Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Some countries in Europe may have opened the door to biosimilars in only a token way, simply to tempt price reductions from originator companies. Others just haven't opened the door wide for enough biosimilar competitors to enter. However, these situations may slowly be changing as a result of lobbying by Medicines for Europe, a trade association whose members interviewed with The Center for Biosimilars

In Part 2 of this interview with Adrian van den Hoven, director general of Medicines for Europe, and Diogo Piedade, market access manager for Medicines for Europe, we continue our discussion of the competitive dynamics of biosimilar markets in the European Union.

Van den Hoven and Piedade explain the importance of having robust competition among biosimilar producers in a single marketplace. They contend that money saved via biosimilars makes more money available for complex medical treatments, and they discuss efforts by Medicines for Europe to persuade countries to move away from single tender systems that grant one biosimilar preferred status and, in the process, discourage manufacturers of other biosimilars from competing.

CfB: Please explain the connection between the number of biosimilar companies able to compete in a European market and patient access to biosimilars?

 There's a correlation between how much uptake there is in the market and how many companies can play in the market at the same time. In some markets our companies have really struggled to get market share, like Ireland, or historically, Belgium, although that's changing. Now, Belgium is stimulating more biosimilar competition, but historically, Belgium, Ireland, Malta, these were countries that basically wanted to use biosimilars just to lower the price of the reference product, but not to actually use biosimilars. Of course, for biosimilar companies, that's not a really attractive market for them, so they started exiting those markets, and now some of them are reforming like, definitely Belgium is putting in measures to stimulate the use of biosimilars. Biosimilars actually have to be used, otherwise you're not going to sustain competition in the market. And that competition is what lowers the prices and enables you to give access to more patients or to reinvest the money elsewhere, whatever you're looking to do as a government.

CfB: Biosimilars bring lower costs, especially multiple biosimilars, so what effect does this have on innovator companies and their willingness to invest in these markets? 

 In markets that have biosimilar competition, it's actually positive for innovation, because you give access, let's say bigger access to the biological therapy, but then newer therapies can also come into the market because there's some room in the budget for that. A good example is psoriasis, where you have the launch of at least 2 or 3 new biologics. For sure, that's partly sustainable due to the biosimilar competition in monoclonal antibodies. And so, there is innovation going on. And without the competition driver for the price savings, that would be very hard to sustain in Europe, because the biologics budgets, like in the United States, are going up. So, I think it is a driver. Of course, what it also means is the originator drug faces a lot of losses in Europe, typically. Herceptin or Humira have faced some pretty brutal competition from biosimilars in Europe, but they've benefited from close to 16 years of monopoly before that, and they have earned their return on investment. So, I think that's fair.

You also see examples of biosimilars enabling certain originator medicines to be used. I can think of 1 specific case where an originator medicine was not being used in the United Kingdom, because it was used in a [very costly] combination with another product, and when that second product became a biosimilar, then [the National Institute for Health and Care Excellence] reviewed their recommendations and said, Well, now that you have a biosimilar, this combination treatment makes sense from a pharmacoeconomic perspective. So, biosimilars are acting as enablers.

 I would add that this combination approach is the tendency in Europe, at least for the originator industry, so as parts of combinations become biosimilars, you will dramatically reduce the overall cost of the combination. This is one of the dynamic effects of competition—it actually is one of the drivers of innovation, at least in the European context.

CfB: Are policymakers in European markets more fond of the single-tender system than biosimilar developers?

 It depends on what you mean by policymaker. With regard to certain payers, yes. Their key performance indicator is how much have I saved with this biosimilar? and they report to their bosses who, in one way or another, are the ministries of health in Europe, in the different countries, and so they say, “Well, we save so much by using biosimilars,” and “Isn't it fantastic?!” and they get patted on the back. However, some of the payers are starting to realize that's not ideal if the biosimilar players who didn't win the tender start exiting the market. And that's where we see changes, like in the United Kingdom or in Denmark, where they're starting to say “Maybe I can run a victory lap this year, but next year I might not do so well. So, it's better for me to reconsider these models.”

We’re having conversations with some of those players, and they're not embracing this totally, but they're open to consider it and to start to move. Diogo has had very in-depth conversations with the Danish central purchasing authority, if you wish. And they have not done exactly what we wanted, but they have changed their approach toward tenders.

