As the coronavirus disease 2019 (COVID-19) pandemic spreads, it will continue to affect the biopharmaceutical industry. Biosimilars are no exception, and the effect on their uptake and adoption will be multifaceted. Here are several ways that biosimilars are most likely to be influenced by COVID-19:

Inaccessibility of healthcare providers (HCPs) and other medical decision-makers:

 currently, COVID-19 is setting the priorities for most HCPs and hospital decision-makers: take care of affected patients, navigate the evolving COVID-19 coverage and payment landscape, and maintain an adequate supply of beds and personal protective equipment. During this time, institutions may lack the bandwidth to continue to evaluate complex biosimilar-related decisions and may stick to the status quo, the reference product, or the existing preferred biosimilar product until the dust settles. This will slow down biosimilar uptake across the board. As providers defer to their status quo therapy options to avoid unnecessary disruption, uptake of the 8 therapeutic oncology biosimilars 

 in the United States so far may be particularly hard hit.

Repurposed contracting and promotional activities: 

although many regular account manager activities have been disrupted by social distancing measures, contracting can be conducted effectively via digital media. This is especially true for biosimilar manufacturers with existing relationships or customers interested in immediate cost-saving opportunities who are not yet preoccupied with managing COVID-19. Many financial decision-makers (pharmacy directors, medical directors) are postponing contracting discussions. Account managers can now focus on bringing accounts on board for biosimilars and leave “pull-through” sales activity for later. Also, manufacturers that are preparing to launch biosimilars during this quarter or the next may decide to postpone marketing or do a soft launch, which would entail supplying product, leveraging digital or nonpersonal channels, and contracting via tele-detailing. This could affect biosimilars such as Merck's trastuzumab and bevacizumab biosimilars, Ontruzant and SB8, respectively, which are lined up for launch over the next 2 quarters.

COVID-19 is causing a dramatic mismatch of supply and demand that manufacturers are struggling to forecast. On the supply side, manufacturing and supply chain processes in hubs such as China, India, and the United States are being disrupted due to global lockdowns. On the demand side, conflated factors make demand difficult to predict. On one hand, patients delay seeking treatment, particularly for less convenient administration methods such as infusions, which can lead to lower patient volume and overall demand. On the other hand, stockpiling and demand for subcutaneous or oral formulations may cause a spike in demand for certain products despite decreasing patient volume. In February 2020, the FDA 

 the first case of a shortage of a drug due to coronavirus. Although all manufacturers are working to mitigate the risk of supply shortages, biosimilar manufacturers that rely on facilities in Europe and Asia may be particularly at risk on the supply side (

Delays in biosimilar approvals and clinical trials: 

most clinical trials are likely to be delayed due to challenges managing protocols, deprioritization in favor of more immediate acute care needs, and patients’ inability to travel to appointments. Beyond the logistics and prioritization challenges, manufacturers run the risk of trial participants contracting the disease, which leads to 

 on how to manage clinical trials during the pandemic. All of the above-mentioned complicating factors are likely to undermine Prescription Drug User Fee Act/Biosimilar User Fee Amendments dates for biosimilars with approval decisions scheduled by the end of 2020 (

Increased budget pressure can accelerate postcrisis biosimilar usage: 

Without a doubt, the current situation is putting significant budget pressure on the health system, with many providers 

 copays, coinsurances, and out-of-pocket costs due to COVID-19. Although the broader impact on the economy and health system is still unclear, what is certain is that after the crisis, providers will actively look for ways to compensate for the extra expense they are incurring now, and it will be more important than ever for biosimilars to deliver on their promise to bring savings to the healthcare system. In the meantime, it will be important to monitor what manufacturers of reference products and biosimilars do to help support providers as this situation evolves.

There are additional aspects of the pandemic that will affect both biosimilars and reference products alike, such as ensuring safe supplies of medicine in patients’ homes as we all observe social distancing. Patients, either on their own or in consultation with their HCPs, may start to make adjustments to treatment regimens to allow for less time in the hospital or the clinic, especially when it comes to biologics that suppress their immunity, as also recommended by 

Such recommendations, along with the already limited infrastructure, overburdened healthcare system, and social distancing policies will create a very difficult environment for biologics and biosimilars businesses in the short and medium term. However, companies can think strategically about how to create opportunities from these difficult circumstances, such as leveraging virtual technology for contracting discussions, stressing cost savings with cash-strapped customers, and improving patient-support wraparound services. These will help them set the stage for success in a post—COVID-19 world.

