Health Committee on May 2nd, 2013

[The Chair, Conservative, Joy Smith]

Let us begin.

I want to welcome everybody here.

We have Mr. David Lee, director of the office of legislative and regulatory modernization at the policy, planning and international affairs directorate, health products and food branch. Wow! Is that ever a long title, Mr. Lee—well deserved.

Also we have by teleconference, from the Canadian Organization for Rare Disorders, Dr. Wong-Rieger, president and chief executive officer. She is joining us from Geneva.

We're very honoured to have you here.

I'm going to begin with Dr. Wong-Rieger.

Doctor, you have 10 minutes for your presentation. Then Mr. Lee will take over from you. Do you understand that, Dr. Wong-Rieger?

[Dr. Durhane Wong-Rieger, President and Chief Executive Officer, Canadian Organization for Rare Disorders]

Yes. Thank you very much. And certainly many thanks for the opportunity to do this by remote teleconference.

[The Chair, Conservative, Joy Smith]

You may begin now. We look forward to hearing from you.

[Dr. Durhane Wong-Rieger]

My understanding is that we are talking about technological innovation and the treatment of rare diseases. I'd like to address a number of types of technologies and innovations that we feel are really revolutionizing the treatments of rare diseases and, certainly, the presence or the availability of these technologies, but also the application of them, especially in Canada. I think there are some things right now that we are doing very well in Canada, some things where the federal role I think has been especially strong, and then there are some ways in which it could be much better.

If we start by looking at the genetic research in terms of identifying the genetic causes of rare diseases, we see that about 80% of rare diseases do in fact have a genetic cause. Canada currently sits as one of the leading countries in doing this type of research. Certainly, I think it stems from the days when we were still identifying the genes that were in the human genome. Canada built up quite a good repertoire in terms of research technology, but also in terms of laboratories.

The challenge, I think, is that we have not been quite as good in terms of using this genetic knowledge to do screening so that we can identify individuals, from newborns all the way through to older adults, who may have these genetic defects, and certainly in terms of using that information in setting in place programs to prevent harm or to deal proactively with the results of those diseases.

Also, I think we can look at the research and development in understanding the causative pathways in these rare diseases. Really, what is the underlying mechanism by which these diseases happen? Again, Canada sits as quite a leader, I think, certainly very recently with some of the research funding that's come through the CIHR and Genome Canada, and then more recently with the funding that's come through with regard to personalized medicine.

I think the challenge again is our ability to use those to, in this case, develop treatments that are based on an understanding of that causative pathway. Canada, I think, has not really invested in the same way and has not made that as much of a priority. I think the challenge, then, is that we may understand how these diseases work, but we don't necessarily move into having the treatments for them.

I think Canada is beginning to.... I think David Lee is going to talk a whole lot about this. It's much to David's credit, as well as to Health Canada's credit, that we are beginning to develop a very good regulatory framework for the evaluation and the ongoing monitoring of drugs, devices, and other genetic therapies, including things like [Inaudible--Editor] therapies in Canada. The challenge we have again is with the application, that is, in making sure that these innovative technologies are really made available to patients in ways that are safe and monitored and, certainly, made available in a consistent way across the country.

Again, I think that where we have begun to do some things around pharmacovigilance post-market surveillance, we are probably not doing anywhere near the kind of job that's necessary, especially when we recognize how challenging many of these therapies are. I think that in many respects there's still a lot of hesitancy in Canada in terms of using the innovation that we in some respects pioneer here and that we have available. Certainly, I think there are a lot of challenges, because we are such a decentralized access environment, and we end up with the provinces and other jurisdictions that are now responsible for making these therapies available, not just from a purchasing and cost point of view, but in the overall management and monitoring of these therapies.

In some respects, this is where I think from a patient perspective we really would like to see some federal leadership. We feel that the federal government and Health Canada can play a huge role, not necessarily in terms of taking over the provision of therapies or the direct monitoring of therapies, but in providing that leadership role, as it has been in some selective cases, and also in providing for the provinces those kinds of guidance, like national guidelines, etc. Again, I think we've heard the provinces ask for this over and over again, so even within a federated environment, we think the federal government itself could play much more of a leadership role and much more of a guidance role.