Another thing that's happening in Europe is that in the hospital setting, there's more and more of a realization that tender models have an impact on how many companies are willing to participate in the market, and eventually, with older generics, at least, this can create out-of-stock situations, or even worse. I think this is really sinking in now, as well. It's forcing payers to rethink this. I think if you speak to the ministries of health, they're much more on board with this thinking—even the German regulatory authority [Federal Institute for Pharmaceuticals and Medical Products, BfArM]. That’s the regulatory authority for chemical products, not for biological products; but nevertheless, it even has on its website recommendations that hospital tenders in Germany should follow certain rules, like have multiple winners. So, it's slowly percolating and changing over time, but there's still some work to do. And there is still some opposition, for sure, from some of the payers in particular.

 In terms of an increase in the number of tender winners, definitely, it’s something we’re starting to see. Also, we’re not talking about price as the sole criterion for awarding the tender. That’s also a direction we’re slowly moving toward. And we, as biosimilar players, also acknowledged that a race to the bottom does not create healthy competition over the long term.

CfB: Did you not see a need to create a scorecard for every country in Europe?

 We would have liked to have done all the countries, but even going to this level of detail for 12 countries was a pretty intense level of activity. The other thing is, biosimilar policies are a little bit in motion. So, countries that are not succeeding with biosimilar uptake are obviously starting to introduce changes and learn from the others and contacting us—“How do we do this, etc.” So, as you work on one of these reports, it's a kind of moving target as well, and so it would have been a pretty heavy exercise to go after all of the countries. I think what we capture here is the majority of the market and a good subset of case studies. If you take all of these countries combined, you can more or less apply the different models to the other markets, because there are some similarities.

 What we did was obviously we went for the top 5 EU countries. We chose the Nordics because they are regarded as leaders in biosimilars, and we wanted to take a deeper look and see what can be improved from their experience. We also looked at Eastern Europe, an area where we know they have quite a challenging landscape in terms of patient access, still. And then we looked at the Netherlands, which has a bit of a different system and a different model compared with all the others. So, we tried to capture, if you will, different major groups within Europe to give a good understanding of how the policies play a role there.

Articles

Although more advanced than in the United States, biosimilars markets in Europe may discourage competition over the long term, said officials from Medicines for Europe.

Interview: EU Biosimilars Markets Lack Competition

Biopharma revenue climbed for Pfizer in the second quarter of this year, although revenue dipped for Enbrel, the etanercept reference product for rheumatoid arthritis.

Pfizer holds rights to distribute Enbrel in Europe as well as other markets outside the United States where patents on the drug have expired and it faces biosimilar competition, such as in Japan and Brazil.

Without providing an exact dollar figure, the company said operational 

 for Enbrel were down 16%. Overall, 2020 second-quarter biopharma revenues were $9.8 billion, up 4% from $9.4 billion in the second quarter of 2019.

Amgen holds rights to distribute Enbrel in the US market, where patent protections remain in force and competition is not anticipated before 2029. Most recently, Amgen secured its Enbrel foothold in the United States with a court ruling that rebuffed attempts by Sandoz to invalidate Enbrel patents.

Sandoz and Samsung Bioepis both have FDA approvals to market biosimilar versions of etanercept but have been restrained by Enbrel's exclusivity rights. Both have 

During the quarter just ended, Pfizer gained FDA approval for pegfilgrastim biosimilar Nyvepria, which references Neulasta. Pegfilgrastim is indicated for controlling infection related to febrile neutropenia in patients receiving chemotherapy.

A 2020 launch is anticipated for Nyvepria, although an exact date has not been announced.

In its financial guidance, Pfizer said that competition from generic and biosimilar products will have an overall negative affect on revenues of $2.4 billion in 2020, based on an assessment of Pfizer products that have recently lost or are expected to lose patent protection.

In sum, Pfizer reported second-quarter 2020 revenues of $11.8 billion, down 11% from $13.3 billion in 2019.

The company said the pandemic has not significantly affected its supply chain, and it has scaled up its manufacturing operations to supply a potential novel treatment or vaccine for coronavirus disease 2019.

Like many others, Pfizer paused its clinical trial recruitments in the early months of the pandemic, but it has since restarted enrollment across its drug development portfolio and begun new studies, utilizing remote monitoring and careful coordination with clinical trial sites to accommodate safety needs amid the virus outbreak.

The company said that its sales personnel were able to meet in-person with doctors for nearly the entire second quarter in international markets, whereas this was not possible for most of the 3-month financial reporting period in the United States.

While Amgen fends off etanercept biosimilar competition in the United States, Pfizer said it is facing a mounting battle against biosimilar competition in European and other markets.

