Sonja Quale, PharmD, chief clinical officer and vice president of informatics, Confidio, recently spoke about the many challenges biosimilars face coming to market and where the market might be heading. Part 1 of this interview with Scott Vogel, partner and PBM executive of Confidio, can be found here.
Can you please tell us about yourself?
My name is Sonja Quale. I graduated with my doctorate in pharmacy from the University of Minnesota. I’m currently the chief clinical officer and vice president of informatics at Confidio, a technology-enabled pharmacy consulting firm. I lead their clinical strategy, clinical product development, and oversee analytics and reporting.
Prior to Confidio, I spent 17 years in the pharmacy benefit management (PBM) industry at Express Scripts, both in a clinical and an analytics capacity. Prior to Express Scripts, I was the chief clinical officer at PharMerica, a long term care pharmacy services organization.
Can you explain the key differences between biologics, biosimilars, reference generic, and interchangeable products?
The first thing that we need to do is define what a biologic is, because they are different than what you would consider a traditional oral solid, a tablet or capsule. A biologic is very large, complex molecule that is manufactured using biotechnology. The process is complex. For example, a typical protein drug may include in excess of 5000 critical process steps, many times greater than small molecule manufacturing. Not only that, but they’re not synthesized through a chemical process like the oral solids. Biologics have to be manufactured in living cells, which is where the term biologic originated.
A reference biologic is the original biologic that’s approved by the FDA and out on the market. A lot of people call biologics generics and that is not really a true statement.
A generic is an exact chemical replica compared to the brand. Its manufacturing process is very straightforward. Generics have to match exactly in chemical structure to the brand product. Generics are different in that they have to be exactly the same, whereas the biologics have to be highly similar.
Because of this complexity in replicating a biologic drug, it has taken a long time for competition to grow in the market. Additionally, there wasn’t a pathway for approval other than through the traditional approval process, and as a result for a long time, there was no competition for biologics. With the passing of the Affordable Care Act, the Biologics Price Competition and Innovation Act (BPCI) was enacted. This created a pathway for biosimilar manufacturers to gain access to the reference product in order for them to be able to replicate as close as possible the actual biologic, which they could then submit to the FDA for approval.
A biosimilar only has to be highly similar in structure and function to the reference biologic, not necessarily perfectly exact. There might be a non-clinically active part of a molecule that creates a difference such as a buffer or stabilizer. That is okay, it just has to meet the standard of being highly similar. Additionally, they have to have equal safety to the reference product.
Biosimilars have to be evaluated and compared to that reference product both structurally and clinically. There can be no clinically meaningful differences from the reference product in both efficacy, safety, purity, and potency. This is basically the criteria, which includes toxicity as well. Though they do not have to do a full-blown clinical trial to prove that the biologic works for the disease, enough evidence has to be submitted to prove those five areas.
What are some of the most significant barriers biosimilars face coming to market?
I’d put it into three different buckets; knowledge, interchangability, and formulary status. Knowledge is a barrier in both awareness of what bioimilars are and whether they are available. This is in the physician community, as well as the patient community.
Interchangeability is a barrier, as far as I’m concerned, in terms of adoption rates. Without the ability for a pharmacist to automatically dispense the biosimilar without a new prescription, the biosimilar utilization will remain low. This will also be viewed by manufacturers thinking of bringing a biosimilar to market as a disincentive, however, if guidance on interchangability is finalized, hopefully the manufacturers will pursue this status and we will see higher adoption rates.
The biggest barrier is formulary status. Manufacturers offset the cost of the originator biologic with rebates in exchange for preference on a formulary, which basically creates a disincentive for a PBM to promote the biosimilar. Formulary status of the reference biologic seems to be the biggest determinant of how prevalent the use of the biosimilar is going to be. There’s a correlation between uptick in utilization of the biosimilar and whether any of the big PBMs have them on formulary.
How does the Biosimilar Action Plan from the FDA help or hinder the innovation and inclusion of biosimilars?
For the most part, it will be a good thing. For me, the biggest win, if it comes to fruition, is the potential ability to use data from other countries.