I think the other thing we are concerned about in terms of some of the innovation coming in is what to do about therapies that are already in place.

I think Canada is probably very far behind other jurisdictions in being able to approve drugs that have previously been used off label but over time are actually indicated, and have demonstrated to be effective, for a rare disease. In Canada we have a very hard time bringing it into the regulatory framework to provide certainly an on-label indication, to provide the safety and guidance for it. So these drugs continue to be used off label in Canada, whereas in other countries they may actually now be part of the regulated and on-label indication.

One of the challenges for this is not only do we not have the good safety and effectiveness information; in many cases the costs are not reimbursed, because they're not considered to be on-label therapies.

Again, Health Canada could in fact take that role. I don't think they're unaware of it; I think this is something that will take a little bit of redoing. It's urgently important when we recognize that about 50% of the drugs that are used by Canadians with rare diseases are actually used off label. That means there's no regulatory oversight, no actual pathway in which they are managed, and a lot of them are haphazardly reimbursed.

Another area where we're playing a leading role right now is in what we call repurposing drugs—taking drugs that are already on the market or already developed and in many cases being able to reuse them for rare diseases, based on some similar pathways and mechanisms. In terms of risks, certainly, because the drugs in some cases have already been approved and are already in use, there should be in fact a much quicker and a less costly way of making those drugs now available for rare diseases.

We would like to see Canada take a deliberate role in that, in part because we are becoming one of the leaders in research on repurposing drugs—again, through the leadership from CIHR, from Genome Canada, and some of our universities and clinics. It behooves us to also then find a way to bring those onto the market quickly and make them available to patients.

That also speaks to extension for the drugs that are already on the market, oftentimes for rare diseases. As we begin to identify other diseases that have similar pathways, is there a way that we can more quickly make sure that these drugs are also going to be available for other patient populations without having to go back to the same level of clinical trials that the drugs in the original indication required?

We're really quite excited by the fact that Canada seems to be getting into the game here. I think we are looking at our regulatory framework and in some respects at possibly being one of the world leaders once it is in fact put into place, and we hope very soon. Quite frankly, I think Health Canada, certainly with the leadership right now, has been taking the best of what's available internationally and incorporating that into what we're doing. They're also looking into the future: where do we believe rare disease drugs, orphan drugs, will be, and what will they be like?

We're very much a leader, as we've said, in the repurposing of drugs, but also in terms of personalized medicines, which are really very close cousins to these orphan drugs, these drugs for rare diseases.

I think that's very exciting for us in terms of where Canada was just a few short years ago in this whole environment of technology and innovation with regard to rare diseases. We're now moving, I think quite rapidly, to taking what is I think recognized by other countries as well as a leadership position.

I think we're positioned very nicely between Europe and the U.S., and I think both jurisdictions look very much to Canada in terms of not only being part of the game, as we say, but also providing some really good bridging information and maybe in some areas also taking a leadership role.

I'll finish by saying that what we still don't have in Canada, to take full advantage of our innovative technology, is a rare disease strategy. In Europe, the European Union has mandated that every country in the European Union should have a rare disease strategy by the year 2014. Every country is moving towards that.

Canada needs to do that, because without that kind of rare disease strategy, we're not going to take full advantage of some of these innovations; certainly we're not going to do it in a consistent way; we're not going to do it in a way that gets, as we're learning, the most effect out of it; and we're certainly not going to be doing it in a cost-effective way.

Some of that would include things like having centres of excellence, where you can designate centres where you have leading researchers and clinicians who can provide not only the information on diagnosis and research and managing clinical trials, but also can serve as a resource to other clinicians and to other sites in terms of these rare diseases.

I think we need some other things that I think only the federal government can do for us well—a national newborn screening program, for instance, and a national disease registry. We cannot have provincial registries when we're talking about diseases in such small numbers. And to make some of these therapies, these technologies available without good registries—

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Wong-Rieger.

I gave you a little extra time. We'll be asking questions of you, as well. Thank you so much for your presentation.

[Dr. Durhane Wong-Rieger]

Thank you.

[The Chair, Conservative, Joy Smith]

Now we'll go to Mr. Lee.