Pfizer Reports Continued Weakness for Enbrel in Europe

 marketing authorization for the first subcutaneous (SC) formulation of infliximab, Remsima SC, for an additional 5 indications, including inflammatory bowel disease and ankylosing spondylitis.

This means the product indications now match all approved indications for the intravenous (IV) formulation in adult patients, including ankylosing spondylitis, Crohn disease (CD), ulcerative colitis (UC), psoriatic arthritis, and psoriasis.

The EC marketing authorization is based on positive 

 comparing pharmacokinetics, efficacy and safety of the IV and SC formulations of Remsima in patients with CD and UC.

Based on the results of a 1-year study, a 120 mg fixed dose of Remsima SC has been approved for use in the European Union, in adults regardless of body weight, in both existing and newly added indications.

“We are pleased to announce this important regulatory milestone earlier than we expected, with the European Commission prioritizing review of this important new administration option,” said Hyoung-Ki Kim, vice chairman at Celltrion Healthcare, based in Incheon, Republic of Korea.

The approval comes after a positive opinion for Remsima SC from the Committee for Medicinal Products for Human Use of the European Medicines Agency in June.

Kim said the regulatory approval came earlier than expected and followed prioritization of the review by the European Commission.

“Today’s approval marks an important progress for the gastroenterology community as it means that treatment can now be administered in significantly less time, thereby providing patients more flexibility and control over how they receive their treatment,” said Stefan Schreiber, MD, PhD, director of the Clinic for Internal Medicine at Kiel Campus of the University Hospital Schleswig-Holstein in Germany.

Additional indications for Remsima SC, an infliximab biosimilar, are approved by the European Commission (EC).

Celltrion's Subcutaneous Infliximab Gains EC Nod for 5 Indications

Biosimilar competition doesn’t happen on its own. It requires incentives and a competitive market structure to keep biosimilar manufacturers interested in participating. The winner-take-all tender system in Europe, which allows a single biosimilar to gain preferred status, has the undesired effect of causing unsuccessful competitors to drop out of the bidding process in ensuing years.

These were some of the conclusions officials from the trade association Medicines for Europe reached in a country-by-country analysis of biosimilar success in Europe.

 that evaluated policies and progress as measured by biosimilar competition, price reductions, and overall increase in use of drugs for which biosimilars are available. The report was done in partnership with the IQVIA institute for Human Data Science.

 (CfB) spoke with Adrian van den Hoven, director general of Medicines for Europe, and Diogo Piedade, market access manager for Medicines for Europe, about their observations.

In Part 1 of this interview, van den Hoven and Piedade explain why a deep dive into the biosimilar market development in Europe was needed. They describe how this knowledge can improve patient access through introduction of policy change and a competitive framework for biosimilars introduction, and they describe the importance of a sustainable system.

Van den Hoven and Piedade also discuss national examples of biosimilar market success from Poland, which has struggled, and Norway, which has done well but does not have uniform access between hospitals and clinics. And they provide thoughts on the introduction of a multi-tender system that would keep biosimilar companies interested in staying in the marketplace even if they do not win preferred status.

For reference, the scorecard report produced by Medicines for Europe and IQVIA can be accessed 

CfB: What led you to put this report together?

The European [biosimilar] market has been under development for [many] years now, and so there have been growth in some areas and difficulties in other areas. We really wanted to do an assessment of which policies were having a positive benefit in terms of patient access to biologics, and which ones were having less of a benefit. We also tried to look at it from the perspective of how sustainable the market would be over time.

We've done a few reports before, but we've never gone this deep into the specific measures to see how effective they are, what are the benefits of the different policy tools that can be put into place, and what is the interconnection between different policy measures applied together, to make it work in practice and adapt it to slightly different situations in each European country. We have a so-called single market in Europe, but we have different pricing and reimbursement systems, ultimately.

Whenever you look into these policy aspects, it can get very technical and very heavy, very quickly, so we wanted to create a tool that acts as a conversation starter. So, at glance, you can quickly look at one of the scorecards for one of the 12 countries and know the areas where policy improvements can be made and the areas where, in terms of biosimilar policy, that country is faring better or not so good.

CfB: Who do you think is going to benefit most from this report?

We hope that first of all patients are going to benefit, because one of the challenges we still have in in Europe is that when you don't have a lot of competition from biosimilars, you still have a lot of restrictions to access because of the cost. There are essentially a lot of hidden restrictions in the European system. We hope that these policy tools can help different policymakers introduce a better system that will increase biosimilar utilization and remove some of the restrictions to access the biologics in general.