There’s so much higher use and therefore knowledge of these products, in Europe, for example, that the biosimilar manufacturer should be able to use that clinical data in order to bring their product to market in the United States. To me, that’s the biggest win in that as it reduces the cost for the biosimilar company. This should speed approval process and reduce a barrier to entry due to cost for these companies.
Going back to one of the barriers to entry for biosimilars, knowledge of what biosimilars are, how they are approved etc. The education component of the BPA and trying to improve the awareness and the knowledge in the market on the safety, efficacy and availability of a biosimilar so that it becomes basically the first thing that the prescribe as opposed to something that they rely on the insurance to determine.
Where there is risk, is if the FDA cannot prevent the gaming and attempts of manufacturers to delay competition. If this continues, we may see biosimilar companies decline to bring a product to market because it isn’t a financially viable option.
Can you highlight some of the most recently approved biosimilars and what is making them more successful than others?
Most recently approved products have been in the areas of cancer, with biosimilars for Herceptin (Ogviri, Kanjinti (launched 7/18/2019) & Ontruzant), Rituxan (Truxima), and Avastin (Mvasi – launched 7/18/2019), blood disorders with biosimilars to Neulasta (launched 1/3/2019) and inflammatory disorders with options for Enbrel (Erelzi), and Humira (Hyrimoz). Some of these products have not launched to the market yet, primarily due to patent litigations.
In terms of cost effectiveness, what can payers and providers expect for products like biosimilars as more begin to come to market?
Typically, right now, we’re seeing 20% to 30% gross cost savings with a biosimilar, compared to the reference biologic. I don’t anticipate that that’s going to change, especially if the Biosimilar Action Plan breaks down some of the barriers with respect to the approval process.
If that approval process becomes easier and faster, then clearly there’s more incentive for them to bring it to market. We’ll continue to see the 20 to 30 percent savings.
How do these products compare in terms of improving patient care and outcomes?
From a clinical perspective and from a clinical outcomes perspective, there shouldn’t really be any difference. This is really all about cost, in my opinion. The biggest challenge with what is happening with the favoring of the reference biologic is that it doesn’t benefit the patient in that case. Typically, they don’t see the value of the rebate.
The manufacturer might be giving the health plan or the PBM the savings or the rebate associated with it, which offsets the additional cost of the biologic compared to the biosimilar. Essentially, let’s just say that they end up being cost neutral.
Unfortunately, the patient is the one that has to, especially with these high deductible benefits that the patient typically has, they end bearing the brunt of the cost. They don’t see the value of the rebate that the payer is actually getting on the back end. That, to me, is the biggest unfortunate challenge within the cost side of things.
Can you describe some of the top features of the July 2018 Biosimilar Action Plan? What do you believe is the most important?
There are four key features to the BAP: One, improving efficiency in the approval process which should decrease costs and improve speed to approval. Two, improving scientific and regulatory clarity for biosimilar manufacturers, including more information about the reference biologic and potentially allows foreign use data, all of which will hopefully lead to more interchangeable products. Three, Increased education and improved understanding of biosimilars amongst clinicians, payers and patients, thus increasing utilization. And four, supporting market competition, reducing gaming of FDA requirements and other attempts to delay competition.
Is there anything that you’d like to add?
The only other thing I could add would be just the fact that we really need to keep a good eye on what the pharma companies are doing in terms of basically preventing the biosimilars coming to market.
I mentioned briefly that one of the big barriers to market are the pharma companies. Not only is it on the rebate side and preventing those from being on formulary, but to essentially fight patent—it’s the whole patent infringement.
They’re always going to be looking for new uses of their product, which will delay the ability for biosimilar to get all of the indications at the same time and things like that. To me, it’s such a complex manipulation that takes place, in my opinion, to try and prevent getting these good drugs and inexpensive drugs to market.
Of course, pharma has deeper pockets trying to prevent that versus these biosimilars. My biggest fear is that it is going to disincentive somebody from actually jumping into the biologic and biosimilar manufacturing space because they might not see that it’s going to be too high of a hurdle for them to actually get that drug market. I hope that doesn’t happen, but that’s probably my biggest fear.