Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Many things may discourage patients and doctors from using biosimilars, but they don’t dissuade Gary Lyman, MD, MPH, senior lead for Health Care Quality and Policy at the Hutchinson Institute for Cancer Outcomes Research.

In an interview, Lyman talked about some of the most common concerns and why they don’t trouble him about using biosimilars in cancer care.

“Drift” is one of the biggies. It can happen in the manufacturing of batch after batch of a biologic drug—biosimilar or originator product. It’s a subtle change in the makeup of the drug that occurs because these drugs are made from living organisms and are impossible to replicate with exact precision. Even batches of originator drugs are slightly different from earlier batches.

But biologics can be kept within predefined margins of quality. “While careful monitoring of the multiple attributes considered critical to a biologic is necessary, I am perfectly comfortable with using biosimilars in cancer treatment,” he said.

However, significant drift leading to a potential change in safety or efficacy could happen as easily to an originator product as a biosimilar, and in fact, this was observed in a recent phase 3 study, Lyman said.

Investigators sought to assess the cardiac safety and efficacy of trastuzumab originator and biosimilar products in patients with HER2-positive early stage breast cancer. They observed what they called a downward drift in immune system activity, or antibody-dependent cell-mediated cytotoxicity, for the originator version of trastuzumab, which led to superior event-free survival in the biosimilar arm of the study.

For this reason, “continuous monitoring of manufacturing and pharmacologic vigilance after approval are essential for both biosimilars and the originators,” Lyman said.

When it comes to conducting the pharmacokinetic (PK) and pharmacodynamic (PD) assessments needed to verify that biosimilar candidate drugs are equivalent to biologic originators, technology today “is far superior to what was utilized a couple of decades ago,” Lyman said.

The quality of these assessments are why it’s possible to project from PK/PD studies that biosimilars are highly similar to originator drugs and that clinical trials will yield equivalent outcomes and therefore may not be necessary.

Still, clinicians have shown hesitancy to put biosimilars to the test. These agents have been accepted more widely for use as supportive care agents than oncology drugs, Lyman said.

“Clearly, clinicians are more anxious about cancer treatment biosimilars than supportive care agents due to the potential impact on cancer outcomes and survival. This is understandable,” he said.

There are other issues associated with the pace of uptake. Biologics are expensive, and biosimilars may not be offered at a very significant discount, Lyman said.

 that biosimilars would enter the market at discounts to originators of 30% to 40%, but such hefty initial discounts did not materialize. Actual discounts to originators were in the range of 10% to 20%.

The billions of dollars of predicted savings may be years away, but earnings reports for biosimilar companies do show steady improvement in market share for this class of agents. International (non—United States) 

 for Humira (adalimumab) were $863 million, down 19.9%, in the second quarter of this year, owing to biosimilar competition.

The danger is that having such limited competition in the biosimilar space may mean biosimilar manufacturers won’t be incentivized to offer deep discounts.

“In the United States, manufacturers of the initially marketed biosimilars may be more motivated to share in the very lucrative market of exorbitantly priced biologic therapies rather than compete directly by lowering prices significantly,” Lyman said.

“We do have some early evidence that the price associated with supportive care biosimilars has begun to decrease with multiple biosimilar competitors. Many of us hope that the prices of costly biologic agents for cancer treatment will also begin to decrease,” he added.

This may happen only slowly because of the way the US health care market is structured. “Lower prices are likely to improve access to these important agents and meaningfully reduce the financial burden or toxicity that patients with cancer experience on a daily basis.

“Although we remain hopeful that this will be the case, many believe that it will take more fundamental or structural change in health care financing in the United States for a real reduction in the enormous financial burden that patients with cancer and other serious illnesses face in the United States,” Lyman said.

noted that biosimilars are causing a decrease in health care costs for biologics around the world while arguing that structural changes are needed to help the process along.

Articles

Originator biologics should be monitored as closely as biosimilars, according to Gary Lyman, MD, MPH, of the Hutchinson Institute for Cancer Outcomes Research.

Lyman Reassures on Biosimilar Quality

Can you make a biosimilar package more appealing for a patient? What would you change? Those were the questions that designers at Samsung Bioepis pondered as they sought unifying design elements they could use across their drug portfolio while still enabling patients and doctors to distinguish one product from another.

They appear to have succeeded. The Incheon, Republic of Korea—based company won 2 prestigious 

 for its soft-yet-engaging product designs that feature basic shapes and soothing colors, such as a purple, fruit-like shape for its infliximab product (Renflexis, Flixabi, Remaloce) and a fusion of green or blue circular shapes for its etanercept biosimilar (Eticovo, Brenzys, Benepali, Etoloce).

