Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

CfB: I'm Tony Hagen with The Center for Biosimilars. Today, we're speaking with Sean McGowan. He's the senior director of Biosimilars for AmerisourceBergen. Welcome, Sean.

CfB: Sean, can you comment about biosimilar approvals in 2021? It was a pretty interesting year, I think, even though we had just a few.

McGowan: Yeah, it was it was quite a year of firsts for biosimilars in 2021. And in starting with the biggest approval and launch onto the market with the Semglee [insulin glargine] product from Mylan/Viatris. In July of 2021, the FDA approved the first ever interchangeable biosimilar product in Semglee, an insulin product indicated for treatment for type 1 and type 2 diabetes. That product launched in November with actually 2 versions of branded and an unbranded version. So, Semglee's entrance into the retail pharmacy, including mail order pharmacy, space makes it the first biosimilar to be covered under patients’ pharmacy benefit or Part D plans. So, kind of a first of its kind.

And the interesting thing about the Semglee launch is that it's got the potential to positively impact millions of more patients with its availability at the pharmacy counter. And this is definitely going to be a preview of what's to come with the future of Part D biosimilar launches. Not to mention that Semglee has been recently adopted on to a couple of national PBM [pharmacy benefit manager] formularies, including Express Scripts and Prime Therapeutics.

As we look into other therapeutic areas in 2021, we also saw the first biosimilar approval in the retina-ophthalmology space with Biogen's Byooviz, which references Lucentis [originator ranibizumab]. In October, we saw the FDA approved Cyltezo, making it the first interchangeable biosimilar product referencing Humira [originator adalimumab] and only the second interchangeable product ever to be approved by the FDA. And just to clarify, Cyltezo already had FDA approval. It was that interchangeable designation that received approval back in October.

Then in late December, right before the end of the year, the FDA approved 2 other biosimilars: an insulin glargine product from Lilly and then Yusimry, a biosimilar referencing Humira from Coherus [Biosciences]. So, all of these approvals and entrances in 2021 indicate to me that the FDA is getting back on track to reviewing and approving these products so patients can access these treatments. Also, it's an indication that the market continues to expand.

CfB: Just a footnote to that introduction. The Semglee launch was both a branded and unbranded. Can you shed any light on why that strategy was chosen by Biocon?

McGowan: Yeah, so Mylan and Viatris are the commercial partners and US Biocon is the manufacturing partner and from what I can see and what's been published publicly is that there's actually a non-biosimilar version of Semglee already on the market that had launched back in [the] summer of 2020. And that product came out on the market with a heavily discounted WAC [wholesale acquisition cost] price and looked to be launched to compete more in the Medicare Part D and Medicaid space or those cash paying patients. And then as the biosimilar products were being approved, Mylan/Viatris was looking to compete both in the commercial space as well as that Medicare/Medicaid space. And so, they've kind of launched the same product under 2 different names, 1 branded and 1 un-branded to fit specifically into some specific payer markets. And so, we're less than a quarter into the launch of this product and time will tell on how that strategy actually plays out.

CfB: Thanks. So, at the GRxBiosims meeting, which is a fairly informative conference, there were several FDA representatives speaking and they seemed a lot more focused on biosimilars than they had been in the past. Coming out of the pandemic, or at least, maybe partway through the pandemic, what does this signify, do you think?

McGowan: Yeah, it was great to see the quality and safety of generic and biosimilar medicines was a top priority for our industry and a key theme of the meeting. So, I'd say this progress is motivating and moving in the right direction. The FDA has also promised to provide more clarity on the handling of the interchangeable designation, which I think everyone is really interested to gain some additional clarity and insight into that designation, as we see more and more products receive that designation in the future. It's also encouraging that the pharmacy benefit managers have been moving interchangeable biosimilars onto their preferred formularies like they've done with Semglee and that pharmacists in the retail space now get a chance to experience a biosimilar product. But overall, there's still a lot of basic education required about biosimilars to generate more confidence in their use across all stakeholders in the supply chain.

CfB: So, you have a terrific pipeline report on biosimilars, which is updated regularly. Can you tell us what we can look forward to in biosimilars in the insulin market in 2022?

McGowan: Yeah, sure. So, with 2 approved insulin glargine products, we'll see that market become more and more competitive once Lilly announces the launch timing of their insulin glargine that just recently received approval. We're seeing a product being developed by Sandoz that's currently in phase 3 trials. Last week, we saw an announcement that Biocon's application for its insulin aspart received a CRL [complete response letter] from the FDA but Biocon seemed to be confident that they're going to be able to provide the additional data that's required there. So, we'll see some additional markets either open up or expand in the near future.

We also have another insulin glargine from Lanett that's in the preclinical clinical trial stage. And so, we're expecting, at least based on what they've disclosed, that their clinical trials will start Q1 or Q2 in 2022. And then they're looking for FDA approval in 2023 and a potential launch in 2024.

Finally, there are about 5 rapid-acting insulin biosimilars currently in the pipeline for manufacturers including Biocon, Viatris, Sandoz, and Sanofi. And they're all in different clinical trial stages at this time, from preclinical to phase 3. So, I anticipate more of these insulin products to continue to be developed and hopefully approved and launched onto the US market in the coming years.

