Thank you very much. That was perfect.
I am Durhane Wong-Rieger. I am actually the volunteer president of the Canadian Organization for Rare Disorders.
CORD is a national network of patient organizations and groups representing Canadians who have rare disorders. There are about 5,000 to maybe 7,000 rare disorders in Canada, which affect, we believe, up to 10% of the Canadian population. Most of these disorders do have a genetic base. Most of them affect infants, children. CORD's mission, then, is to provide a common voice for those affected by rare disorders, and we do education, support, and advocacy.
I optimistically entitled my presentation to you—which I apologize for not having in front of you—“How Canada's Common Drug Review is Failing Patients With Rare Disorders and How to Fix It”.
In the decade before 1984, there were about 34 new drugs for rare disorders, in that entire decade. In the two decades since 1983, when the United States passed the Orphan Drug Act, there have been more than 300 new therapies introduced, approved for patient access. Similarly, since the European Union passed their orphan drug act in 2000, there have been more than 30 new therapies approved for market access in Europe.
The reaction from our patients and from health care providers has been one of hope. We hear oftentimes, “Thank goodness we finally have a chance for life. Hopefully, there will soon be a therapy for our condition.” We contrast that with the reaction from our drug plan gatekeepers, who tend to say, “Oh my gosh, how can we afford this? And how many other therapies are there in the pipeline?”
Therein lies our conundrum. Patients anxiously await each new therapy because it offers them a chance for life, and what we get are drug plan managers who view each new approved drug as a cost centre threatening to overrun their already oversubscribed drug budgets.
What we would like to maybe move to is to talk about what would be the desired outcomes of an effective drug review process for rare disorders. I think what we would want to see is that in fact Canadians with rare disorders would have the same access to new therapies as those with more common ones.
It means that those with rare and oftentimes severe and life-threatening disorders would receive therapies that are equivalent to the standard of care and best practices of other countries; that therapy would be approved and available for patients similarly through the public and the private drug plans, and they would be based on evidence of safety, effectiveness, and tolerance.
Importantly, we would expect that therapy be made available to appropriate patients based on some reasonable extrapolations from the available evidence, and we would want to see timely feedback on real-world safety and effectiveness for each patient, as well as a collection of aggregate information that would advise all stakeholders, including patients and health care providers, as well as the regulators and manufacturers, in terms of their longer-term effectiveness and safety.
Sadly, what is the current status? It is a sad but true fact that Canadian patients with rare disorders have probably the worst access among all patients in the developed world to new therapies—and I don't say that lightly. These are often treatments for severe, debilitating, and life-threatening disorders, sometimes the only treatment.
What are some of these new therapies? There are therapies such as the treatments for metabolic disorders, for Gaucher disease, and what we've heard recently a lot about, Fabry disease, MPS, and now recently Pompe disease, all severely debilitating, life-threatening disorders that now have a treatment available.
There are treatments for rare blood pressure and blood disorders. For pulmonary arterial hypertension, the first new therapy, the first therapy ever, was introduced in 1995; now we have three therapies available. Hemophilia, thrombocytopenia—these are all newer therapies that can improve clotting with less risk.
There are treatments for pituitary, thyroid, and parathyroid-related diseases. One of the ones that we've recently had introduced in Canada, which in fact was rejected, is a treatment for acromegaly, which untreated would cause gigantism.
Many of the disorders that are rare are childhood disorders, and we're now seeing, for instance, for the first time, new treatments for childhood leukemias.
About one third of these orphan drugs are for some rare forms of cancer.
Unfortunately, in our experience, the common drug review process is inherently biased against what we call “orphan drugs”, these drugs for rare disorders. The pharmaco-economic process that is used by the CDR relies often, and almost exclusively, on large-scale randomized clinical trials, and clinical trials that have long-term evidence in terms of benefit. That is patently impossible when you're talking about a rare disorder, which has very small patient groups available for clinical trials.
Also, we do not have the long-term evidence. Often we don't know a whole lot about the natural state of the disease, and we certainly have not had the drugs long enough to collect the long-term evidence.
