IPD Analytics Experts Discuss Humira's Influence on Biosimilars

CfB: Hello, I'm Matthew Gavidia. Today on MJH Life Sciences News Network, The Center for Biosimilars is pleased to welcome Leslie Fish, PharmD, vice president of Clinical Pharmacy for IPD analytics and Jeffrey Casberg, vice president of Clinical Pharmacy for IPD analytics.

So, important litigation is now completed, and we now know the path to competitor biosimilars to adalimumab. Can you discuss the significance of this progress and what it means for the adalimumab market in 2023?

Casberg: Sure. Here at IPD, we have been watching for potential biosimilar Humira [adalimumab, AbbVie] for quite a few years now. We thought there could have been a biosimilar launch as early as 2019, or even 2020 [or] 2021. But as we watched the trials proceed between AbbVie and these competitors, AbbVie was winning these trial cases. The result of AbbVie winning is biosimilar manufacturers of Humira have signed what's called settlement agreements. So, they've sat down with AbbVie and signed a document stating that they won't launch their biosimilar product until x date. Currently, there's about 9 settlement agreements signed. Within those 9 settlement agreements with 9 manufacturers, 5 of them have approved products already. One of the reasons why we speculate that the biosimilar manufacturers sign these so-called settlement agreements is that if they had pushed and won in court early, they could have launched, but they probably would not have been able to launch with the full label. In other words, all the indications wouldn't have been there. So, we speculate at IPD that 1 of the motivations to sign the settlement agreement is AbbVie then gave them the full label to come out in 2023. So again, there are 9 manufacturers that have signed. 5 [have been] approved currently and there could be a number more on the way.

CfB: With at least 5 and potentially 9 adalimumab biosimilars hitting the market in 2023, what kind of an effect on pricing do you anticipate?

Casberg: So, the United States market has not been as robust in biosimilar uptake. We think that actually the Humira [biosimilars] launching in 2023 could be the launching point or turning point of biosimilar adoption in the United States. Humira could be to biosimilars what Prozac was to the generic patent cliff in the 1990s. Once Prozac [fluoxetine] hit, generics just took off, and the utilization of generics became dominant. We think that Humira being a dominant product, that it could be the same launching-off point [for biosimilars] in 2023. Humira [biosimilars] also would be the first self-administered biosimilars. To date, all the biosimilars launched have been primarily professionally administered products, so, Humira [biosimilars] will be unique. We also think that with all these competitors lining up, they're kind of looking for unique ways to differentiate themselves instead of just being another Humira biosimilar. A couple points I'll mention are that Boehringer Ingelheim is going for interchangeability for their Humira biosimilar. It puts a different twist on their approval and gives them a feather in their cap. Or a little bit different way to differentiate themselves is Amgen. Amgen is going to have a biosimilar Humira, but they're also going to have a family of biosimilar products and all their traditional biologics. So, they'll have biosimilar Humira, Avastin [bevacizumab], Herceptin [trastuzumab], Remicade [infliximab], and Rituxin [rituximab], along with their own products Enbrel [etanercept]; Neulasta [pegfilgrastim]; Neupogen [filgrastim]; and Epogen [epoetin alfa]. So, [Amgen] could come to a payer and do a bundling thing where they offer an array of biosimilar products, and that could be an edge to them.

CfB: Why are there so many adalimumab at biosimilars in the works?

Casberg: Well, money talks, I guess. Humira is the largest-selling drug in the world. [It made] $22 billion in 2019. It's by far the largest biosimilar opportunity. Even though it's a big opportunity, there is a hurdle out there in that, in 2018, AbbVie launched a new version of Humira. It's a new formulation, it's the 100 mg/ ml, the original formulation was 50 mg/ml. The new formulation is also buffer-free and [with] a smaller needle, and the purpose of that was to reduce injection site pain. In the payer world, we hadn't heard a lot of complaints about that, but it seems that the new formulation is catching on very quickly. The new formulation was launched in July of 2018. If you look at January of 2020, they've already converted about 66% of the market share to the new formulation. So, there's a question on how much of a hurdle that will create, because by the time we get to 2023, 80%- or 90%-plus could be on the new formulation, and will it be an effort to get the patients to switch back to the traditional 50 mg/per ml formulation? The thought is that if the biosimilars come in at a big enough discount, money will talk again, and the payers will convert the patients. But on the other hand, AbbVie could go on the offense and try to compete on price with the biosimilars and maintain market share. So, it remains to be seen how that conversion goes.

CfB: So, Leslie, whereas biosimilars so far have been concentrated among a limited number of drug types, you anticipate biosimilars emerging for 14 new drug classifications by 2024. Can you discuss these developments and identify some of the most significant biosimilars that might emerge?

Fish: Yes, so I'm going to run through a few of them, which could be fairly significant, and then I'm going to list them right now. So, you could have Lucentis [anibizumab] in 2020 to 2021 and Eylea [aflibercept] in 2023. Another fairly significant one would be Tysabri [natalizumab], which could come around 2022 or 2023. There's one that I'm going to speak to but a little bit later, Soliris [eculizumab] in 2022, and I'm going to explain why it can be a very complicated situation. We also have Kadcyla [ado-trastuzumab emtansine] in 2025 and Erbitux [cetuximab] in 2023. Those are both oncology agents. Then we have Xolair [omalizumab] in 2023, a potential Botox [onabotulinumtoxinA] in 2023 or later, and Synagis [palivizumab] in 2023 Looking at a different classes, we have Stelara [ustekinumab] either in 2023 or 2024, or Orencia [abatacept] in 2023 or a little bit later, Simponi [golimumab] in 2024, and Cimzia [certolizumab pegol] in 2024. Finally, we could see an Aranesp [darbepoetin alfa] in 2024. Aranesp could be competing with other ESAs [erythropoiesis stimulating agents], but it also could be competing with the hypoxia-inducible factor [HIF] inhibitors, which would be at the end of this year, Roxadustat [FG-4592], which is an oral product. If that's approved, the Aranesp biosimilar would be competing with those HIF agents.

