IPD Analytics Experts Discuss the Insulin Pipeline

CfB: Hello, I'm Matthew Gavidia. Today on MJH Life Sciences News Network, The Center for Biosimilars® is pleased to welcome Dr Leslie Fish, vice president of Clinical Pharmacy for IPD Analytics, and Jeffrey Casberg, vice president of Clinical Pharmacy for IPD Analytics. Can you both introduce yourselves and tell us a little bit about your work?

Casberg: Sure, Jeff Casberg, again, one of the vice presidents of clinical pharmacy at IPD. We service many different constituents in the pharmaceutical landscape: payers, pharma manufacturers, specialty pharmacies, retail pharmacies, etc. I work with these manufacturers and payers to help them interpret formulary management and other aspects of the pharmaceutical landscape such as [what] we're speaking to today on biosimilars.

Fish: Hi, I'm Leslie Fish and I do the same thing that Jeff does. We each take different areas and one of the areas that I actually work with is oncology.

CfB: So, going to the first question, Leslie, can you please tell us about the biosimilars that have been launched already in 2020 and the launches you anticipate for the remainder of the year?

Fish: Sure. I'm going to divide these into 2 questions. And I'm first going to talk about what we're seeing right now currently with biosimilars and then I can actually take question 2, which is, what are we going to be seeing for the rest of the year and what should it look like? So, first of all, on the market, as far as biosimilars for oncology, we have Herceptin [trastuzumab], Avastin [bevacizumab], Rituxan [rituximab], Neulasta [pegfilgrastim], and Neupogen [filgrastim]. Historically, we've seen very slow trends and utilization with the current biosimilar medications we have. However, looking at some of the utilization data for the first 3 months in 2020, for instance, in the United States, the trend does look like it's increasing at a higher rate. When we look at the combined use in the biosimilar against Herceptin, Avastin, and Rituxan, they represent almost 42% of the market. So, that's a much higher rate of increase than we expected based on what had been occurring over the last few years with the biosimilars that are already on the market. Again, we have not reached the European community rates, but it is increasing in the right direction. Some of the questions we're asking for and looking for answers include, will the biosimilars look more like generics in that once there are more products available, will the price drop more? So, as we all know, as the number of generics increase, the price can drop dramatically. Unfortunately, we don't have historical data yet on the biosimilars to show that this will occur. Another question that we have to ask is will the cost come down as more products come onto the market or will it come more from the rebate and contracting side? We do expect to see this with both the biosimilar agents as well as the branded products. Another question we ask [regards] specialist prescribing of biosimilar agents. Will they prescribe them for all the biosimilars, even the biosimilars that do not have the indications that the [reference] product has? We're beginning to see that oncologists are willing to do so, understanding that the reason for the lack of indications is a legal one and not a clinical one. And finally, we actually have to see if there's going to be movement from products that have biosimilar agents, again, Herceptin, Rituxan, and Avastin, to products that actually don't have available biosimilars. What is an example of this is Herceptin to Herceptin Hylecta [trastuzumab and hyaluronidase-oysk], or to Kadcyla (ado-trastuzumab emtansine), or if the combination trastuzumab-pertuzumab [Perjeta] subcutaneous version is approved, would the Herceptin and biosimilar Herceptin be moved to those products?

CfB: So, Leslie, just to build off that, we have not seen any biosimilar approvals so far in 2020. So, are you anticipating any FDA biosimilar approvals this year?

Fish: Again, I'm speaking for the oncology [products] and the answer is yes. First of all, there could be 2 pegfilgrastim products approved this year. One of them is HSP-130 (pegylated filgrastim) by Hospira, and Rolontis (eflapegrastim) just by Hanmi. If these are approved, they're going to be joining Neulasta, Neulasta Onpro, Udenyca (pegfilgrastim-cbqv), Fulphila (pegfilgrastim-jmdb) and Cyltezo (adalimumab-adbm). This would increase the number of biosimilar pegfilgrastim [products] from 3 to 5, and that's counting Neulasta and Neulasta Onpro separately. There could be 2 more bevacizumab biosimilar products: 1 of them is SB8 by Samsung Bioepis, and the other is Bmab-100 by Biocon. That would bring the number of Avastin biosimilars to 4. We could also see 1 more rituximab product, and that would bring the number of biosimilar rituximabs to 3. And finally, we can see 1 more [biosimilar to the ] Herceptin trastuzumab, product come to market, bringing the total number of biosimilars for Herceptin to 6. So, with this number of biosimilar products, we do expect to see lower costs.

CfB: Please tell us how and why COVID-19 is affecting the pace of biosimilar development and what implications this might have.

Fish: So, yes, we can definitely see a slowdown in the approval of medications. This may not be with medications that are near approval, however, products that are not near approval, that are a little bit farther out, and definitely those that are being developed, we could see a slowdown. I'm just going to give you a few reasons; there's really many more, but I'm just going to give you a few reasons for this. So, number 1, we can receive a delay or postponement of the FDA advisory committee meetings. We've already been seeing that. There can be an inability for patient recruitment. There's an inability for patients to actually see the physicians, which means that the patients are not getting follow-up testing. Also, the drug manufacturers themselves are postponing clinical trials to work on COVID-19 therapies. They actually took scientists and their investigators off projects and put them on the COVID-19 therapies. Finally, and again, this could begin to delay some of the medications coming to approval, the FDA has postponed inspecting the manufacturing facilities. Again, I just want to reiterate, these are only some of the reasons that we could see slowdowns and approvals during the pandemic.