As evidence of the fact, of the 11 drugs submitted for rare conditions since the CDR has been in business, all of which are for debilitating or life-threatening disorders, almost every single one has been rejected. These are all drugs, interestingly enough, that are available to patients through public drug funding in most other developed countries, and even in developing countries.
These drugs include Somavert, for gigantism; Replagal, for Fabry disease; Fabrazyme, for Fabry disease; Amevive, for chronic pIaque psoriasis; Aldurazyme, for MPS I; Zavesca, for Gaucher disease; Forteo, for a rare form of osteoporosis; three drugs—Sensipar, Nexavar, and Sutent—for rare forms of kidney cancer. The last one, Exjade, is for transfusion-related iron overload, which actually just this past week, we were notified, had a recommendation for very limited use.
The result is that we end up with this two-tier process. All of these drugs, interestingly enough, are available if you have a private drug plan, the kind of private drug plan most politicians and bureaucrats who are actually managing this process have access to, but that anybody on a public drug plan does not have access to.
Sadly, to the best of my knowledge, there is no drug for a rare disorder being paid for currently by a Canadian public drug plan that has not been put on the plan without some strident patient advocacy. Despite what most people believe, patients do not like to go through this process.
We end up also with some very bizarre kinds of things happening. I think of Naglazyme, a treatment for MPS VI that the manufacturers chose not even to submit. Through advocacy, it is being paid for by the Ontario government, though now only available through a special access program. It means there's no safety monitoring, no ongoing monitoring of the drug.
The same thing happened with a recent case in MPS II. Elaprase is a drug still going through Health Canada. There was advocacy on the part of the parents. B.C. said yes. Interestingly enough, in two cases in Ontario, the Ontario government said no, let's wait.
We've seen this happen with regard to AIDS drugs and cancer drugs, where strident advocacy was required. We would submit that if the CDR had been in place when the first AIDS drugs came into use, they would have also been rejected by the CDR, and in fact all of those patients would have been experiencing the same fate as many of our patients with rare disorders: they would have just died.
There are some other very bizarre things that I want to point out to you in terms of how this CDR process actually doesn't work.
Zavesca, for Gaucher disease, is a second-line therapy, a first oral therapy. The first-line therapy Cerazyme was introduced about ten years ago as the first breakthrough therapy for this type of lysosomal storage disorder. Zavesca was turned down by the CDR. They said it didn't have enough evidence and it cost too much.
The irony of it is that in fact it came to the CDR with better clinical evidence and cost less than Cerazyme, and yet it was still turned down. So we know that if Cerazyme had been introduced today, none of those patients would have gotten access, and the ten-year data we now have for Cerazyme, which demonstrates definitively that it's effective—All of those patients would have never been on the treatment. Many of them would have died.
We know that too because, as I mentioned, three other enzyme replacement therapies similar to Cerazyme have been systematically turned down by the CDR as having not enough long-term data and not enough evidence of statistical significance, objecting to the use of surrogate markers in terms of long-term clinical outcomes.
I'll give you one final example, which we think is very bizarre. That's Nexavar. This is one of the kidney drugs that were turned down. I think it's really bizarre, because in my opinion it was turned down because the evidence was too good.
What happened with Nexavar? In phase three clinical trials, interim data was coming through showing very clearly that the drug was effective. The U.S. FDA suggested that patients who were on the control arm for ethical reasons be given an opportunity to cross over to the treatment arm. Many of them chose to do that.
Well, lo and behold, by the time the clinical trials were concluded, we did not have enough patients in the control arm to actually achieve statistical significance to say that the drug was more effective than the placebo.
The U.S. FDA got it; the European Union got it; even Health Canada got it. They all approved the drug. The CDR said no, thank you, that they didn't have sufficient evidence of long-term clinical benefits, and they could not seem to understand that there was no way that evidence was going to be forthcoming.