A lot of people think about Europe that because we have subsidized state health care, that somehow means you have no access issues. Unfortunately, it's not the case. We do have restrictions, notably for biologics, not just in Eastern Europe, which is less affluent, but also in Western Europe. But I think for us, that's the first target.

We took a broad look at biosimilar sustainability with this report. We want to make sure that sustainability means that it's sustainable for all the stakeholders involved. That also encompasses the health care systems, the prescribers. We also hope to bring more prescriber options to the table and to the health care systems, with increased efficiency. We also hope that these points are taken in by policymakers, and they are the ones that should be enacting the changes that we are advocating for here.

CfB: So, what have you learned about the progress of biosimilars in Europe and in particular European countries? 

I think one of the key lessons to learn here is that biosimilars competition doesn't happen on its own. You need measures to stimulate the competition, to encourage use by stakeholders—physicians, principally, because they are the prescriber, and they may choose to prescribe the biosimilar or the reference product. And so certainly without stimulus, there will be no competition. You can see that wherever you don't create a competitive playing field, there is almost no uptake. A good example of that is insulins, where there's very limited biosimilar uptake, because there are effectively very few measures to encourage competition in that space. In Western Europe, at least in the field of oncology, you see a massive uptake in the use of biosimilars, because there are a lot of measures to support competition.

What was interesting to find as well was that the countries that have a more intentional policy framework, a willingness to adopt and to make the most out of the benefits of biosimilars, are the countries that are able to expand access. And then it's very clear, as well, that those countries where policies are not so well defined or they do not support the use of biosimilars, then you see them lagging compared with other countries in terms of access.

CfB: Can you give us some examples of markets that are ahead or behind?  

I can point out one country where I'd like to see some action. That's definitely Poland. I previously mentioned oncology biosimilars. And in Poland, they have very heavy restrictions on expensive medicines. This is to obviously control the budget, but what it means is that you have an incredibly low access to biologic treatments like trastuzumab, and we've seen that although they have biosimilar uptake or biosimilar competition, they haven't removed the restrictions to access. So, basically the government has lower prices, but it doesn't have higher use. And this is really a sad situation, because the level of access is so low that it really means a lot of patients are not getting the correct treatment. So, something I'd really like to see is that in countries where biosimilars definitely have a price-lowering effect on the market, they give those benefits back to the patients in terms of expanded use to deal with those access issues.

Poland is a good example. What is interesting as well is that even those countries where you would assume that the biosimilar framework is fully functioning or it's faring better, even those have points in need of improvement.

Norway is frequently regarded as one of the champions, but despite having good biosimilar uptake in the hospital setting, they still lag in the clinic setting. And then you have for other European countries quite a similar picture, where what is interesting and striking is that depending on the national context you'll see very different recommendations from one scorecard to the other, from one country to the other, because the policy framework and the different interplay between the national framework and the policies implemented will have different recommendations and points for improvement.

In some European countries, we have a form of national hospital tendering, where an entity buys on behalf of the hospitals, and those systems have been pretty effective to generate a high level of competition, even up to a 100% market share for the biosimilar, and pretty positive to stimulate biosimilar competition.

The downside with those systems is that if you are not the winner of the tender, you have a tendency to want to exit that market altogether and not participate in, let's say, the tender the next year. And over time, what that leads to is a reduction in the number of companies that want to want to participate in the different markets. We're starting to see now some experiments with countries or systems trying to introduce multi-winner tenders, so that the lowest bidder gets a bigger market share and a bigger benefit, but the next one down can also participate in the market. We're seeing this being toyed with or experimented with in Denmark, in the United Kingdom. We think those are good initiatives because we still believe that even after you have biosimilar competition, keeping competitors in the market and keeping a healthy competitive market is a good thing. That healthy competition will keep the market at bay over the long term. You may not get a dramatic, short-term win, but you'll get a definite medium-term gain by having sustained competition.

The Center for Biosimilars® (CfB) spoke with Adrian van den Hoven, director general of Medicines for Europe, and Diogo Piedade, market access manager for Medicines for Europe, about their scorecard report for biosimilar access in European markets.
 

Interview: Medicines for Europe Reports on EU Biosimilar Success

Topping a productive period, Biocon said its total revenues for the fiscal first quarter came to $225.8 million, up 14% driven by growth in its biosimilars and generics business units, which the company said grew 19% and 16%, respectively.

Net profit was $20.4 million. The company’s research services business experienced flat revenue of $56.4 million, which the company attributed to a slowdown caused by the coronavirus disease 2019 (COVID-19) pandemic.

