menopause
Heart problems
Infertility
Liver problems
Lung disease
Osteoporosis
Reduced lung capacity
Increased risk of other cancers


”Chemo Can Actually Cause Cancer”
Monday, August 6, 2012 6:59 AM

”Researchers in the United States made the "completely unexpected" finding while seeking to explain why cancer cells are so resilient inside the human body when they are easy to kill in the lab.”

Good points gogo. I read a recent medical article that said the some doctors have identified a cancer related stem cell that is very twilight and can hide in the body for years or be behind some latent malignancies. It may even be responsible for cancers that don't respond to chemo in the body like they do in the lab. At the same time, tysabri causes pml, gilenya causes peoples hearts to stop randomly, and 3 of the four crab drugs cause long term liver damage. The way se Burt explained it to me was that if you were going to tak a risk to treat your disease, why risk dying to slow it down when his program hasn't lost a peron in over 12 years and has had a complete stoppage of the disease progression. I don't know what is in store if I am able to get the treatment, but I know the effects of waiting 20 years and having 5 or 6 relapses per year.

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?

You made a good point about currently available drugs. I think everyone's situation is different. The funny thing is that RRMS patients at early stage can benefit the most from HSCT, but those patients are the ones who might never accumulate any major disability with MS as approximately 1/4 of RRMS patients will never go to SPMS. However, circa 25% of the treated patients will not benefit from HSCT while paying a hell of a lot money for the treatment and in the meantime they get infertility and other things while also risking their lifes. So, to me it just does not seem a no-brainer to chose HSCT. Huge financial risk as not everyone succeeds and besides that you are almost sure to conract some side effects. ...and there is that mortality rate...

Of course, if someone succeeds in the long run, then he made a good decison.

Good call.

I beleive that it should be reserved for those that qualify as "agressive" in their progression. I know that I have had multiple relapses and multiple new spinal lesions i the last year, and according to the study, that turns dont the vast majority of people who apply, I am a good candidate. I have a buddy who is a police detective, and he hasnt had a relapse in 8 yrs, has one brain lesion, and has been on rebif and doing fine. It would be dumb to reccomend this treatment to him, but I am the guy that qualifies, so i am seeking the best option for me.

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?

I watched some documentaries recently and they mentioned that new drugs come after only 6 months of clinical trials in the US. And that the real trial is in the public when people start dying. Drug companies pay the FDA big money and they push forward their "inventions". So waiting 30 years for HSCT to become available is a crime in my eyes. Yes, it has risks, but the illness is not like a cold. Just it is not a money cow for some big pharma and will kill big money for them. Having 75% chance to move out of RRMS sounds a lot worse than the chance of getting cancer or dying. And the mortality rate now is <1%, way lower than MS itself. I might get infertile, but in this condition now I don't really want a girlfriend at all, because I have problem walking stairs sometimes, walking on flat surface is not a problem at least for now. Just the money are way too much, but I will try to get over that.

Say it brother.

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?