[David Lee, Director, Office of Legislative and Regulatory Modernization, Policy, Planning and International Affairs Directorate, Health Products and Food Branch, Department of Health]

Thank you, Madam Chair.

On October 3, 2012, the Minister of Health announced the development of a modern framework for orphan drugs. These are drugs used to treat rare diseases. This opens the way for increased Canadian research and development of these drugs and for improving Canadian patient access to treatment.

It's a pleasure to appear before the House of Commons health committee to explain more about how this proposed regulatory framework would benefit Canadians affected by rare diseases.

There are dozens of well-known diseases in Canada. They're well known because they affect the lives of many people. There are charities, associations, and support groups for people suffering from those diseases.

But there are thousands of people suffering from other diseases that most of us have never heard of. That’s because they're so rare, they can affect fewer than 12 people in the country. At any given time, even internationally you can have very small numbers of patients.

While some of the rare diseases may affect only a handful of Canadians, in all, hundreds of thousands of Canadians are dealing with these conditions, and they need effective treatments. In Canada it's estimated by some that one out of 12 Canadians is affected by a rare disease.

The diseases are often linked to genetics, as Dr. Wong-Rieger suggested. They can have a very early onset. They can be diagnosed during childhood, often very young. And they're very difficult to study, to treat, and to understand how to regulate because of the small size of the population. It's scientifically difficult to tell how a therapy would work in that population and to pick up safety information.

Rare diseases can be serious chronic conditions—they last throughout the lifespan of the patient. They can be seriously debilitating or life-threatening. They often are life-threatening.

The drugs that demonstrate promise for treating these diseases are often referred to as “orphan drugs”. It's a term that has developed globally, and the United States started that.

Today when a patient with a rare disease needs access to an orphan drug, because we don't have rare-disease regulations currently, it's not available in Canada. The patient’s doctor, often a specialist in that disease, will obtain it through our special access program at Health Canada. But every time the specialist uses this option, he or she has to take time to write out a form to request in writing the allocation of the drug to the patient, and then the department can contact the manufacturer to release the drug to that patient. While this works—and it's what's operating right now—it is time-consuming, and each decision is made on a case-by-case basis. It's an unnecessary burden on the health care system.

Health Canada has also approved some orphan drugs as new drugs under division 8. That's our normal review provision for commonly marketed drugs. While this path has worked in the past as well, it's limited because it was not designed to address the unique challenges of rare diseases. It really doesn't pay attention to the data requirements, for example, that we would tailor in a new framework.

What is needed is a new regulatory framework designed to gather information used to treat small, vulnerable patient populations, specifically tailored to facilitate the development and approval of drugs meant to treat rare diseases, an orphan drug framework.

An orphan drug framework will level the playing field for Canadian rare-disease patients so they, too, can share in the benefits rare-disease patients in the U.S., and in many European countries with such frameworks in place, already have. In those countries and those jurisdictions, they have a lot of experience with rare diseases by now, and they've been very helpful in teaching us about that.

The orphan drug framework will allow Health Canada to approach the approval of these drugs in a flexible manner, recognizing that greater uncertainties may exist for orphan drugs, given the complexities of the diseases and again the small size of the patient population.

First, we're aligning with trusted international counterparts, the European Medicines Agency and the U.S. Food and Drug Administration. And I will say that they're very generous in their advice, opening up what has worked for them and not jurisdictionally. Both have had frameworks in place for orphan drugs for over a decade, and in the case of the States, more than two decades. International alignment of Canada’s regulations will allow our scientists, Canadian scientists, researchers, and regulators, the ability to pool increasingly limited resources to help us to better understand these complex diseases and their treatments.

Second, drawing on the idea of life-cycle management, the framework will also allow us, the regulator, to more closely follow the safety and effectiveness of these drugs once they're brought into the market. This will be done by ongoing post-market data collection relating to the drug’s safety and efficacy or effectiveness. This innovative approach complements the current pre-market focus with a more balanced, dynamic, and fluid set of regulatory interventions, and it will better serve the patients’ needs while maintaining a strong safety oversight.

