Upcoming Biosimilars and the Impact of IRA: Key Takeaways From Jeffrey Casberg

In an interview with The Center for Biosimilars^®, Jeffrey Casberg, senior vice president of pharmacy at IPD Analytics, discussed key products facing upcoming generic and biosimilar competition. He highlighted the importance of monitoring ustekinumab biosimilars, which are set to launch in early 2025, and aflibercept biosimilars, which may be delayed until 2025 or later. Casberg also addressed the impact of the Inflation Reduction Act (IRA) and pharmacy benefit manager (PBM) legislation on drug pricing, predicting increased transparency and changes in benefit designs.

He touched on the potential of value-based pricing models, suggesting they may offer opportunities, particularly for high-cost therapies, but are unlikely to become the dominant pricing strategy. Casberg identified three promising specialty drugs: donanemab for Alzheimer disease, resmetirom for nonalcoholic steatohepatitis, and Winrevair for pulmonary arterial hypertension.

Regarding the FDA approval of denosumab and tocilizumab biosimilars, Casberg noted their potential impact but cautioned that pricing competition might be limited due to the small number of manufacturers. Finally, he observed that pharmacy and therapeutics committees are now focusing more on orphan drugs, given their unique challenges in efficacy, safety, and cost evaluation.

With brand patents expiring, which products about to face upcoming generic and biosimilar competition do you think stakeholders should be keeping their eye on?

Casberg: Yeah, there are a couple products coming down the road that would be losing exclusivity. The first one I'll hit is Victoza [liraglutide], it's a GLP-1 [inhibitor]. You can't talk about pharmaceuticals today without talking about GLP-1 [inhibitors] and weight loss.

So, Victoza was kind of a big advance back in its day. It was the first once daily GLP-1 [inhibitor], once daily subcutaneous administered injectable product. It has less nausea associated with it than its previous predecessor, Byetta [exenatide]. It was also the first GLP-1 [inhibitor] that had cardiovascular positive studies for cardiovascular effect. Great drug but I don't see it really helping with this whole GLP-1 [inhibitor] shortage and weight loss issue.

If you look at Victoza and even Trulicity [dulaglutide], they both have about 50% the weight loss that Ozempic [semaglutide] and Mounjaro [tirzepatide] have so I don't see all of a sudden a big rush to go to Victoza generic because number 1: it's once a day, and number 2: it doesn't have the weight loss that some of the big products that you're hearing about every day have. So, that's Victoza, that'll be coming shortly here in June. I think there could be quite a few generics.

Two others, Tasigna [nilotinib] and Sprycel [dasatinib]. They're both tyrosine kinase inhibitors similar to Gleevec [imatinib mesylate], great drugs in oncology, pretty expensive therapies, and we should get quite a few generics and a good amount of price reduction there.

Then moving over to the biosimilars side, Stelara [ustekinumab] biosimilars are coming. Everybody's been talking about Humira [adalimumab] and 9 or 10 companies bringing those [biosimilars] to market but almost just as big, Stelara is a big drug—$15 to $20 billion product—and it also has 8 or 9 manufacturers lined up to bring products to market. We'll have to see if the adoption by payers is similar or quicker, we're just starting to have some success and conversion of Humira to biosimilars. We'll have to see how the payers adopts Stelara [biosimilars]. Maybe they've gained some more confidence and learned a little bit from the Humira introduction. We'll have to see and Stelara will be coming early in 2025. Amgen has the first product out but then pretty quickly thereafter, several other products will hit.

Stelara in early 2025, Eylea [aflibercept] biosimilars in the ophthalmology area, for age-related macular degeneration. We had Lucentis [ranibizumab] biosimilars come out with a couple of biosimilars recently and those biosimilars have done pretty well.

Eylea, we're watching, we don't know if it's going to come out this year, or in a year or 2. There's an opportunity this year, but IPD, the company I work for does a lot of predicting of this and we think it actually may not be in 2024, it might be 2025 or 2026 before we get Eylea, but watch for that. I had mentioned Victoza, Trulicity is a $16 billion GLP-1 [inhibitor], and it's biosimilar [could be] out in 2027. Something to plan for by the payers.

Do you foresee any policy changes or market forces that could significantly alter the cost landscape for both branded and generic drugs in the near future?

Casberg: So policy or legislation, everything is about politics. I guess I'll mention 2 things. I'll mention the IRA, the Inflation Reduction Act, and I'll mentioned PBM legislation. Those would be the 2 hot ones on the IRA side, we just had the first release of the negotiated drugs and which drugs they are. We'll be getting MFPs [maximum fair prices], a new acronym for drug pricing, those will be announced coming up soon.

We're going to have the out-of-pocket cost of Part D reduced to the max of an out-of-pocket cost to $2,000. That's big for patients, impactful to manufacturers, and payers. Now they're going to have to deal with different benefit designs and how they're going to market the drug and price the drug or how payers are going to make the benefits work with the new $2,000 max, so there is something for everybody there.

Then 2025 redesign, for the Inflation Reduction Act, there's also quite a few different benefit designs changing for 2025. There's price hike penalties so the manufacturers have to watch how much they're raising the prices of their drugs. If they go up too high, too quickly, then they get these penalties against them. The IRA has a number of different things, pretty complex, and everybody's paying attention to that.

Then on the second hand, it would be PBM legislation. I guess it depends on who you are and your feeling towards PBM legislation. I think it probably just comes down to more transparency. Every business has to make money and PBMs have done it. Somebody could argue they did it okay. Some say it was all smoke and mirrors but I think there's legislation now to have more transparency on PBMs. We'll see how that rolls out but a lot of discussion up in Washington on that these days.

