The first of many promises Bruno Mäder, head of the company’s biosimilars business unit
The month of October saw a new Canadian alliance of drug manufacturers – the Canadian Biosimilars Forum–issuing a challenge to both policy makers and health system leaders in Canada to embrace “the opportunity that biosimilars represent to both patients and to Canadian health care.” Members of the forum contend that biosimilars can play a significant role in the Canadian health care system once the market exclusivity of the originator product has ended.
Merck Canada Inc. is one of eight partnering companies that are taking part in this initiative. The company in partnership with Samsung Bioepis had previously announced in December, 2015 that it was preparing to bring to market a diversified portfolio of biosimilar medicines in Canada over the coming years. Well, the first biosimilar from Merck has arrived, in the form of a biosimilar/ subsequent entry biologic for Enbrel® (etanercept), also known as SB4. The product received regulatory approval in Canada for the treatment of rheumatoid arthritis and ankylosing spondylitis and is the first version Amgen’s Enbrel to be approved in Canada.
This month we go one-on-one with Bruno Mäder, head of the Merck Biosimilars Business Unit in Canada, to discuss the significance of this first approval, and how the broader preferential listing of biosimilars (which according to Mäder are on average 20 to 30 per cent cheaper than biologics) can help sustain the future of Canada’s healthcare system. He also believes that BRENZYS™ is set to allow Merck to help generate savings for Canadian provinces, and contribute to the sustainability of the healthcare system, while offering a better value treatment option to the 300,000 Canadians suffering from rheumatoid arthritis and ankylosing spondylitis.
Q: My understanding is that a biosimilar can have some variations to the originator, as long it produces the same results. Can you tell us a bit about your biosimilar, and how it stacks up against its originator Enbrel®?
Brenzys™ is a biosimilar of Enbrel®, a drug that’s been approved for more than 15 years and which was the first anti-tumour necrosis factor (anti-TNF) agent approved in Canada. Brenzys™ has been approved for two indications, one is rheumatoid arthritis and the other is reducing symptoms of ankylosing spondylitis. The approval of Brenzys™ is supported by rigorous analytical structural and functional testing, as well as a Phase 1 pharmacokinetics study and a Phase 3 clinical study comparing Brenzys™ to the originator biologic.
In terms of efficacy, including endpoint such as ACR response, and safety profiles, both were similar to the originator, Enbrel®. One difference that was reported in the Phase 3 study, and this may in fact be beneficial for the patient, is related to one of the side effects of using anti-TNF agents. When you inject the drug, there are a portion of patients that can have what are called injection site reactions. In our case, we were actually able to show fewer injection site reactions than the originator Enbrel®.
Q: How are the two drugs structurally different?
I think what’s really important is the totality of evidence and that the Phase 3 trial showed that the drug actually works the same way as the originator. In order to be approved, biosimilars must demonstrate similarity to the originator. This means that while not identical, any difference in quality attributes should have no adverse impact upon safety and efficacy of the biosimilar. As I mentioned, on the safety side they were very similar; this is not surprising as they have the same primary amino acid sequence as its reference product.
As well, there are differences which may be due to newer manufacturing technologies. We’re essentially manufacturing this biosimilar with more recent technologies, whereas the older biologics were launched in the mid-90s, early 2000s, using technology from that era. There are definitely improvements in how we manufacture these products and that’s one of the reasons why we’re able to offer cost-savings. Whatever differences there might be, they have not been shown to have any impact on efficacy or safety, and that’s what matters to the patients and their physicians.
Q: Where does it get injected?
As outlined in our patient information pamphlet, there are different areas on the body where it can be injected, for example, the abdomen or in the thigh, either with an auto-injector or a prefilled syringe. In Canada, approximately 90 per cent of all patients will use the auto-injector. The auto-injector is a bit different than the Enbrel® one, in that it doesn’t have any buttons to push which can sometimes be a problem for patients who suffer from arthritis, and it is also latex-free. You literally just push the tip on the skin area where you’re injecting and the drug injects itself automatically. It’s a very user-friendly patient device.
Q: Are there differences in product development when it comes to biosimilars vs originator biologics or other drugs?