CfB: So, this year is shaping up to be a positioning race for adalimumab biosimilar market entry. They don't actually arrive until 2023 but what can you say about the positioning that's going on and how companies are looking to stand out in this market?

McGowan: Yeah, you're absolutely right. 2023 is going to be the year of the Humira biosimilars. And I think we're all anxiously waiting to see how this plays out. And it is going to be 1) very interesting and 2) I think a bit complicated with the number of manufacturers that are already set to launch products in 2023 [n = 7]. And then, how are they going to compete against the existing versions of Humira? So, as far as timing is concerned, Amgen will be first out of the gate with their product launching at the end of January 2023. And they're going to have about a 5-month head start over the next tranche of manufacturers that'll bring their Humira biosimilars to market. So, the next group will have Organon, [Boehringer Ingelheim], and Coherus launch their products in that middle summer timeframe, kind of end of June and early July. Then, we're going to see Viatris, Sandoz, and Pfizer launch their products between August and November in 2023. And then, we also know that Teva, in partnership with Alvotech in the development of that Humira biosimilar, is waiting for FDA approval, but launch timing is really unknown at this point.

CfB: As an aside for the Amgen now, Amgevita [adalimumab biosimilar] will have that 5-month head start. What do you think will be the lasting impact of that advantage?

McGowan: Right now, Amgen definitely is positioned to have the advantage from that timing standpoint and that head start over everybody else. Just a couple of things to take into consideration, you're absolutely right that 2023 is going to be an exciting year, but keep in mind these manufacturers are absolutely focused not only on 2023 but the several years to come after that. And so, 2023 is definitely going to be a year where the staging has taken place. Yeah, there's going to be a bit of an advantage for Amgen, and they're going to have a lot of critical decisions to make around pricing, PBM coverage, support services, patient and physician education, which is all going to have an impact on everybody else that comes after Amgen. So, I think a lot of things are going to play out, but we can't discount the fact that in the years 2024, 2025, and beyond are going to be years where these products are going to be competing. But 2023 is most certainly going to be probably the most exciting, just given the timing and the number of products that are going to come onto the market.

CfB: And 1 more question on the adalimumab pricing. What could be the effects on pricing of having so many competitors arrive on the market at the same time? Do you think that there will be a sudden drop, or do you think that given the settlements that they made with AbbVie [reference adalimumab manufacturer] that that is not going to occur?

McGowan: Yeah, that remains to be seen. I think the pricing piece is going to be interesting, just because they're going to be so many products out there and then you have this long history of AbbVie's pricing on this product. But I think a lot of the activity is going to be driven by the PBMs in which products they decide to adopt, put on their formularies, and switch patients over to. So, it's really going to be incumbent upon the manufacturers to be negotiating those deals with the with the PBMs and then which products are being adopted and which products are left off of formularies. So, at the end of the day, given that this is that pharmacy benefit space, I think the PBMs are going to play a very critical and influential role in the launch of these products.

CfB: Okay, so, etanercept has been a bit of a disappointment in terms of bringing biosimilars to market. The 2 contenders have not succeeded in breaking through the patent barriers on Enbrel [originator etanercept]. So, is there a possibility that other etanercept biosimilar makers will step forward?

McGowan: Yeah, this is certainly disappointing news for the biosimilar market, and it's been an ongoing legal battle across the last several years, especially with 2 FDA approved products out there. But the litigation rulings at this point seem to be pretty definitive. I don't foresee any manufacturers continuing to pick up the torch and continue the legal battle here, which, again, is unfortunate and it doesn't seem like we'll see an Enbrel biosimilar on the market in the US for the next several years.

CfB: In ophthalmology, ranibizumab has taken some interesting turns. Susvimo is a biobetter, some might say, and has an implant reservoir vs an injectable, which could offer great convenience to patients. Could this be a disruptor in the ranibizumab market and how could it affect biosimilar competition?

McGowan: Yeah, it’s a new market and molecule for the biosimilar markets, which is really exciting. So, it's going to be a very interesting market to watch evolve. Not only have we seen this implantable device launch onto the market, we also know that Roche/Genentech is developing their faricimab molecule, which will have retina-ophthalmology indications. So, we'll have to see how successful they will be at launching that product, which will have patents and exclusivities if and when it's approved, and then how successful they'll be in converting patients over to that product. We also have another organization and company with Outlook Therapeutics actually developing a bevacizumab product specifically for the retina-ophthalmology indications. So, that's going to be a little bit of a nuanced wrinkle and addition into an already complex and competitive market.

But on the biosimilar front, there's currently only 1 approved product from Biogen with Byooviz. And we're anticipating at least 3 other biosimilars referencing Lucentis to come onto the market in the next 2 to 3 years. So, Biogen is most certainly going to be the first product on the market in this space and what's been announced is a mid-2022 launch for that product. But it's going to be very interesting to see how the practitioners and the practices get educated on biosimilars, since they most likely have not utilized a biosimilar in the past, and how to build those into their care plans and adopt these products. Given the complexity and how heavily competitive this market is, given the innovator company's position, a new branded product coming to market, and then several biosimilars, it's going to be another very interesting market to watch evolve.

CfB: Yeah, affordability is a tremendous issue in ophthalmology. So, what else might move the needle in the biosimilar pipeline events in 2022?