“It has been a breakthrough quarter for Biocon as we made a significant contribution to the global efforts aimed at addressing the pandemic through our innovative science,” the company said in a 

During the quarter, the company received FDA 

 for its insulin glargine (Semglee), the third product resulting from its collaboration with Mylan to be approved in the United States.

Biocon partner Mylan, meanwhile, received FDA approval for a biosimilar adalimumab (Hulio), for which Biocon has a shared economic stake.

Biocon also received a certificate of Good Manufacturing Practice from the European Medicines Agency for its drug manufacturing facility at Biocon Park in Bengaluru, India.

Biosimilars revenue for the just-ended quarter was $92.5 million, up from $77.8 million in the comparable, year-ago quarter. Biocon estimated that the number of patients who used the company’s biosimilars totaled 2.9 million in the just-ended quarter.

It said the growth reported for this business period was derived from strong sales across most of its global markets along with steady sales in the United States and Europe, “aided by a spillover of revenues from the previous quarter.”

The company said it anticipated further growth based on demand in Latin America and the Commonwealth of Independent States, which include 12 former Soviet republics (Russia, Armenia, Belarus, Kazakhastan, etc).

“We have started [fiscal year 2021] on a very strong note,” said Christiane Hamacher, CEO and managing director of Biocon Biologics India, the biosimilars arm of Biocon. She said sequential growth from the fourth quarter of the previous fiscal year to this quarter was 60%.

Among the company’s recent achievements was its deal with Voluntis to market the digital titration device Insulia for patients receiving basal insulin products. The company believes Insulia has strong potential to gain a business hold during the COVID-19 crisis because of the need for patients to be able to self-manage their care from their homes. Via Insulia, patient medication can also be monitored by health care workers remotely.

Biocon has 3 FDA-approved biosimilars. It hopes to launch an etanercept biosimilar in Europe later this year.

The company said its biosimilar pegfilgrastim (Fulphila), codeveloped with Mylan, has held onto its market share in the United States “despite increasingly competitive dynamics.” It did not disclose that market share. During the just-ended quarter, the product was launched in several European markets.

Ogivri, a trastuzumab biosimilar, is also a Biocon/Mylan collaboration that the company said has seen “a positive trend in market share” in the United States.

The company has a bevacizumab biosimilar candidate that is under FDA and EMA review currently.

In addition, the company is working with the FDA on a 351(k) application to bring a recombinant human insulin (rh-insulin) to the market as a biosimilar. Biocon also is working with Mylan on the development of a biosimilar insulin aspart.

“We target to have at least 8 of our biosimilars available in developed markets through our partner by the end of fiscal year 2022,” the company said in its statement. Those are trastuzumab, pegfilgrastim, adalimumab, bevacizumab, etanercept, insulin glargine, insulin aspart, and rh-insulin.”

Biocon has recently stated it intends to take its biosimilars unit 

For Biocon, overall revenues were up during the fiscal quarter that just ended, driven by strong revenues in its biosimilars and generics operations.

Biocon Reports Strong Quarter for Its Biosimilars Unit

In the second quarter of 2020, net revenues climbed slightly for Biogen, of Cambridge, Massachusetts, although its biosimilar revenues declined somewhat amid the coronavirus disease 2019 (COVID-19)—challenged marketplace. Overall revenues climbed to $3.68 billion from $3.62 billion, according to the company's earnings 

Biosimilar revenues were $172 million, down 7% in the second quarter compared with the same period in 2019. The decline came despite efforts to extend commercialization agreements and earnings improvement 

Earlier this week, the company announced the 

 of strategic finance and operations specialist Michael McDonnell as executive vice president and chief financial officer, effective August 15, 2020. McDonnell currently is executive vice president and chief financial officer at IQVIA, a data and technology leader in the health care field.

The etanercept biosimilar Benepali brought in $106 million in the second quarter compared with $120 million a year earlier, a 12% decline and off 20% from the first quarter of this year.

Biogen’s adalimumab product Imraldi notched sales of $45 million, down 5% from $47 million a year ago, and down 27% from the first quarter of 2020.

The company’s infliximab biosimilar (Flixabi) saw sales climb to $21 million from $17 million in the year earlier quarter, a gain of 23%. However, sales of this product were down 13% from the first quarter of the year.

Biogen, which specializes in the neurosciences, saw some increases in its multiple sclerosis fumarate product revenue. Fumarate medication helps to improve iron deficiency—related anemia. Overall, multiple sclerosis product revenues dropped 2% quarter over quarter.