We want to make sure the design of our approach is very patient-centred. The patient's voice needs to enter into that regulatory process, so we want to enable patients to have a voice throughout the decision-making.

Because the proposed regulations will align with international frameworks, which is very important, it will be more commercially feasible for pharmaceutical companies to develop and then bring their drugs to market in Canada. This is because the international alignment gives drug manufacturers a more predictable, operationally less burdensome path to follow. What they follow in other jurisdictions will be typically sufficient here as well.

A more predictable regulatory path, with clear research requirements and flexibilities to enable international collaboration, also creates space in which Canadian research and innovation can thrive, and we're trying to pay attention to this in designing the framework. The framework will also provide for greater transparency to improve the gathering and sharing of information among patients, health care professionals, researchers, payers, and international regulatory partners.

Improved transparency is expected to result in more informed, evidence-based decision-making. It also brings with it increased public confidence in evidence-based research and the safety of research participants. This is because the broad sharing of research data accelerates the research, fosters data integrity, and increases accountability.

Most of all, the new framework will benefit Canadian patients with rare diseases by improving access to new and existing drug therapies that might have been harder to get or not available at all without these new rules.

As part of our work to better understand the impact that the orphan drug framework will have on Canadians, Health Canada has also met with many Canadian researchers, clinicians, rare disease representatives, and patients. I've done this often in conjunction with CIHR and other valuable domestic colleagues.

In response to what we heard, Health Canada, with support from the Canadian Institutes of Health Research, has launched Orphanet. There's been a lot of effort around that. It's a very important online resource, a global resource that offers a directory of specialized information for people with rare diseases and health care service providers. It includes information about specialized clinics, medical laboratories, clinical trials, and registries. Together the new framework for orphan drugs and Orphanet will create a better environment to increase access to information for patients with rare diseases and the new treatments coming onto the market.

In closing, the proposed framework is in the final design stages. We will soon be broadly targeting public consultation. Comments and feedback would then be gathered during consultation and incorporated into a final version of the proposal.

Thank you for inviting me to appear today.

[The Chair, Conservative, Joy Smith]

Thank you for being here.

Now we'll go into our seven-minute Q and A round.

We will begin with Ms. Davies.

[Libby Davies, NDP, Vancouver East, BC]

Thank you very much to both our witnesses for being here today, particularly to Dr. Wong-Rieger in Geneva. I guess it's quite late there, right?

[Dr. Durhane Wong-Rieger]

Yes, it is.

[Libby Davies, NDP, Vancouver East, BC]

Thank you for being up late to be with us here, where it's still a sunny afternoon in Ottawa.

I realize that today we're dealing with a very specific issue, which is rare diseases, but nevertheless it does relate to bigger issues around innovation as well. I'm certainly no expert. Probably none of us is an expert on rare diseases, so the information that was provided today was helpful in understanding that a lot of people are affected by rare diseases in aggregate in our country.

I want to focus a little on looking at the new framework that's coming. I notice you didn't speak about the issue of drug safety. This is something that's currently very much before us. We've had a number of examples recently with drugs. We have one today whereby there's now a warning from Health Canada after we heard from the Americans about a month ago. This is a huge issue. I want to know if I'm correct that with some of these rare diseases, so many of the drugs are off label, as Dr. Wong-Rieger has said. I don't know all the ins and outs of that, but it sounds as if it's not a great regime and that it's much better to have things on label and within a regulatory sense.

For many of these drugs there could be increased problems in terms of adverse side effects, drug safety, and so on. Am I correct that there would be a higher incidence than in other “mainstream” diseases? I don't know what to call them.

[The Chair, Conservative, Joy Smith]

Mr. Lee.

[David Lee]

Thank you, Madam Chair.

In terms of safety, that's a very, very important aspect of the new rare disease framework. Recognizing that the food and drug regulations themselves are somewhat older, we do have powers on market tracing and finding out what's going in the market, largely through the reporting of adverse drug reactions. That also happens through delivery and special access. The manufacturer and the physician would have to report back in if there's an incident through that transaction. So if the orphan drug is going out into the market on a one-by-one request, we do see it. The problem is that you don't get a population view of what's going on. The new framework would be much more deliberate. Safety would be a matter of trying to look out and understand what it is you need to follow if you've got any particular concern. If you start to detect something, you can put in further tests and studies and make sure you really follow what's going on with the drug, including utilization studies. So you can follow if it's being used outside of the labelled indication, which means that physicians are prescribing it, notwithstanding that it hasn't been completely demonstrated with us.