McGowan: Looking ahead to calendar year 2022, I think there are a few opportunities and challenges to look for. So, going back to Semglee's launch and the availability of 2 versions, a branded and unbranded, we'll be watching closely as to how these products compete in the commercial market vs the Medicare/Medicaid or Part D plans. So, which version of the product is going to get adopted and how quickly can it grow and into what levels? And then what learnings can manufacturers glean from the strategy that Viatris has taken, and can they take those learnings and apply them to other biosimilar markets, and I think Humira is 1 specifically that jumps right to the front of my mind. So, can this type of strategy be replicated in other markets? In staying on the topic of Humira, the approval and the launch of Semglee will most certainly act as kind of a dress rehearsal for bigger biosimilar market entrance expected in the Part D space in 2023. So, having an interchangeable product and having a Part D product, a pharmacy benefit product, is most certainly going to provide a lot of learnings and education around how the pharmacists' handle these products, how the pharmacy benefit managers handle these products, how they're positioned on the formularies, and how that interchangeable designation is treated at the pharmacy counter.

And then there's some excitement in the medical benefits of the Part B space with the forthcoming launch of the first biosimilar in the retina-ophthalmology space in Byooviz, which references Lucentis and we've talked about just a minute ago. Again, that launch is expected to happen mid-year in 2022. 2022 is also going to be the year where everyone is preparing for the watershed moment of the 7 plus biosimilars referencing Humira coming onto the market starting in 2023. And with the 7 plus Humira biosimilars entering the retail and specialty pharmacy space, a whole new customer group and market will be introduced to biosimilars. So, again, kind of going back to my point earlier around the education piece and how this continues to be a critical element to improve the adoption of biosimilars, the aperture expands exponentially as these retail pharmacy and specialty pharmacy products come onto the market.

And then just some considerations for the biosimilar market moving forward. We'll continue to watch how manufacturers of innovative products respond to biosimilars. A great example, Janssen towards the end of 2021 launched an unbranded version of Remicade [originator infliximab] similar to how Semglee was launched both branded and unbranded. Now, we've got an innovator product in the Part B space with a branded and unbranded [version]. We'll most certainly make note of whether or not this strategy is successful and then whether or not other innovator companies adopt a similar strategy. We're also expecting to see a new set of manufacturers launch biosimilar products into existing markets, as well as new biosimilar markets like Biogen with their Lucentis biosimilar. Finally, existing biosimilar markets will become more competitive with new entrants. All of this is really great in my opinion because these manufacturers continue to see an opportunity for biosimilars, and patients will benefit from increased competition that helps improve access and affordability.

CfB: Terrific, Sean, thanks. Finally, the Build Back Better Act has been through a lot of drafts, and we don't know whether it's going to see the light of day. What are your thoughts on how this might affect biosimilars in the final version, if there is one?

McGowan: Yeah, that's a great question and I know a lot of focus on the Build Back Better Act was paid in the November timeframe before the legislators shut it down for the end of the year. We're going to be following this very closely to see what policies actually make it into the bill, in whatever way shape or form that happens. I think we all want to see policies that continue to support a market that allows for biosimilar competition, encourages manufacturers to invest in the space, and helps to bring down drug prices and the overall cost of care. Despite all the challenges and hurdles the biosimilar market has had to overcome across the last several years, biosimilars have most certainly delivered on their promise to expand access, drive down costs, and deliver on savings.

CfB: Thanks very much, Sean. It's great talking with you again about biosimilars at The Center for Biosimilars.

Videos

Sean McGowan, senior director of Biosimilars for AmerisourceBergen, forecasts potential biosimilar approvals and launches in 2022 as well as offers insights into how emerging biosimilars will impact the market and pricing in the coming years during an interview.

AmerisourceBergen Rep Previews the Year Ahead for Biosimilars: What’s Coming Down the Pipeline in 2022?

The Economic Alliance of Michigan is a group of employers who share strategies for improving the coverage of their membership. In this interview, Tony Hagen, senior editor for The Center for Biosimilars®, interviews Bret Jackson, president of the group, about recent achievements and how these were accomplished.

Jackson notes the importance of payer collaboration and enthusiasm for biosimilars. He also states that a key to the success so far has been educating patients and providers about biosimilars.

Through a combination of these strategies and utilization management, employers have found that employees have made the conversion to biosimilars successfully, achieving, in some cases, standout savings, and easing financial toxicity for patients, Jackson says.

Bret Jackson, president of the Economic Alliance for Michigan, notes that Ford Motor is a biosimilar success story, having saved a significant amount of money on just a handful of drugs. 

Industry Group Representative Discusses Biosimilars in Michigan

The International Generic and Biosimilar Medicines Association has appointed a new chair to lead the manufacturers trade association through the coming year.

Vivian Frittelli, MBA, ACIS, the CEO of Generic and Biosimilar Medicines of Southern Africa (GBM), is taking over from Sudarhsan Jain, secretary general of the Indian Pharmaceutical Alliance. Frittelli has also served as chair of the IGBA in the past. 

GBM is also a trade association representing manufacturers and distributors in pharmaceuticals in South Africa. The group has made expanding access to biosimilar and generic medicines a focus of its efforts. Biosimilars are as safe and efficacious as the brand-name products they reference.