Revenues from dimethyl fumarate (Tecfidera) climbed to $1.18 billion from $1.15 billion a year ago; and sales of diroximel fumarate (Vumerity) were $9 million in the quarter just ended. The product was launched late last year at a controversial price of $88,000 for a year’s treatment.

In revenue guidance for the full year 2020, the company anticipated $13.8 billion to $14.2 billion versus its previous guidance of $14.0 billion to $14.3 billion.

Amid the COVID-19 pandemic, the company noted that supply channel inventory levels of its multiple sclerosis products increased by a value of $10 million during the second quarter, versus declines of $30 million in the second quarter of 2019 and $115 million in the first quarter of 2020.

The company saw a 7% decline in biosimilar revenues in the second quarter of 2020 compared with the same quarter in 2019.
 

Biogen Biosimilar Revenues Dip Amid COVID-19 Pandemic

Two executives at Sandoz and Boehringer Ingelheim, both biosimilars companies, have taken aim at what they call disparaging information about biosimilars that weakens provider and patient trust in these lower-cost products and slows uptake and access.

In an opinion article published in the biologic therapies journal 

, Hillel P. Cohen, PhD, executive director of scientific affairs for Sandoz, and Dorothy McCabe, PhD, FCP, executive director at Boehringer Ingelheim, contended that public willingness to accept biosimilars is undermined in numerous ways by how these drugs are referenced in literature and clinical practice.

“Biosimilars are not well understood by many health care professionals and patients. The knowledge gap is exacerbated by disparagement of biosimilars and dissemination of misinformation, whether intentional or otherwise,” they wrote in their coauthored analysis.

Both Cohen and McCabe are members of the education committee for the Biosimilars Forum, a biosimilar promotion collaborative whose membership includes 9 of the largest biosimiliar producers, including Biogen, Coherus BioSciences, Merck and Co, Pfizer, Fresenius Kabi SwissBioSim, Teva, and Samsung Bioepis.

The issue of biosimilar characterization is a hot button currently. In a 

 early this year, the FDA and Federal Trade Commission pledged to work harder to combat what they described as deliberately misleading literature and descriptions of biosimilars that amounted to anticompetitive behavior by companies that market the original drugs upon which biosimilars are based.

 that compared biosimilar filgrastims in an unfavorable light with the originator product, Neupogen, drew heavy fire from European biosimilar development consultants who contended the study stood on a very weak scientific platform and overlooked much accumulated evidence in support of biosimilar safety and efficacy.

The disparaging way biosimilars are often characterized does not allow them to compete on a fair basis with originator products, Cohen and McCabe wrote. This mischaracterization is directly counter to positions on biosimilar quality and value espoused by the regulators that approve them, they added.

Sometimes the fault is not in any intentional mischaracterization, but in the common terminology for biosimilars, according to Cohen and McCabe. The term “biosimilar” implies “a difference of some sort,” and the “abbreviated licensure pathway” used to approve biosimilars in the United States suggests that the approval process is “less rigorous or ‘more relaxed,’” they wrote.  

Similarly, the concept of “nonmedical switching” is used to describe transitioning patients from a reference product to a biosimilar, when in fact the medical process has not been suspended. The patient is actually continuing the same treatment but with a different brand, Cohen and McCabe argued.

They observed that when it comes to clinical data, the requirements for biosimilar approvals are somewhat different. Biosimilar developers need to establish equivalence to the reference product using "analytical analysis as the foundation and clinical safety and efficacy studies…as needed.” This is vastly different from the requirement for phase 3 safety and efficacy studies for each indication for an originator biologic.

The problem is that health care practitioners may tend to expect the same type of data to be available on biosimilars as for originator products, Cohen and McCabe wrote. “While the clinical data package supporting biosimilar approval is more streamlined compared to the reference product, the overall data package is equally rigorous.”

Similarly, approved biosimilars can be used in all the settings indicated for the originator drugs without the need for studies in each indication. “Extrapolation of indications is based on structural and functional similarity and [pharmacokinetic/pharmacodynamic] data, and not between the indications of the reference product,” they wrote.

Beyond misleading language and misconceptions, in Europe inaccurate claims have been made about the reliability of pharmacovigilance monitoring of biosimilars, and it is often incorrectly stated that interchangeability is a higher standard for biosimilar approval than biosimilarity, Cohen and McCabe contended.

“The quality standards for biosimilars and interchangeable biologics are absolutely identical,” and although an interchangeable stamp would allow a pharmacist to substitute a biosimilar without consulting the physician, physicians are perfectly free to switch between reference products and biosimilars even if the biosimilar does not have interchangeable status, they noted.