When you’re doing research to discover a new drug, imagine an inverted pyramid model where the base of the pyramid or the largest area really has to do with clinical trials. Essentially, you have a hunch that a drug will work for a certain indication, so you have to perform several trials to demonstrate that it works. With biosimilars, it’s like a normal pyramid where most of your time is actually focused on characterizing the molecule that you’ve developed to prove that it is similar to the molecule that is already on the market, and only a small part of the pyramid is the clinical trial part, where you confirm your preclinical work.
In other words, we didn’t have to do several trials to get the biosimilar approved, but we had to do at least one major trial and several preclinical tests, which differentiates the biosimilar market from say the generic market, where no clinical trials are required, only a bioequivalence study is necessary.
Q: In terms of healthcare savings, generics have reshaped the small molecule market. The Merck stance in Canada is that Biosimilars can reshape the biologics market in the same way. Can you elaborate on this statement using Brenzys™ as a prime example?
For us (Merck), we’re an innovation company. It’s our 125th anniversary this year and innovation is still at the core of what we do. We believe that biosimilars themselves offer a form of innovation, and with Brenzys™ specifically,
we have innovated with a button-free auto-injector which does not contain latex. Our partner, Samsung Bioepis, has also worked on the manufacturing side to reduce costs which allows us to offer a better price. Biosimilars offer Canadians a lower cost alternative without any compromises on safety and efficacy. The savings could also allow payers to fund access to new innovations for patients.
Q: In Merck’s press release announcing the approval of Brenzys™, you talk about preferential listings for biosimilars. What is meant by preferential listing for biosimilars, and who hasn’t provided it and why?
Preferential listing has been given to Inflectra™ which is a biosimilar of Remicade®; we hope the same will happen for Brenzys™. It essentially means a payor has mandated the use of a certain product before another, either for clinical or pure cost reasons. In the end, it’s about putting patients first, that’s certainly the motto for Merck, there shouldn’t be any compromises on efficacy and safety, and I think with Brenzys™, we’ve shown that our product is as
efficacious and as safe as the originator product. Once you’ve passed that first step which is most important, then it comes down to what is most affordable. The provinces that have chosen the path of a preferential listing are no longer going with a simple lowest cost alternative policy; they’re essentially mandating a certain brand or DIN number to be prescribed instead of the originator brand. Québec and Saskatchewan are the two provinces that have so far not opted for a preferential listing policy. Québec has applied its standard approach of the “le prix plus bas” or the lowest price that they will pay, which works well for small molecule generics but clearly is not working for the biologic market.
For example if the biosimilar is $800, the original is $1,000, the Québec government will now only pay $800, but that doesn’t mean the patient is going to go on the biosimilar. He/she may choose to actually pay the difference in price, or in some cases we’re seeing the originator companies actually offering to pay the difference via their patient support programs without lowering their list price. By having a preferential type listing, payors are stating they will only reimburse the biosimilar with the DIN # XYZ. Let’s be clear, we’re not necessarily saying that we want governments to prefer Merck biosimilars, what we are suggesting is that it would be beneficial for payors to mandate use of biosimilars before the originator product when it’s available.
The last couple of months have been very encouraging if we look at what has happened to the first biosimilar of Remicade® called Inflectra™. All provinces except Québec and Saskatchewan have now preferentially listed Inflectra™ (the biosimilar) over its originator (Remicade®). We’re also not seeing many private payers adopting a preferential policy. It’s unfortunate, by making the market unattractive to biosimilar manufacturers; payers will lose the opportunity for significant savings in the long run
Q: Disruptive technologies in any form have to overcome several hurdles, whether it’s an education component, making people familiar with how they work, and even why they are a valid cost option. How have both private drug plans and Health Canada viewed biosimilars, and what are some of the challenges that you have faced getting a product such as Brenzys™ on their radar?
It’s been an interesting journey the last 18 months. I think Merck has done a lot of work to maybe correct certain facts about biosimilars that weren’t depicted completely or accurately in the market. It’s been a multi-stakeholder
type of journey, patient groups are very involved in this market and they are obviously very concerned about patient well-being. We’ve done a lot of work to try and educate them, and we tried to do the same thing with payors. Considering that Canada is still a relatively young biosimilar market, I think the recent decisions by most provincial payors to list Inflectra™ preferentially is a very good sign. It only applies to new patients for now, with no decisions being made on existing patients yet, but it’s still a move in the right direction.