Frittelli has roughly 25 years of experience working in the pharmaceutical industry. He formerly headed Hoffmann La Roche’s marketing and sales division in South Africa and later became country manager for Roche in Saudi Arabia. He has also served as regional director for the Smile Train, which works to bring surgical attention to children with cleft lips and palates in the Southern Africa region.

Frittelli has also worked for Sandoz Pharmaceuticals to establish their oncology division in South Africa.

IGBA has worked with the World Health Organization to reduce clinical trials requirements for biosimilar development, so that unnecessary measures of biosimilarity can be replaced by more modern, reliable means of verifying equivalence to reference products. Jain stepped into the IGBA chair role in January 2021.

“Despite these disruptive times, tangible progress was made under 

, which allowed the IGBA submission for the WHO Non-State Actor status, which aims to increase worldwide access to affordable quality treatment,” Jain said in a statement.

Under Jain, the IGBA in 2021 published a 

 mapping out a blueprint for expanding generic and biosimilar access worldwide, calling for fair patenting and litigation systems, harmonized regulatory frameworks across international borders, and support for new technology and new drug development, in the form of allowances for financial support for development.

“I am very pleased to take over the Chair of IGBA for the second time and look forward to building upon the strong leadership of Sudarshan Jain,” Frittelli said.

The group also noted that Jonathan Kimball, vice president of Trade and International Affairs at the Association for Accessible Medicines, wil take over as vice chair of the IGBA. Kimball has served as vice chair of the IGBA International Trade and Intellectual Property Committee.

Articles

The International Generic and Biosimilar Medicines Association has appointed a veteran member, Vivian Frittelli, MBA, ACIS, to take over as chair.

International Biosimilars Trade Group Appoints New Leadership for 2022

The pandemic may leave employers feeling as though they’re too stretched to take a risk on pushing for broader biosimilar incorporation into employees’ treatment plans, but a group of employers in Michigan in a recent 

 have shared success stories and tips for achieving success with biosimilars.

The Economic Alliance of Michigan (EAM) is a member of the National Alliance of Healthcare Purchaser Coalitions, and as such has worked over a number of years to advance biosimilar use in Michigan. Biosimilars are often significant drivers of savings in a specialty drug environment that is approaching 50% of the pharmacy counter tab, the group said.

Ford Motor is one company in Michigan that stands out for its success with biosimilars, the group explained. The company managed to convert 100% of health maintenance organization utilizers of brand drug Remicade (infliximab) to the biosimilar Inflectra and 88.1% of users in its preferred provider organization, “with no disruption to patients and no negative feedback from its members,” the EAM said.

The transition to biosimilar infliximab, a drug used to control inflammation in patients with arthritis and other autoimmune disorders, began in 2019, and 4 other biosimilar drugs were added to the program, saving Ford $5 million by 2021, the group said.

Among strategies Ford and various payers (Priority, Blue Cross Blue Shield of Michigan) have used to make their biosimilar programs a success are the following:

Persuade physicians to accept biosimilars and patients will follow. “The doctor-patient relationship is the closest and most trusted in the health care arena, and physicians can heavily and reliably influence patient decision-making.”

Build physician confidence in biosimilars by supplying analytics and data about these agents. “Share success stories such as those from Europe, where biosimilars have enjoyed wide acceptance.”

Use conferences, forums, and other presentations to reach physicians with the biosimilar message.

Provide physicians with cost and efficacy data on biosimilars. “One health plan ranked its drugs in a continuum of pricing and shared comparisons of prescribing across physician colleagues to illustrate the cost difference of prescribing biosimilars.”

Share frequently asked questions with patients.

The above examples show that persuading physicians that biosimilars should be used has been a key plank in the effort to get these agents into wider play in Michigan.

The EAM notes in its case study report that biosimilars are as safe and efficacious as the drugs they reference and are rigorously evaluated for quality by the FDA before being introduced to market. There are currently 33 biosimilars approved in the United States and 21 of those have been launched. In Europe, though, many more biosimilars are approved and in circulation. This is largely because the European Union approved its first biosimilar almost 10 years before the United States did (2006 vs 2015).

Biosimilars cost a fraction of what it costs to develop originator products, which is why biosimilars can help save money. “A report from Xcenda shows that biosimilar competition has successfully lowered the price of brand name biologics by an average of 56%,” the EAM said.

Although payers are often seen at odds with employers’ health care goals because of their rebate deals with manufacturers and pricing arrangements that often lack transparency, the EAM reported that manufacturers in Michigan have had some success in collaborating with payers on biosimilar use.

Blue Cross Blue Shield of Michigan and Priority Health have emphasized the use of biosimilars in employer health plans and, via the EAM report, noted the following:

Biosimilar drug competition with reference drugs is lowering prices of medicine overall.

Patients have been switching to biosimilars because they are in accord with the goal of reducing costs.

Biosimilar adoption has been highest in oncology, which is logical because most US biosimilars are for oncology treatment.

Health plans have been making sure copay assistance for biosimilars is available from manufacturers.

Health plans have managed to incentivize use of biosimilars by eliminating prior authorization requirements for biosimilars while maintaining it on reference drugs, the EAM said. “Removing the administrative burden for biosimilars made the transition easier for physicians and increased uptake.”