At the end of the day, the priority for everyone right now is protecting health and safety. Although biosimilar adoption and evolution to new treatment paradigms may stall, we firmly believe that health and safety are foremost in mind for providers everywhere.

Christina Corridon, MPH, MBA, is a principal in ZS’s Boston office and leads the firm’s biosimilar vertical. Scott Kniaz, MBA, is a strategy insights and planning manager in ZS’s Washington, DC, office. Will Gatziolis, MBA, is an associate principal in ZS’s New York office. Ross Shahinian is a strategy insights and planning manager in ZS’s New York office. Sandeep Sangwan, MPharm, is a knowledge management consultant in ZS’s New Delhi office.  All are key leaders in the ZS biosimilar vertical.

The coronavirus disease 2019 (COVID-19) effect on the biosimilar industry will be deep and lasting, causing not just approval and launch delays but profound structural changes in how business is done.
 

COVID-19's Multifaceted Effect on Biosimilars

Scott Kniaz, MBA

Another study from Europe found that biosimilar etanercept was effective and well-tolerated in the majority of patients who switched from originator etanercept.

The study looked at Samsung Bioepis’ biosimilar, SB4, which is sold as Benepali in European countries. 

 have also found SB4 to work well for the majority of patients who switched from the originator etanercept, Enbrel. The anti-tumor necrosis factor (anti-TNF) inhibitor, is currently prescribed in the United States for rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis (PsA), ankylosing spondylitis, and plaque psoriasis.

An observational study conducted in Poland looked at patients being treated for RA, juvenile idiopathic arthritis, PsA, or ankylosing spondylitis, in which the originator etanercept replaced SB4.  

Etanercept was replaced with SB4 in 162 patients (Group 1), and in another 6 patients SB4 was the initial biologic used (Group 2). Efficacy and safety were assessed over a 6-month period.

The biosimilar was effective and well-tolerated in the majority of patients, however, for 24 patients in Group 1 (14.8%), returning to the originator was necessary due to loss of efficacy or adverse events.

Previous observational studies have found rates of discontinuing the biosimilar ranging from 2-14%. Specifically in this study:

9 patients experienced clinically confirmed loss of efficacy

9 patients reported subjective loss of efficacy

13 patients reported adverse events, the most common of which were headache and skin lesions.

Of the 24, returning to the originator reversed the loss of efficacy or resolved the adverse event. No adverse events were reported in the 6 patients for whom the biosimilar was the initial therapy (Group 2), and the biosimilar was effective in these patients.

The authors conclude that SB4 was effective and well-tolerated in most patients, but that further research is required to investigate the effects of switching patients between originators and biosimilars.

Felis-Giemza A, Chmurzy&#324;ska K, Na&#322;&#281;cz-Janik J, et al. Observational study of inflammatory arthritis treatment by etanercept originator switched to an etanercept biosimilar.

2019;57(5):257—263. doi:10.5114/reum.2019.89516.

The study follows others that have found that SB4 works well for the majority of patients who switched from the originator etanercept, Enbrel.

Another European Study Finds SB4 Tolerated by Most Patients

Peter Page

 that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar. The agreement authorizes Mylan to market the potential biosimilar in Europe, Australia, New Zealand, Latin America, Africa, and Asia.  

Etanercept is an anti—tumor necrosis factor (TNF) inhibitor indicated to treat rheumatoid arthritis (RA), plaque psoriasis, ankylosing spondylitis, and other autoimmune diseases. Enbrel generated $5.2 million in 

Vinita Gupta, CEO of Lupin commented on the collaboration, 

, “We are extremely pleased to announce this partnership as both Lupin and Mylan share a commitment to bring affordable and high-quality medicines to market, especially in areas of unmet need.” 

 that Mylan has developed with a pharmaceutical company to accelerate a biosimilar commercialization. In April 2018, Mylan entered a partnership with Fijifilm Kyowa Kirin Biologics to launch its adalimumab biosimilar, referencing Humira, in Europe. 

“The introduction of biosimilars is an important mechanism to help increase access to more affordable biologics treatments, and our industry-leading portfolio of 20 biosimilar products positions Mylan to be at the forefront of delivering those sales,” said Rajiv Malik, president of Mylan of the collaboration. 

The proposed etanercept biosimilar completed a phase 3 clinical trial in February 2018 with a successful outcome. The 52-week trial, which included more than 500 patients with RA in 11 countries, compared the efficacy and safety of the proposed biosimilar directly with the reference product. 