The CDR has said repeatedly that they know these longer-term trials could be done, because they've seen evidence from the Cerazyme example. We now have longer-term evidence from the Fabry disease for drugs that have been approved and are available elsewhere. They're saying, fine, do the long-term studies. We're saying it is unethical to expect that patients in Canada will wait 4 to 10 years while these trials are being done, while patients have access elsewhere in the country. And quite frankly, once the drug has been approved through the clinical trials and is available elsewhere, what motivation is there for any company to do this kind of clinical trial for our very few rare-disorders patients? It means that our patients end up being the control group, quite frankly. I think we are very concerned about what's happening in terms of the trend here.
It is our opinion, though, that we could in fact have a much more effective process. Interestingly, we do not disagree that publicly funded health care programs should assess drugs and other technologies for safety, efficacy, and even cost-effectiveness. Moreover, we agree there should in fact be randomized control trials where possible. However, we think these trials have to be appropriate to the patient population, and the standards that are used have to be appropriate.
Internationally, there have now been agreed-upon standards by which you would actually do clinical trials with small patient populations. There's international agreement around what surrogate markets are available and how they should be evaluated. Why is it that everybody except for the Canadian common drug review can get on board with this?
As I say, our real quarrel is not with Health Canada. We think Health Canada gets it. And we think the progressive licensing framework provides a vehicle by which some of this can actually be done. Unfortunately, when we get to the common drug review, they oftentimes re-review what Health Canada has done; they oftentimes come out with different conclusions. They claim it's because it's real world versus what would happen in a laboratory. We contend that if you don't in fact make the drug available to people in the real world, how will you ever collect real-world evidence? It is being collected elsewhere. We need to be a part of these international collections.
I think there is a little disagreement that the Canadian common drug review is failing Canadian patients. I'll give you an example. Other than rare disorders, 14 innovative therapies were reviewed by the common drug review over the last two and a half years. Of those 14, 12 were turned down. It's the same problem: a lack of long-term sufficient evidence, or it costs too much. Of the two that were actually approved, by their own admission, one was approved with the same lack of evidence, but it cost less than the standard of care, and somebody said, hello, it's okay for you to approve a drug that has not your standard of quality evidence just because it's cheaper.
I think what we want to move towards in this country is a process that's appropriate. We can look at other countries, and I've given you some examples that you can look at when you get the written submission.
There are two things that we want to suggest in terms of fixing the common drug review for rare disorders, and maybe for any innovation therapy.
First of all, there needs to be a separate process. We look at what the Dutch have done; we look at what the U.K. has done. We need to have a separate process that is run by experts who understand rare disorders and will use appropriate processes of evaluation. We do not object to health technology assessments. We don't even object to pharmaco-economic assessment. But it has to be done with the right tools, and it has to be done within the right framework of what we're talking about here. So it has to be a separate process.
The other thing we're suggesting is that there be a separate fund—again, as the Dutch have done, as the U.K. has done in many cases--allocated just for rare disorders. That would help even the playing field, because under the current circumstances, rare disorders can never get access in the same way as more common drugs. We're recommending, based on some of our international experiences and on what's available currently, that 2% of the public drug fund should be allocated separately for rare disorders. It should be handled by a separate committee, by a separate process, and this fund, then, should be established nationally and shared by all the provinces. We would actually like to call upon the federal government to kickstart this by putting together that fund and making it available, and then helping to set the terms of reference and guidelines by which those drugs would be reviewed and accessed.
We don't object to safety and assessment. In fact, patients don't want drugs that are not safe and don't have long-term effectiveness. I think the U.K. has a very innovative program, which we think is very valuable, and that is, when a drug is deemed safe and has sufficient evidence of efficacy, it's made available to patients where there's a high risk in terms of debilitation or death. And the patient then signs an agreement that says, after x amount of time, if you don't get the effectiveness, then you're taken off the drug.
I will just finish by saying that the question was asked to our U.K. visitor, what happens when you take patients off the drug? He says it has never happened. He says the patients take themselves off. Nobody wants to take a drug that isn't working and isn't considered to be safe. We've never had that problem. We would contend to you there's enough good international evidence about how an effective process could be done. We certainly believe, as an aside to it, is that the more appropriate use of HTA should be applied not only to the rare disorders, but also to some of the more common disorders and certainly to innovative therapies.
Thank you.