Priority and BCBSM pursued a lowest net cost strategy when it came to the choice of drugs for formulary, and this meant considering not just biosimilars but also drug wholesale costs, rebates, discounts, coupons, and other factors. Even so, one health plan managed to achieve savings not by focusing exclusively on manufacturer rebates for use of certain drug products, but by “focusing on the big picture to realize even greater savings through uptake in biosimilars,” the EAM said.

Allowing speciality drugs to be administered outside the hospital setting, which is generally more costly than homes or infusion centers, also enabled savings from biosimilars, the group said.

“Employers indicate this policy was received very favorably by members and one health plan indicated they have achieved savings in the millions of dollars from their ‘site of service’ plan,” the EAM reported.

Ford Motor recommended that considerations be made for employees to cushion the transition to biosimilars. These include:

Grandfather use of originator drugs in some cases up to 6 months.

Allow switching to biosimilars when patient treatments are renewed.

Allow case-by-case reviews in the event there is a problem and patients have special circumstances.

Some employers don’t have the resources to focus on biosimilar transition programs, especially given the pressures imposed by the COVID-19 pandemic. The EAM also noted that employers are often in the dark about what rebates or financial incentives are shared between payers and manufacturers. “In some cases, a pharmacy benefit manager and pharmacies are owned by the same firm,” and “often PBMs' best interests do not match employers’ best interests.”

Further, COVID-19 has caused worker shortages and led to employees delaying essential health care. “Employers explained that employees missed physicals and other physician visits during the pandemic, and age-appropriate preventive care was delayed or neglected. This interruption in care will create a massive increase of health care needs and will impact the system for years to come,” the EAM report said.

“COVID-19 disruptions have left employers feeling more stretched and risk averse than usual, and therefore biosimilar adoption may not be an area they can prioritize,” it said. 

Return to The Center for Biosimilars next week for an interview with Bret Jackson, president of the EAM. 

Ford Motor saved $5 million by switching patients to 5 biosimilars, and other manufacturers and employers in Michigan have achieved good results with switching programs, the Economic Alliance of Michigan reports. 

Michigan Trade Group Outlines Best Practices for Biosimilar Adoption

The Global Healthy Living Foundation is a volunteer organization that works to improve the lives of individuals with chronic conditions. Given that, the group has a natural interest in seeing improvements in patience access to critical medicines, such as biosimilars, which are equivalent to reference biologics and can help bring down the costs of treatment.

In this interview, Tony Hagen, senior editor for The Center for Biosimilars®, talks with Robert Popovian, PharmD, MS, who serves as chief science policy officer at GHLF, about a recent podcast series the group did to promote wider understanding of biosimilars. Popovian provides his impressions of progress toward biosimilar availability in the United States and the value of biosimilar education for patients and providers.

Popovian is also vice president of Health Economics and Policy for ConsenSys Health and a senior health policy fellow at the Progressive Policy Institute. To access the podcasts on biosimilars produced by GHLF, use this 

As chief science policy officer for Global Healthy Living Foundation, Robert Popovian, PharmD, MS, has a bird’s-eye view of some of the central issues of biosimilar access in the United States.

Robert Popovian, PharmD, MS, Discusses Biosimilar Progress and Education in the United States

Excitement is building at Amgen as the year 2023 draws closer and the company gets ready to launch Amjevita, its biosimilar version of adalimumab, referencing the long-reining reference product Humira, an immunosuppressive product that had $20 billion in sales in 2020.

Adalimumab is used for the treatment of multiple inflammatory conditions, including arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis, plaque psoriasis, and others.

In 2021, Amgen’s biosimilar portfolio was generating annual revenues on the order of $2 billion, but with Amjevita and 6 other biosimilars in the pipeline, those revenues could “more than double” through 2030, Amgen Chairman and CEO Robert Bradway stated at the 2022 JP Morgan Healthcare Conference, held this month.

Amjevita will launch in January 2023, giving it at least a half-year head start on half-a-dozen other adalimumab biosimilars scheduled to start entering the market in June 2023. There are no adalimumab biosimilars on the market in the United States, and Amjevita will be the first, unless other contenders are able to break through innovator company AbbVie’s formidable patent barrier protecting Humira’s exclusivity. Each of the entrants scheduled so far has settled with AbbVie out of court on market timing and royalty compensation.

Bradway also described optimism for other biosimilar launches anticipated to occur shortly after Amjevita, including biosimilars for ustekinumab (Stelara), an immunosuppressive drug for plaque psoriasis and psoriatic arthritis; aflibercept (Eylea), an ophthalmology drug for age-related macular degeneration, macular edema, and diabetic retinopathy; and eculizumab (Soliris), an immunosuppressive drug used in the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Currently, Amgen has 4 oncology-centered biosimilars on the market. These include trastuzumab (Kanjinti), bevacizumab (Mvasi), infliximab (Avsola), and rituximab (Riabni). These reference Herceptin, Avastin, Remicade, and Rituxan, respectively.

Bradway said these and the anticipated launches of pipeline products, including Amjevita, which is FDA approved, would target 11 innovator or reference products in total that by themselves generate $86 billion in annual revenue.