Under the terms of the agreement, Lupin will receive an upfront payment of $15 million as well as an equal share in net profits of the product. The potential biosimilar has been filed with the European Medicines Agency and Japanese regulatory 

, and is planned to be filed in other domains.  

Lupin recently announced that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar.

Lupin Partners With Mylan on Etanercept Biosimilar

Christine Potkul

Will Gatziolis, MBA

Andre Harvin, PharmD, executive director of pharmacy and oncology services at Cone Health, explains how oncologists can work with other stakeholders to expand access to biosimilars and how patients can work with providers and biosimilar manufacturers to address financial challenges.

What more needs to be done to ensure that oncology and supportive care biosimilars are affordable and accessible for patients with cancer?

The affordability and accessibility that biosimilars bring to us is something that cannot be understated. I think one of the challenges sometimes is how it relates to the finances of your overall cancer center. Sometimes there's a lot of misinformation out there. Sometimes it's disinformation as well. We have to understand what the finances are around how expensive medications are, what we charge—whether it be the insurance company or Medicare and Medicaid—and then actually understanding how we're reimbursed. What I've been surprised by in my career is that how few people, sometimes in decision making roles, within oncology don't really have a full grasp of how they're actually reimbursed for medications.

I encourage everyone that's out there listening to actually sit down and ask those questions. You know, bring in your revenue cycle management team, bring in your managed care team. Obviously, bring in your pharmacy team, because there's a lot of things at play here. First, you have to understand how much you're paying for the drug and if there are any rebates or any contractual arrangements that are important. Next is how much you're charging for it. But most importantly, it's how much money is actually coming back in.

When you actually sit down and do that analysis, I think most people will find that biosimilars really affords them a much better financial picture than some of the reference products and that's why it's so critical to really understand the financial implications of biosimilars rather than getting caught up in the previous dogma of more expensive drugs means higher margin. That's not always the truth. And biosimilars has really changed the way we have to approach the finances of health care.

But once we do that, then we also have to think about the accessibility aspect. So, depending on patients insurance, a more expensive drugs may, obviously, decrease their ability to have access to that medication. If they have excessive out-of-pocket [costs], where they have to be charged a percentage of the total charges out-of-pocket, some patients start making decisions based on the cost of their therapy, and that's exactly what we don't want to occur.

So, the other aspect that's really great about having biosimilars and having a number of them out in the market is that every single one of them has their own patient assistance program. And so, if there is that question of the affordability or the accessibility of care, the great thing is you can engage those manufacturers, you can understand what their patient assistance programs are, and you can find ways to work with them to ensure patients have access to those critical medications.

Dr Andre Harvin Answers How Oncologists Can Work to Expand Access to Biosimilars

Maggie L. Shaw

In autologous stem cell transplantation, 

 of peripheral blood stem cells (PBSCs) is crucial, and the use of granulocyte colony-stimulating factor (G-CSF) therapies plays a key role in ensuring success. Lower-cost biosimilar G-CSF agents may be a way to reduce the overall cost of treatment, and in a recent study in a single center in Singapore, researchers found that a biosimilar filgrastim, Pfizer’s Nivestim (sold in the US market as 

), was safe and noninferior to its reference, Neupogen, in mobilizing stem cells for autologous stem cell transplantation.

, all patients who underwent autologous stem cell transplantation between 2011 and 2016 were included in the retrospective cohort. Those treated up to March 2014 (n = 66) had received the reference filgrastim, while those treated afterward received the biosimilar (n = 65). Patient characteristics were similar with the exception of chemo-mobilization regimen.

The primary outcome of the study was the proportion of patients who had successful mobilization, which was defined as a harvest of at least 2&thinsp;×&thinsp;10

In the biosimilar group and the reference group, mobilization was successful in 96.9% and 97% of patients, respectively (

= .988). The authors noted that the number of CD34+ cells mobilized was higher in the biosimilar group, although the difference did not achieve statistical significance. Safety was also similar; the incidence and severity of adverse events were comparable between the groups, with headache, back pain, and bone pain being the most commonly reported.

Notably, the median length of hospital stay required for mobilization was significantly shorter in the biosimilar group (15 days) than in the reference group (17 days), and the duration of G-CSF use per mobilization was lower in the biosimilar group (9 days) than in the reference group (10 days).

Using the biosimilar also resulted in a significantly lower drug acquisition cost, at $533.40 in the biosimilar group versus $1261.90 in the reference group (

According to the authors, using the biosimilar to mobilize stem cells was both safe and noninferior to using the reference filgrastim, and results in a lower drug cost and a potentially shorter length of hospitalization.