Basically, it would be a much more advanced way to follow out safety issues. That's not to say that pre-market there's any less of a look. We really want to make sure that as the drug—

[Libby Davies, NDP, Vancouver East, BC]

Is there actually going to be post-market surveillance for safety based on this framework? Is that included in the framework?

[David Lee]

That would very much be included.

[Libby Davies, NDP, Vancouver East, BC]

Okay, thank you. I didn't actually see it spelled out in the brief in those terms. It was sort of alluded to, maybe, if you stretch it.

But it is clearly going to be part of that?

[David Lee]

It is very clearly. When we talk about life-cycle management, that really does get to the crux of following the drug, both from a safety point of view and also a benefit point of view.

We start monitoring right from the first introduction in human beings, so the first phases of clinical trial we're starting to already plan out how we will construct vigilance. That's the new scheme. The old scheme is a little bit more passive: you wait for something to happen and it gets reported.

[Libby Davies, NDP, Vancouver East, BC]

Why has it taken so long? We hear that in the U.S. they've had such a program for 10 years. I just wonder why is Canada so far behind on this.

[David Lee]

We're learning from the U.S. proposals. Functionally, within Health Canada, we also get the benefit of a lot of the tools that have been constructed by the U.S., for example, the REMS—so the plans going out into market to follow vigilance. We do get those filed. We also get them filed from Europe. There's been a convention that we've been part of through the International Conference on Harmonization on pharmacovigilance for Health Canada. We've implemented much of that. The thing is to follow in with the regulatory proposals. That's what this would do in the orphan drug setting. It would put in an ability to require a plan to go out into the market and follow the safety issues as a part of your licence. So the company would be obligated by law to make sure that they are tracing out and actively looking for signals where we need to.

[Libby Davies, NDP, Vancouver East, BC]

I have one other quick question.

We're studying innovation. I would imagine that one innovation in this issue is affordability.

Can you give us an idea, and maybe Dr. Wong-Rieger could give us an idea as well, of the costs of some of these drugs? Are they incredibly expensive? I just think about the commitments that were made in the health accords to have drug coverage, particularly in situations where people are paying astronomical prices. Can either of you give us a sense of what some of the costs are?

[The Chair, Conservative, Joy Smith]

You have a minute left.

[Dr. Durhane Wong-Rieger]

Overall, I think what we do recognize is that many of these drugs, because they are being developed for very small patient populations, can come in at a very high individual cost—though it's not true for all of them. I will give you a bit of a reality check. If we think about all the drugs that are now currently being funded for rare diseases, including some that you've heard about as being very expensive, the cost still amounts to only 0.7% of the public drug budget because the numbers are very small. A very good projection that was recently made by researchers in Europe, where there's much better drug coverage for these rare disease drugs than we have here in Canada, is that because of the rates of development, the numbers involved, and the fact that when you develop a drug for one of these rare diseases many of the patients come on right away—so it's not likely you're going to get a continuing increase in these patients—at most it would never be more than between 3% and 6% of the total. That was their estimate.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Wong-Rieger.

Now we'll go to Dr. Carrie.

[Colin Carrie, Conservative, Oshawa, ON]

Thank you very much, Madam Chair.

Thank you to the witnesses for very interesting presentations.

I just want to follow up along with my colleague. We are doing technological innovation, and I think one of the innovations is actually data collection, data availability, and international cooperation. When I've talked to stakeholders, it seems, as Mr. Lee pointed out, that sometimes there are only maybe 12 people in Canada with a certain disease, so how do you study it? How do you bring this about?

Mr. Lee, you mentioned this online technological innovation, Orphanet Canada. I wonder if you could elaborate a bit more about exactly what that is, and if it could be modelled for other things? Is this online resource something that patients can load data into? Is it something that researchers can take something out of? Or is it something else? Could you elaborate a bit more for us?