“Clearly, we see this as an attractive franchise from the revenue standpoint,” he said.

Humira was launched in 2002, making it 20 years of exclusivity so far for AbbVie, which has raked in at least $170 billion in global revenues during that time, according to a recent congressional investigation. 

Adalimumab biosimilars have been making inroads into AbbVie's Humira revenues in the European Union, where sharp declines in Humira revenues have been observed, and in Canada, recently a push by the Canadian public health authorities has put 

 on the radar for health care consumers in just the past month: Yuflyma (Celltrion Healthcare) and Simlandi (Alvotech). 

Amgen Chairman and CEO Robert Bradway touted the potential of 11 biosimilars anticipated to be driving revenues for the company by 2030.

Amgen CEO Touts Potential for Doubling in Biosimilar Revenue

Alvotech of Reykjavik, Iceland, has become the second biosimilar developer to announce an approval in the Canadian market for a high-concentration, citrate-free adalimumab biosimilar (100 mg/mL). The product, Simlandi (AVT02), may launch immediately as Canadian health authorities have ruled that clearance should not be impeded by litigation between Alvotech and the innovator company, AbbVie, maker of the reference brand Humira.

Adalimumab is an anti-inflammatory drug used for multiple conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn disease. In Canada, Humira, the reference product, had sales of over $700 million in 2020, according to IQVIA.

In a statement, Alvotech said that “the 40-mg/0.4-mL and 80-mg/0.8-mL presentations of Simlandi, are not subject to the statutory stay, clearing the way for the launch in the Canadian market.”

In the United States, the market for high-concentration adalimumab now represents at least 80% of the market for adalimumab, according to IQVIA, and only Humira is available there; but in Canada, there has been a history of patients not being able to obtain the high-concentration version, which is prized because of its convenience (low-volume administration) and its citrate-free formulation, which reduces the pain experienced by patients.

In Canada recently, Celltrion Healthcare also has 

 for marketing its high-concentration, citrate-free adalimumab biosimilar (Yuflyma; CT-P17).

Both Celltrion and Alvotech have obtained European Commission approval to market Yuflyma and Simlandi, respectively, in the European Union, where the market for high-concentration adalimumab represents about a 60% share of the adalimumab market, according to Celltrion. However, Celltrion has initiated launch in the European Union and Alvotech has yet to announce a launch date. The reasons for the delay have not been disclosed.

In the United States, Alvotech is entangled in litigation with AbbVie over AVT02, and it’s unclear whether this product will reach market in 2022 or beyond. Both Celltrion and Alvotech are awaiting regulatory approval to launch in the United States.

For Alvotech, the Canada Simlandi launch will be managed by JAMP Pharma Group, a Canadian company based in Montreal. Authorization was granted by Health Canada.

“We are extremely proud to be the first Canadian company to offer this value-added option at a considerably lower cost than Humira, Louis Pilon, CEO of JAMP, said in a statement.

 into biosimilars by introducing mandatory switching policies province by province and most recently in the Northwest Territories. Biosimilars are as safe and efficacious as reference products, and they hold the potential for enormous savings, as their competition forces reference drug producers to lower prices of their brand products.

Globally, Humira is the top-selling drug, netting roughly $20 billion in sales in 2020. The high cost of Humira, an estimated $77,000 per year per patient in the United States, is seen as a significant barrier to access that in some cases forces patients to make hard choices between seeking treatment with this drug and paying for other essentials.

JAMP and Alvotech said their high-concentration formulations will offer patients some flexibility in treatment: “We will also offer a unique 80-mg/0.8-mL dose to Canadian patients that will reduce the number of starting injections by 50% for the patients that require it,” said Bruno Mäder, president and chief operating officer of JAMP.

Simlandi (AVT02) is the second high-concentration, citrate-free adalimumab (Humira) biosimilar to be approved in the Canada market. 

Canada Clears Alvotech Adalimumab Biosimilar for Launch

Concerned about patient access to critical monoclonal antibody medications, including biosimilars, patient advocates in India have appealed to the country’s executive administration to spur reforms in biologics regulation to facilitate less costly and more rapid biosimilar development.

“We would like to bring to your urgent attention the unaffordable prices of biotherapeutics such as monoclonal antibodies [mABs],” said the group, which includes the Campaign for Access to Medicines, Devices and Diagnostics, India; Cure SMA Foundation of India; World without GNE Myopathy; and others.

Such conditions as cancer, COVID-19, arthritis, and lymphoma can be treated with mABs, which is why they are so important, the advocates state. 

Indian regulators still rely on comparative clinical efficacy trials of biosimilars to demonstrate that they are comparable in safety and efficacy to reference products. The advocates note that evolving world-class standards for biosimilar development are tending away from strict requirements for comparative trials. 

Although reference (originator) products undergo in-human trials to demonstrate and verify clinical value, biosimilars can largely be analyzed for comparability to the reference products in the laboratory, without the need for assembling large patient cohorts. This is because analytical testing of biologics has evolved to such a degree that in most cases it can provide much more sensitive and reliable biosimilar equivalence data than comparative clinical trials.

Advocate groups signing on to the appeal to Shri Narendra Modi, India’s prime minister, noted that the United Kingdom, following the Brexit departure from the European single market, announced it would discontinue strict reliance on comparative clinical efficacy testing for biosimilars. They also noted that the World Health Organization (WHO) is drafting guidance that endorses this approach to biosimilar development.