Chew C, Ng HY. Efficacy and safety of Nivestim versus Neupogen for mobilization of peripheral blood stem cells for autologous stem cell transplantation [published online December 27, 2019]. 

Using the biosimilar resulted in a significantly lower drug acquisition cost, at $533.40 in the biosimilar group versus $1261.90 in the reference group.

Using Biosimilar Filgrastim May Lead to Shorter Hospitalization, Lower Cost in PBSC Mobilization

Kelly Davio

Brian Lehman, MBA, MHA, RPh

A much-awaited talk at the 2017 AAM Biosimilars Council Conference, held in Washington DC, was by Andrew Slavitt, senior advisor, Bipartisan Policy Center and former acting administrator, CMS. Providing an overview on where the healthcare reform debate is headed, Slavitt refined the discussion to focus on drug cost and indicated the potential for biosimilars to influence the rising costs of drug products.

 that were being held by senators on the same day, where the lawmakers were to unveil new healthcare reform proposals, Slavitt predicted, “To my mind, every 10 years or so, we are due for another healthcare debate in this country. If you go back as far as Medicare and Medicaid, Medicare Advantage, Medicare Part D, Obamacare, and then of course the current battle…this could be another battle of sorts in 10 years.”

Slavitt went on to take stock of what the Affordable Care Act (ACA) accomplished, including reducing the uninsured rate, investing in healthcare cost and quality of care, and ensuring healthcare insurance for all American citizens, independent of their health or financial status. He acknowledged that the ACA did not get it all right in terms of fixing problems, including affordability of healthcare, which encompasses the absence of competition in the insurance marketplace in several states.

Slavitt said that every American should have access to affordable care, preventing healthcare-associated bankruptcy. Ensuring this can be sustained and achieved by 2020, the current focus should be:

Bipartisan legislation with complete support from 60-70% of the American public. This requires a discussion of the kitchen-table issues, he said, and an understanding of the tradeoffs faced by American families.

Implementing some of these ideas in the states over the next few years

Addressing cost and affordability of healthcare

Unlocking the innovation potential in the country in the right way

The healthcare challenge in our country, Slavitt explained, “is not the 50-year old jogger with mobile monitoring devices. The challenge is the woman who lives 2 bus stops away from a dialysis center and who may be in renal failure if she misses one of the connections.” Social determinants of health, which are outside of healthcare control, need to be addressed, he said, adding that we need to move innovation away from gadgets like Fitbit and refocus on some of these social issues.

Moving the discussion toward drug costs, he said that this problem is not forthcoming; it’s a problem we face today. “We cannot talk about affordability of healthcare in exchanges without getting into the underlying root cause.” Narrating his experiences of heading CMS, he said that, when he would talk to heads of healthcare systems or the pharmaceutical industry about keeping down or regulating the cost of care, the feedback would be:

Don’t look at me, look at them (plans, pharmacy benefit managers)

Don’t worry about the price, nobody pays it all anyway: lack of transparency is a problem

You have to spend money to make money: but this can be balanced off with real-world evidence and assigning “value” to the outcome with a specific treatment

Innovation costs money, but is price the tradeoff to make when choosing between innovation and improvements? If other industries continue to provide innovation at lower costs, why not healthcare?

“This is where biosimilars come in,” Slavitt said. He made note of changes being made by FDA Commissioner Scott Gottlieb, MD, to 

He reiterated his faith in competition, innovation, value-based ideas, and the ability for CMS to negotiate drug prices. Going back to the 

, which is being presented by Senator Bernie Sanders (I-Vermont), he said there are provisions in his bill and opportunities that are relative to generic drugs and biosimilars.

He closed by saying that the affordability questions will be ever-present, and that biosimilars and generic drugs may have a significant role to play in being part of the solution. “Being there and part of the solution while key legislations are being drafted or as people are focused on policy issues is a great place to be.”

Providing an overview on where the healthcare reform debate is headed, Andrew Slavitt, former head of CMS, refined the discussion to highlight the potential for biosimilars to influence the rising costs of drug products.

Federal Perspective on the Biosimilar Influence on Drug Costs

Surabhi Dangi-Garimella, PhD

test contributor 2

Ed Schoonveld is a managing principal at ZS Associates and is the leader of the firm’s value and access practice. In this role, he provides strategic consulting and research solutions to healthcare industry clients. He is considered one of the world’s leading experts on global pharmaceutical pricing and market access, and has unparalleled experience as head of global market access and pricing functions. He is the author of the book 

Authors