So, a few words about Soliris. It's very interesting. As I said, there could be a biosimilar eculizumab in 2022. Right now, Soliris is approved in the following areas: It's approved of our paroxysmal nocturnal hemoglobinuria [PNH]. It's actually approved for atypical hemolytic uremic syndrome [aHUS], myasthenia gravis, and neuromyelitis optica [NMO]. The reason that I'm telling you that it's approved is because I also have to talk about another product [garbled]. Soliris is actually given often intravenously [IV]. Ultomiris [ravulizumab-cwvz] is also IV, but it's given less often. Alexion, the manufacturer, has stated for anybody with PNH that they would like to convert at least 70% of patients from Solaris to Ultomiris. Again, these are people with PNH. Ultomiris also has [an indication for] atypical hemolytic uremic syndrome. It is going after the NMO and it's also going up to ALS [amyotrophic lateral sclerosis]. Alexion has stated that they have been fairly successful in switching people from Solaris, which has to be given more often IV, to Ultomiris. So, what I'm saying is by the time the biosimilar eculizumab is approved, we actually could be seeing very few patients on Soliris because they've been switched over to Ultomiris. Something else that is happening at the same time is that there are 2 branded products. One of them is inebilizumab and another is satralizumab. Both of these pipeline-branded products are looking to get approval in NMO and they could also be around at the same time. So, the Soliris biosimilar can see a lot of competition at the time it comes out. I like to say just a little bit of word about Kadcyla because earlier I talked about Herceptin and the use of it and trastuzumab biosimilars. [Garbled.] With patients, if the ongoing studies showed that earlier use of Kadcyla is actually appropriate, physicians [will] move from prescribing Herceptin to Kadcyla. So, it's quite interesting that there could be a biosimilar [for Kadcyla] in 2024, [which is] really not that further along than Herceptin.

CfB: So, Leslie, will we see multiple entrance for 1 or more of these 14 classifications?

Fish:

There could be for certain ones that I talked about. There are definitely more than 1.

CfB:

So, Jeff, there have been similar legal struggles to bring an etanercept biosimilar to Amgen's Enbrel to market. Can you tell us about the progress here?

Casberg:

Sure. So, just to give comparison, on the Humira side, there were all kinds of court cases and it really wasn't 1 decision that drove Humira [biosimilars] to be launched in 2023. There were quite a few court cases and a legal web involved with the Humira situation. The Enbrel/Amgen situation was a little more black and white. There was 1 court case and it was Amgen vs Sandoz. On August 9, 2019, Amgen prevailed. So, what that means is it's highly likely that Enbrel [biosimilars] will be launched in 2029 as opposed to anytime soon. Sandoz has appealed and there's an opportunity that the decision in favor of Amgen could be overturned. But at IPD we think that's unlikely and we're planning for a 2029 Enbrel biosimilar launch. Competitors have lined up for Enbrel biosimilars—there are 2 approved currently. One is Erelzi [etanercept-szzs]from Sandoz. The company on the other side of the court case, their Erelzi was approved in 2015 but it looks like they're going to have to wait a number of years to launch their Erelzi. And then Eticovo [etanercept-ykro] from Samsung Bioepis was approved in 2019 as well. Both products have full labels. There's no concern about lack of indications in the labels, but it does look like we're looking at 2029 unless there's a change of events and the court case was overturned. Other candidates in line: Coherus BioSciences has an Enbrel in line and also Lupin is working on an Enbrel biosimilar. So, not the double-digit candidates like you're seeing on Humira, but you're seeing quite a few as opposed to a $22 billion Humira product. Enbrel is about a $5 billion-a-year product. So, [there's] a little bit less competition.

CfB:

And again, just to further stress, what is the market potential there?

Casberg:

Yep. So, Enbrel had $5 billion in sales in 2019 versus $22 billion for Humira, the highest-selling drug in the world.

CfB:

And finally, Leslie, do you have any thoughts on when we might see the first interchangeable biosimilar? And what that might be?

Fish:

Yeah, that's a very good question. First, let me say that we're aware of 3 products that we think are attempting to obtain interchangeability designation, and you have to keep in mind, though, that these are potentially interchangeable products. We probably will not know for sure until the FDA approves them and they come out and we look at it from labeling. That being said there's an infliximab biosimilar for Remicade. It will most likely not be out for a year or maybe a little bit more. We do believe that the studies needed for the interchangeability have been completed. The next product is an adalimumab biosimilar for Humira, and is by Boehringer Ingelheim, called Cyltezo [adalimumab-adbm]. It would be launched around 2023. We also believe that they're doing the studies for the interchangeability and we do believe that those have also been completed. Lastly, there could be a biosimilar for NovoLog, or insulin aspart, by Sanofi, that could be interchangeable, and it does look like those interchangeable studies or the standards needed for interchangeability of that product have been completed.

CfB:

To learn more, visit our website, centerforbiosimilars.com, I'm Matthew Gavidia. Thanks for joining us.