Providers can help support biosimilar use simply by employing body language that expresses confidence in these products or by choosing their words carefully to avoid framing biosimilars in a negative way, the authors wrote.

Doctors, too, are influenced by wording more than they may realize. “This was quantified in a survey that reported that 60% of EU physicians were either very comfortable or comfortable in switching of stable patients to biosimilars, but when the very same question was posed with the phrase 'non-medical switching' inserted, the percentage declined to 42%,” Cohen and McCabe wrote.

With patient access to more affordable medicine at stake, biosimilar advocates must be vigilant, they concluded. “Biosimilar disparagement and misinformation will continue unless it is challenged; we cannot ignore these activities. It is the responsibility of all stakeholders to challenge biosimilar disparagement and misinformation when encountered.”

Cohen HP, McCabe D. The importance of countering biosimilar disparagement and misinformation. 

. Published online July 20, 2020. doi:10.1007/s40259-020-00433-y

Biosimilar misinformation takes many forms, some of it institutionalized in the form of word usage and some of it deliberately disparaging, 2 executives of Sandoz and Boehringer Ingelheim contend.
 

Sandoz, Boehringer Ingelheim Battle Biosimilar Misinformation

Biocon Biologics, specializing in biosimilars and insulin, said it has teamed up with Voluntis, a digital products health care company, to market an FDA-approved product that provides automated insulin dose recommendations to help individuals with diabetes self-manage their condition.

The product, Insulia, also enables health care teams to monitor by remote. It will be marketed to patients with type 2 diabetes using Biocon Biologics—brand insulins, which include recombinant human insulin, insulin glargine, and insulin aspart.

Under terms of the agreement, Biocon will distribute the product in several markets worldwide.

The company said Insulia is the first digital therapeutic with regulatory approval for providing automated titration recommendations for basal insulins. Insulia also has CE (Conformité Européenne) marking, meaning that it conforms to European Economic Area manufacturing standards.

“The demand for at-home treatment and telemedicine solutions is dramatically increasing around the world,” Biocon said in a 

“We believe pairing our products with a digital therapeutic solution will help improve patient outcomes and reduce costs to health care systems in the long term. We remain committed to impact patients’ lives through innovative solutions,” said Christiane Hamacher, CEO and managing director of Biocon.

Earlier this year, Biocon's parent company, Biocon Limited, announced plans to take the biosimilars unit 

 in an initial public offering of yet-undetermined valuation.

In a deal with Voluntis, Biocon Biologics aims to extend the appeal of its insulin products by offering a digital titration device for self-management of insulin dosage.
 

Biocon Biologics Pairs Digital Therapeutics With Insulin

Several trastuzumab biosimilars have been launched this year, and 6 FDA-approved adalimumab biosimilars are lined up for launch in 2023, but such a cornucopia of lower-cost medicine is not looked upon as favorably as might be expected.

The reason? Payer policies make it difficult for providers to use the lowest-cost biosimilars available. In a webinar hosted this week by MJH Life Sciences™, a panel of experts discussed how industry dealmaking is affecting treatment decisions and use of resources at the provider level.

FDA-approved biosimilars are not different from reference products in any clinically meaningful way, but in the business world, a payer may put a particular biosimilar on formulary because of the rebate deal it got from the manufacturer or high-pressure sales tactics used by a rival drug producer. This means that providers often have to use the biosimilar that the payer wants them to use—not the lowest-cost drug. For practices that work with multiple payers, each with different biosimilar preferences, this can be “a nightmare,” panelists said.

The Difficulty of Stocking Multiple Biosimilars

Stocking multiple biosimilar brands to satisfy the preferences of multiple payers is costly, and ensuring that payer preferences are followed requires the use of controls and staff interventions that would not ordinarily be needed for treatment decisions.

“There’s a lot of work by nurses, pharmacists, and finance people to transition to biosimilars,” said panelist Ali McBride, PharmD, MS, BCOP, FASHP, FAzPA, clinical coordinator of hematology/oncology for The University of Arizona Cancer Center in Tucson.

 for a practice that uses the wrong biosimilar brand and cannot get reimbursed for it, said Kathy Oubre, MS, a panelist who serves as chief operations officer for Pontchartrain Cancer Center, which has clinic locations in Covington and Hammond, Louisiana. Her practice has implemented a signoff procedure to ensure that the preferred drug is given to a patient.

“Payers are really taking an active stand in dictating the drugs we use,” she said. Payer preferences make it difficult for a practice the size of Pontchartrain to provide biosimilars to patients. “It presents a lot of operational challenges.”