Value-based pricing models are increasingly being explored. How do you think value-based pricing will impact the development, approval, and access to new drugs?

Casberg: So value-based pricing, you hear a lot about it. You hear people trying to implement it, manufacturers bring proposals to payers on value-based pricing models. What we don't hear of are the results and if they are working or not.

I don't know in the long run, if value-based pricing will be the 'be all and end all' and change the way drugs are paid for in the United States. I'm going to say no but I think there's some value to value-based pricing and in how you look at drugs and evaluate them.

I think especially some of these high cost therapies have opportunities for some value-based models. As I was saying earlier, there's more and more of these high cost, really expensive products and looking at outcomes and measuring outcomes, that kind of thing are for these gene therapies and other expensive therapies.

I'm not saying value-based pricing will take over but I think there's opportunity in the future for use of them.

In your view, what are the top 3 promising specialty drugs currently coming down the pipeline and why should stakeholders be keeping an eye on them?

Casberg: The first one I'll talk about is donanemab for Alzheimer's disease by Eli Lilly; it's an amyloid-β inhibitor for early Alzheimer's disease. It would be a little bit different than Leqembi [lecanemab-irmb] from Biogen, which was fully approved more recently.

Donanemab was originally going to be approved beginning of 2023, so over a year ago, but it has had a little bit of a storied pathway to approval. We were watching for an approval here any day during this last month or so, then out of the blue, there was an announcement that the FDA has requested an FDA Advisory Committee meeting.

If I'm a manufacturer, not really happy about that; you never really want extra scrutiny on your drug. I'm sure they're going to talk about the dosing regimen, the potential for shorter duration of therapy compared to Leqembi probably the ARIA [amyloid-related imaging abnormalities] side effect profile. They haven't given us a date for that FDA Advisory Committee meeting. I would anticipate a date being announced any day and I still think there's opportunity for approval before the end of 2024.

I think one of the other products that is exciting is resmetirom, or Rezdiffra. for NASH [nonalcoholic steatohepatitis]. First product approved for NASH. Again, a therapeutic area we've been waiting for therapies now for maybe 10 years. Finally we do have an approval. Congratulations to Madrigal on that, getting their product over the finish line.

A once daily, oral product. It showed signs of efficacy and NASH resolution and fibrosis improvement. Prescribing information did not include discussion of the need for biopsy in diagnosis. So, to diagnose NASH, now called MASH [metabolic dysfunction-associated steatohepatitis], the gold standard is liver biopsy, but that's pretty invasive. You can also use noninvasive therapy testing to get diagnosis of staging of NASH in the liver. They did not have that, which was a plus for Madrigal.

It would be interesting to see how the payers set up their criteria for approval. There's a whole lot of population out there that could be treated with this, so that's another big approval that just occurred.

I'll just mention one other recent approval. It's called Winrevair for pulmonary arterial hypertension, sotatercept, by Merck. Winrevair is the brand name.

It's a new product for PAH, pulmonary arterial hypertension. It's a new mechanism of action, and has the potential to be more disease modifying—the other therapies out there are more symptomatic treatments—and probably early on will be used as add-on or [in the] second or third line. But I think as physicians get used to it, they could move it up in therapy.

It is pretty expensive: $240,000 for most patients, could be $480,000 for some patients. It's a weight-based dosing, so 1 vial or 2 vials. I think it's subcutaneous every 3 weeks, and it can be self-administered or professionally administered.

What is your reaction to the FDA approval of the first denosumab biosimilars?

Casberg: So denosumab biosimilars, there was 2 approved; Wyost [denosumab-bbdz] and Jubbonti [GP2411]. The Jubbonti is for Prolia, the Wyost is for Xgeva. One is more oncology based, one is more osteoporosis based.

They were approved, but there's no announcement on when they're going to be launched. We're thinking they might even be delayed in launch till 2025.

With only one manufacturer coming out, Sandoz, with both of those, we'll get some discount on the brand and reference drug but it's not going to be significant. It's not going to be like the Humira [adalimumab] situation with 9 or 10 biosimilars.

What are your thoughts on what the launch of the first tocilizumab biosimilar means for patients with autoimmune conditions?

Casberg: So Actemra [tocilizumab] is actually IV [intravenous] and sub-q [subcutaneous]. I think that the 2 products launched, Tofidence [tocilizumab-bavi] is IV from Biogen, and then Tyenne [tocilizumab-aazg] is both IV and sub-q, and that's from Fresenius Kabi.

For the most part, Actemra is used in rheumatoid arthritis, a couple other conditions as well. Getting biosimilars in a different therapeutic area, including Actemra, that will be a big advancement. That's 2 biosimilars, so we will get a little competition there on pricing, but I don't know if I can predict what the discounts will be—maybe, 20% to 30% off.

How are pharmacy and therapeutics committees likely to approach new pipeline drugs, considering factors like efficacy, safety data, and potential cost compared to existing options?

Casberg: P&T [pharmacy and therapeutic] committees are pretty standard in their approach on how they review drugs for formulary inclusion. It really comes down to safety, cost, and efficacy.

I think in today's world, the only difference is that there's a lot of these new orphan drugs which don't have a lot of competitors, so the P&T committees have to look at a drug on its own or a small number of patients, so they really look at the efficacy opportunity—which patients should get the drug, and what the criteria can be.

It's a lot less managing 4 or 5 drugs in a therapeutic area and comparing the pros and cons of drugs that are very similar. Nowadays, we're comparing a million-dollar drug which has no competition and who the patient should be and what the criteria should be. So there is a little shift in reviewing drugs from multiple drugs in 1 therapeutic class to orphan drugs.