The WHO does not approve biosimilars although it does make recommendations of approved medicines that influence the medicines that doctors and health institutions around the globe select for use.

“An adequately powered comparative efficacy and safety trial will not be necessary if sufficient evidence of biosimilarity can be drawn from other parts of the comparability exercise,” the WHO wrote in the draft guidance.

Per-capita income in India is lower than in more-developed countries and that can add to the difficulty of affording biologics. The reform advocates cite a recent study that indicated that 80% of the global mAB market is centered in the United States, Canada, and European Union. And whereas registered mABs in the European Union and United States are 120 and 112, respectively; in India this number stands at just 36, the group said.

The primary reason for the lack of competition in the mAB market is the entry barrier due to the current regulatory framework as per the current regulation of biosimilars.

If regulations were more in step with modern science, biosimilars would become more numerous in India, they contend. “The primary reason for the lack of competition in the mAB market is the entry barrier due to the current regulatory framework as per the current regulation of biosimilars,” they state.

They explain that comparative clinical trials add significant expense and time to the development process that adds to the cost of biosimilars once they reach market and discourages producers from developing biosimilars in the first place. “Only those companies that have the deep pockets could develop biosimilar mABs and other biotherapeutic products.”

In a recent interview with The Center for Biosimilars

, Marta Baldrighi, PhD, spoke about the WHO's guidelines 

In India, an emphasis on outdated biosimilar testing has restricted market entry of these products and discouraged manufacturers, patient advocates contend. 

In India, Patient Advocates Lobby for Modernized Biosimilar Development Standards

A strong market and development push for “biobetters” is anticipated by authors of a review of biosimilar and new biologic drug development in ophthalmology. Whereas biosimilars have the same amino acid sequence and are highly similar to reference products, biobetters may be modified chemically and have a different amino acid sequence or purification process. This can improve shelf life and pharmacological effects.

Biobetters may require a much larger investment in development than biosimilars, but “the chances of a biobetter reaching the production stage are incredibly high,” the authors write.

An example of a biobetter cited by the authors is Susvimo, an ocular implant that delivers ranibizumab (Lucentis) into the eye, eliminating the need for intravitreal injections. Susvimo, a Genentech product, was approved by the FDA in October 2021. Genetech is also the originator of ranibizumab, which treats neovascular age-related macular degeneration (AMD), macular edema, and diabetic retinopathy.

In the Republic of Korea, Ildong Pharmaceuticals is developing a biobetter for patients receiving ranibizumab that is hoped to improve efficacy and lessen resistance; and Alteogen has patented an aflibercept (Eylea; also for AMD) biosimilar formulation that has an improved shelf life and resistance to heat.

“While the biobetter market is still in the developing phase, it has enormous potential to grow,” the authors wrote. In their review, they stressed a coming wave of biosimilars in ophthalmology and the importance of keeping up for clinicians.

In the United States, the patents for bevacizumab (Avastin), which is used off-label in ophthalmology, and ranibizumab expired in 2019 and 2020, respectively. Aflibercept won’t be off patent in the United States before 2023.

Bevacizumab, ranibizumab, and aflibercept are anti–vascular endothelial growth factor (anti-VEGF) therapies that stop the abnormal growth of blood vessels that lead to subretinal bleeding and harm vision. They also treat diabetic macular edema and retinal vein occlusion.

The authors counted 10 manufacturers currently with ranibizumab biosimilars approved or in development, globally. Byooviz, a Samsung Bioepis biosimilar, was approved in 2021 by the FDA and the European Commission. Other ranibizumab biosimilar candidates are in advanced clinical trials.

Razumab, developed by Intas Pharmaceuticals, is a ranibizumab biosimilar approved in India in 2015. A battery of clinical trials demonstrated high similarity in efficacy and safety to the reference product, but it ran into quality difficulties early, with variations noted between batches. The cause was determined to be higher endotoxin levels in the buffer used during manufacturing, and the problem was resolved, the authors said.

Pharmacovigilance, quality control, and monitoring are extremely important, along with immunogenicity testing before market approval.

Other ranibizumab biosimilar candidates include:

FYB201 (Formycon and Bioeq, Germany), for which satisfactory phase 3 clinical results have been reported;

Xlucane (Xbrane Biopharma, Sweden), which the authors said may be produced with better technology than the reference drug and has reached the phase 3 clinical stage of development;

R-TPR-024/Ranizurel (Reliance Life Sciences, India), which was approved by Indian regulators in 2020;

SJP-0133/GBS-007 (Senju Pharmaceutical, Japan), in phase 3 trial development;

LUBT010 (Lupin, India), under phase 3 development; and,

CKD-701 (Chong Kun Dang, Republic of Korea), also under phase 3 development.

Many bevacizumab biosimilars are already approved and on global markets. In the United States, Avastin, the reference product, is used off label for eye treatment and requires pharmacy compounding for this purpose. So far, bevacizumab has been cheaper to use for eye disease than ranibizumab, but the development of a bevacizumab biosimilar specifically for eye disease could change the pricing dynamics, the authors wrote. In many countries, pharmaceutical compounding services are not readily available, they note.