Given his druthers, McBride said, payers would not 

 what biosimilars could be used. The United States would follow a European-style model in which the preferred or recommended biosimilar is the lowest-cost biosimilar available. In Denmark, for example, a biosimilar company will win a tender to provide a biosimilar for a 12-month period, after which the bidding process will reopen.

This not only lowers costs, McBride said, but also shortens the amount of time needed to transition a patient to a biosimilar. In the United States the process of getting a patient set up with a biosimilar is much more complicated on many levels. “We’re constantly working to address these pieces,” McBride said. He added that achieving of biosimilar access equality, or “parity,” across drug brands is crucial to realizing the true promise of biosimilars. “I would love to see more of a European model,” he said.

“Parity would be great,” Oubre agreed. “We believe in the science of biosimilars and the cost savings, and at the end of the day we all know that term 

Kaiser Permanente is a combination payer and medical group conglomerate that has, through its leverage, been able to achieve very high levels of biosimilar uptake, specifically by singling out a single biosimilar for coverage in different classes of medicine. “Kaiser has a unique structure,” said panelist Timothy J. Chiu, PharmD, the pharmacist evidence analyst and strategist for hematology/oncology at Kaiser Permanente. “We have tried to focus on 1 product; it reduces operational challenges,” he said.

He acknowledged that at the provider level there are complexities that affect whether patients can receive the lowest-cost biosimilar, but said that Kaiser Permanente has worked to overcome these issues.

However, the emphasis on a single biosimilar makes it simpler to achieve large-scale buy-in, he added. There’s an education component to building confidence among providers and patients that can be accomplished with a streamlined approach. “There are still a lot of misconceptions about biosimilars and people are uncomfortable about switching despite all the data,” Chiu said.

Practices attempt to discuss biosimilar choices with payers so that restrictions can be relaxed. This is not always a successful process. McBride described “a lot of pushback” from payers, and Oubre said that in her experience, “some are more receptive, some are not.”

With regard to the education component, McBride said that biosimilar education itself has to be defined. This could take many forms. For example, providers and patients would benefit from more real-world information about biosimilars as well as further studies, particularly ones that would elucidate the value of switching from originator drugs to biosimilars in order to extend the benefits of therapy. “We need more data to have this discussion,” he said.

Good pharmacovigilance will be an important way to add to this critical information pool, Chiu added.

Education could include information about oncology models of care, such as Oncology Care First, the CMS successor to the Oncology Care Model, McBride said. It’s important to know how biosimilars are going to help achieve the savings that these models are supposed to achieve, he said.

Kaiser Permanente has sought to give providers educational materials on biosimilars, and these materials have included clinical data on individual biosimilars investigated in particular settings. This has helped to achieve “buy-in,” Chiu said.

Oubre said she has not witnessed any information on biosimilars distributed by payers, and McBride said nonbranded biosimilar information would be useful.

One group that wants more information about biosimilars is employers, Oubre said. “Employers really want to know more. If something goes on formulary and a patient with breast cancer is switched and gets upset, an employer doesn’t want that.”

In a webinar this week, experts discussed the business dynamics that prevent providers from being able to choose the lowest-cost biosimilars.

Webinar: Choice Is Vital to Biosimilar Savings Picture

By 2023, as many as 20 biologic originator drugs could lose their patent protection, stimulating the development of more biosimilars. But many clinicians in the United States are still on the fence about incorporating biosimilars into their practice. A recent 

 discusses the emergence of biosimilars as a class of drugs from the viewpoints of clinicians on the front lines in oncology.

The medical science underlying biosimilars is solid, and it’s a matter of convincing physicians that these agents are as safe and effective as the reference products they’re based on, according to the article, which notes that large proportions of providers still have difficulty defining biosimilars successfully or understanding the differences between biosimilars and generics. Patients also may not know enough about biosimilars to accept them if recommended by providers.

The provider-patient hurdle is not the only one. Biosimilar developers must overcome patent obstructions that may delay the market entry of these drugs by many years. In the case of etanercept (Enbrel), an Amgen/Pfizer product, biosimilar developers have seen court defeats to their patent objections that may push back the first biosimilar arrival for this drug until 2029.

With the recent approval of an adalimumab (Hulio) biosimilar, a drug developed by Fujifilm Kyowa Kirin Biologics and commercialized in multiple countries by Mylan, there have been 2 biosimilars 

Currently, there are 28 US-approved biosimilars, 17 of which have been launched on this market.

A recent article lays out some of the hurdles the biosimilars industry faces, from the perspectives of oncology providers.
 