The next big step is what will they do for existing patients, that’s where there is a major and quick cost saving opportunity. In Europe, biosimilars have been around for approximately 10 years and there’s dozens of them out there, so Europe is a bit more used to it. The data is accumulating and we are seeing some countries in Europe completely transitioning patients from the originator to the biosimilar. Things seem to be going very well and they’re generating major savings.
The private side in Canada represents approximately 50 per cent of the patients. There is tremendous potential there for third-party payors to offer companies and their employees the chance to save money on their health plans. So far, less than 10 per cent have opted for preferential listings, most are adopting a more conservative position and simply listed the biosimilar while still allowing patients to initiate therapy on the originator. Some payors have made private agreements with the originator by leveraging the lower list price of the biosimilar. While this will generate savings, it will no doubt limit the penetration of biosimilars in the private market and potentially discourage biosimilar manufacturers to enter the Canadian market.
Will the recent preferential listings by most provinces encourage private payers to be more aggressive on biosimilars? Perhaps, time will tell. Certainly great strides have been made but a lot can still be done to ensure Canadians will take advantage of the biosimilar era. If you look at the next five or six years, and you start attributing 20 to 30 per cent discounts on all biologics that will lose their exclusivity, you could generate up to $8 billion to $9 billion in savings. That’s a lot of money for payers to fund access to innovative therapies that many patients need.
Q: What are the strongest concerns you’ve heard about biosimilars?
I think there was a lot of concern around safety for these products. First and foremost for Merck, and I know for all involved in this market, the health of the patient is most important, nothing should be done that would compromise that. When you are facing the potential of having to switch drugs, from a biologic to a biosimilar, it’s a big concern for patients because obviously they don’t want to move away from something that is working for them. At the same time, when it comes to new patients the data is very clear, there’s no difference in terms of efficacy and safety and for patients who did make the transition from the originator to the biosimilar, preliminary results showed that they continued to do well. That being said and based on a trial, we believe that patients who initiate or switch to Brenzys™ will continue to do well, or at least as well as they were doing on the originator product.
Q: I expect that the level of expertise to research, manufacture and develop these types of compounds needs to be high. Why did Merck choose Samsung Bioepis Co. over other potential partners?
Samsung is an iconic company that most people associate with electronics, but they are actually quite involved in health care, with some of the major hospitals in Korea actually belonging to them. We like their capabilities to develop and manufacture high quality biosimilars and when we look at the speed in which they were able to develop Brenzys™, I think they’ve done a phenomenal job. They are currently expanding their capacity in terms of biosimilar production, and I believe that they want to become the top biosimilar manufacturer in the world. We feel very good about the partner we are working with.
Q: A question you’ve probably heard before, but as a company that develops originator biologics as well, why get into this area when it could have a negative impact on your earnings down the line?
We understand that at times, biosimilar approvals won’t work in our favour because there will be biosimilars for Merck originator products as well. At the same time, as an innovator company, we understand that the market or the payors- society in general – needs to find a way to fund new innovations and once there is loss of exclusivity on an originator molecule, we believe there’s a place for biosimilars just like there is a place for generics. We’re being very transparent about that. I think that some payors are finding it our approach interesting, maybe even refreshing. We’re an originator company, R&D and drug discovery is still our foundation.
In the case of Brenzys™, while the etanercept molecule is not new, I think we made efforts to try and improve it such as the device to administer it. We understand that some of our own biologics will lose exclusivity, and companies will have a biosimilar of our product. That’s never a pleasant day for an originator company, but it does push you to find new ways to innovate. We recognize that it’s impossible for the healthcare system to continue to pay full price for biologics that have lost exclusivity and then to find money to pay for new innovations. There’s a time to support originator molecules when they’re patented, to help us recoup our investment costs and generate a profit, but there’s also a time where government and payors need to find ways to save money and hopefully reinvest those savings in innovations that our company and others will bring to the market. That’s how the healthcare ecosystem will continue to function.
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