CfB: So, Jeff, March 23 was an important day for insulin and growth hormone products. Can you explain this regulatory change and its significance? Do you anticipate that manufacturers will be more motivated under the biologics pathway to develop these products, particularly insulin?

Casberg: Sure. Just to start from the beginning, many years ago, when there were biologic products to be approved, there was not a biologic pathway. So, there was only new drug applications (NDAs), there wasn't the BLA (Biologics License Application) pathway that there is today. These products were required to be approved, they were approved as NBAs and that took place for a number of years. Then, the FDA developed this BLA pathway for biologics. For a number of years now, there's been a group of products that are actually biologics, but not approved in the BLA pathway. So, the FDA had planned for this conversion—which took place in March 2020—for quite a while. Now, the conversion took place and it was with a number of products, a number of classes of drugs--about 88 drugs and 15 classes, or so. You might say, "OK, what's the big deal about this NDA to BLA conversion." The key is that prior to the conversion, the chance of interchangeability for these products on the NDA pathway was unlikely. There wasn't a clear way for the FDA to approve a generic biologic. There wasn't such a thing. Now with the conversion, these products are biologics, and they can have biosimilars, and then they can apply for interchangeability. So, this conversion in March of 2020 kind of opened the door for a whole new group of biologics and the opportunity for these products to have interchangeability in the future. At the present time, payers, patients, and pharmacies won't really see a difference. When they'll see this impacting is once 1 of these groups of products, the biggest being insulins and growth hormones, if 1 of those products becomes or receives the interchangeable designation from the FDA, then at that point, there could be interchangeability and increased competition. The second part of your question was about was there going to be more motivation for the manufacturers to develop products here? I would say absolutely. It opens up a whole new group of products for these biosimilar manufacturers to create revenue for their companies. The biggest categories, I mentioned insulins, growth hormones, and also infertility medications, pancreatic enzymes, and [products to treat] Gaucher disease. So, yes, we think that there's going to be more activity in these particular therapeutic categories.

CfB: You touched on it briefly, but do you see any evidence that insulins are already on the move?

Casberg: Yeah, there's been quite a bit of movement already. I'll break it down into 2 different areas, the long-acting insulins, and the shorter, fast-acting insulins. First, on the long-acting side, the majority of activity we've seen to date is with Lantus (insulin glargine). In 2016, Basaglar (insulin glargine) was approved by Eli Lilly. It's been pretty successful. It hasn't been a biologic and hasn't been interchangeable, but based on being a glargine molecule, many of the payers have adopted it in their formularies and it's picked up quite a bit of market share. Coming down the pathway for future approvals, Mylan has a product called Semglee (insulin glargine), approvable in the middle of 2020. Sandoz has a product that we think is going to call Basalin, approvable late 2020, early 2021, or so. More recently, we saw some news on a manufacturer called Lannett also developing a long-acting Lantus. There's also a bigger product in the long-acting side called Levemir (insulin detemir). It's a multibillion-dollar product, but, very interestingly, we have not seen a lot of biosimilar attempts by manufacturers to copy Levemir. So, we see continued activity on the Lantus side, but not so much on the Levemir side. Other impacts of this change, we see that there's also opportunity that these copies of Lantus could impact some brands, such as Novo Nordisk's Tresiba (insulin degludec) or Sanofi's Toujeo (insulin glargine). So, these could affect these branded companies. Ultimately, another impact we can see is that manufacturers, such as Novo Nordisk and Sanofi, could issue what are called authorized biologics. At least, that's what IPD is calling them. On the generic side, we have authorized generics, but we think that with all this competition on the long-acting insulin side, there could be authorized biologics. So, Novo Nordisk could come out with an authorized biologic Tresiba, reduce the price, reduce the out-of-pocket costs to customers, and better compete with that. On the short-acting side, last year, Eli Lilly came out with an authorized generic (AG) Humalog (insulin lispro), Novo Nordisk came out with an AG NovoLog (insulin aspart). They both came out at about a 50% discount. This, again, lowers the out-of-pocket costs to consumers and there's been a lot of talk about drug pricing and insulin pricing for diabetics. So, there's been a lot of pressure for these companies to come out with these lower-cost opportunities. I think one of the unexpected consequences of these AGs is it may have prepared both Novo Nordisk and Eli Lilly for future competition to their NovoLog and Humalog products, as there are some of these products in the works. Sanofi has Admelog which is a copy to Humalog, just recently approved, and then they also have a NovoLog product in phase 3. Sanofi is trying to get in the short-acting game. Mylan has a product that is a potential NovoLog biosimilar as well. Of note, none of these products that I just mentioned—Admelog or Sanofi's NovoLog, or Mylan's potential biosimilar to NovoLog—none of these are interchangeable yet, but we could see that these manufacturers would apply for interchangeability and that could change the landscape and the insulin market in the future.