Outlook Therapeutics is developing ONS-5010, which has been accepted by the FDA for review in the form of an investigational new drug application, not specifically a biosimilar biologics license application. A phase 3 trial in patients with neovascular AMD is underway, and “if the intravitreal formulation is approved, the justification for the use of a compounded version [of bevacizumab] may no longer exist. However, it may lead to a paradoxical rise in the cost of bevacizumab in ophthalmology,” the authors wrote. 

Multiple aflibercept biosimilars are under development. These include:

MYL-1701P (Momenta Pharmaceuticals and Mylan, United States), and the manufacturers anticipate FDA approval and a launch in 2022 and 2023, respectively;

ABP 938 (Amgen, United States), in phase 3 development;

FYB203 (Formycon and Bioeq, Germany), also in phase 3 clinical development, with target US and EU market introduction in 2023 and 2025, respectively.

SB-15 (Samsung Bioepis, Republic of Korea), which began phase 3 clinical trials in June 2020;

SOK583A19 (Sandoz, Switzerland), in phase 3 development;

CT-P42 (Celltrion, Republic of Korea), also in phase 3 clinical development;

ALT-L9 (Alteogen, Repubic of Korea), which has not yet begun phase 1 trials; and,

OT-702 (Ocumension Therapeutics and Shandong Boan Biological Technology, China), in phase 3 trials.

With many ophthalmology biosimilars likely to reach market in the next several years, “pharmacovigilance, quality control, and monitoring are extremely important, along with immunogenicity testing before market approval,” the authors concluded.

Kapur M, Nirula S, Naik MP. Future of anti-VEGF: biosimilars and biobetters. 

. 2022;9:2. doi:10.1186/s40942-021-00343-3

Biobetters may gain an edge on reference products, and multiple biosimilars are under development for ophthalmic disorders, the authors write. 

Review: Biobetters and Biosimilars Set to Emerge in Ophthalmology

Seeking to position themselves optimally for a share of the adalimumab (Humira) market, Samsung Bioepis and Organon are seeking FDA approval for a biosimilar high-concentration, citrate-free formulation (100 mg/mL) of adalimumab.

Adalimumab is an immunosuppressive drug for rheumatologic and gastrointestinal disorders. It is used for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, Crohn disease, and ulcerative colitis.

The market for high-concentration adalimumab is said to be increasing in both the United States and the European Union, as its citrate-free aspect reduces pain upon injection. Citrate is a buffer that helps to stabilize pH, but it is known to cause patients intense discomfort and affect patient adherence to adalimumab. 

The high-concentration, low-volume formulation also adds convenience during administration.

In the United States, high-concentration adalimumab represents about 80% of the total market for this agent, based on recent IQVIA Midas data. 

Samsung Bioepis is the biosimilar developer in the partnership with Organon, which has helped to commercialize multiple Samsung Bioepis biosimilars so far. Organon would be the US marketing partner.

The adalimumab high-concentration biosimilar candidate is based on a lower-concentration biosimilar (SB5, Hadlima; 50 mg/mL) that was approved by the FDA in 2019.

Currently, adalimumab biosimilars are available in Canada and the European Union, but have not been able to penetrate the US market because of exclusivity protections for Humira. Hadlima’s anticipated US launch is June 2023, six months after the anticipated entry of the first adalimumab biosimilar, Amjevita (Amgen), in January 2023.

In a statement, Samsung Bioepis and Organon said the application for high-concentration Hadlima has been accepted for review by the FDA. The companies said their biologics license application was submitted to the FDA in October 2021. They are targeting a US launch on or after July 1, 2023.

The application was based on data from a randomized study comparing the pharmacokinetics, safety, tolerability, and immunogenicity of 2 formulations of SB5 (100 mg/mL vs 50 mg/mL) in healthy volunteers.

The submission of a fresh application for Hadlima reflects the competitive positioning of companies as the biosimilar entry point begins. In October, Boehringer Ingelheim obtained interchangeable status for its Cyltezo adalimumab biosimilar. Cyltezo was approved in lower-concentration, 20 mg/0.4mL and 40 mg/0.8 mL prefilled syringes, and the company has (thus far unsuccessfully) sought flexibility from the FDA on the product strength allowances, presumably so it can offer a high-concentration formulation without undergoing a repeat biologics license application.

However, the interchangeable designation is potentially of competitive value, as it allows pharmacists and health care institutions greater flexibility in dispensing lower-cost biosimilars rather than higher-cost reference drugs.

Thus far in the United States, no high-concentration adalimumab biosimilars have been approved by the FDA. Among the companies seeking approval for high-concentration adalimumab biosimilars are Teva/Alvotech (AVT-02), Celltrion (CT-P17), and Amgen (ABP-501 HC).

All of the approved adalimumab biosimilars are low concentration, some are citrate free, and some are latex free. Needle size, also a potential product differentiator, also varies among approved products.

In December, the list of adalimumab biosimilars approved for marketing numbered 7, augmented most recently by an FDA green light for 

(40 mg, subcutaneous), a Coherus BioSciences product.

The companies hope to gain FDA approval for a high-concentration, citrate-free version of Hadlima, an adalimumab biosimilar that was approved in a lower concentration in July 2019.