Meanwhile, Samsung Bioepis’ trastuzumab contender (Ontruzant, Samfenet) was given a solid, salmon-colored tulip-like shape.

The company called the redesign “Passion for Health: Pure Joy in Life.” It draws from tranquil, organic forms to evoke mental and physical stability in patients who are struggling with their health conditions.

 “It was designed with a motive to bring out life and joy for patients with chronic illness,” Samsung Bioepis said. “The focus of the design was ‘process of healing’ by using soft graphics in order to move away from the conventional, rigid design of medicine packaging, which only serves to deliver safety information.”

Samsung Bioepis won the Brand Design & Identity and Packaging Design awards in this year’s Red Dot contest. The company has been part of a wave of biosimilar 

 powering up in Republic of Korea, which has enjoyed double-digit growth for the past 5 years.

In an award-winning attempt to get closer to patients, Samsung Bioepis has replaced harsh typography with white backgrounds and gentle shapes on its new biosimilar packaging.
 

Samsung Bioepis Appeals to Patients Through Package Design

Cadila Pharmaceuticals, of Ahmedabad, India, has launched a teriparatide biosimilar (NuPTH) indicated for osteoporosis and in patients with increased risk of fracture. The drug references Forteo, made by Lilly.

“India is the osteoporosis capital of the world,” Cadila said in a release indicating the company’s hopes pinned to this product and its potential. The company cited study data that estimated the population of individuals with osteoporosis in India measured 26 million. “It is estimated that by 2050, half of the world’s fractures will occur in Asia.”

The launch of NuPTH is the third biosimilar launched in as many weeks by Cadila, which in late July put 2 biosimilars on the 

: a rituximab (Ritucad) for the treatment of blood cancer and rheumatoid arthritis, and a bevacizumab (Bevaro) for the treatment of ovarian cancer, glioblastoma multiforme, colorectal cancer, breast cancer, lung cancer, cervical cancer, and kidney cancer.

Cadila said it will market teriparatide in a prefilled disposable pen, which is said would be both cost-effective and easy to use, thereby circumventing the tendency for patients to discontinue use if the delivery method is too complex. “The ease of use of delivery device is as important as development of new drugs,” according to Amit Ajmera, vice president of Cadila.

The company said the product strengthens its orthocare portfolio and helps to increase choice and access for patients with osteoporosis in India.

Teriparatide, a recombinant human parathyroid hormone, was the 

 osteoporosis treatment that stimulated the development of new bone similar to normal bone.

Osteoporosis occurs in postmenopausal women as a result of bone deterioration, or resorption, that is not accompanied by an equivalent level of new bone formation. Teriparatide has also been used for treatment of men with hypogonadal (excessive hormone production) or idiopathic (unknown causes) osteoporosis.

There has been some uncertainty about the length of time patients should be treated with teriparatide. A 2016 

 evaluated a 24-month course of the drug from the perspective of effects on bone tissue, bone replacement in resorption sites, and safety and fracture outcomes.

Investigators noted an improvement in outcomes for patients who took the full 24-month course and found that bone formation appeared to occur continuously during the entire period, “resulting in increases in bone mass, even in patients with low bone turnover induced by long-term previous anti-resorptive treatment.”

They concluded that, for patients on teriparatide, improvements in bone mass and strength and reduction in risk of fracture correspond to the length of treatment.

Cadila Pharmaceuticals charges ahead with yet another biosimilar launch in India, an osteoporosis agent referencing Eli Lilly's teriparatide drug Forteo.

Cadila Puts a Teriparatide Biosimilar on the Market

Biosimilar medicines made up the lion’s share of 2019 biopharmaceutical exports from the Republic of Korea, whose biopharmaceutical market is expanding rapidly.

The country exported $1.28 billion in biopharmaceuticals last year, 68.2%, or $874.5 million, of which were biosimilars, according to a report in the 

The Republic of Korea biopharmaceutical market also expanded to $2.17 billion in 2019, up 16.6% from the previous year, and the market has seen 10.2% annual growth over the past 5 years, the report said.

The United States imported $74.4 million in Republic of Korea biopharmaceuticals in 2019. Overall, Germany was the largest importer, at $264.7 million, followed by Hungary and Croatia, at $233.2 million and $119.5 million, respectively.

The United States also was the largest exporter of biopharmaceuticals to the Republic of Korea, at $382.5 million, followed by Switzerland, with $210.5 million, placing it firmly in second place, the report added.

Celltrion Healthcare’s infliximab (Remsima), rituximab (Truxima), and trastuzumab (Herzuma); LG Chem’s etanercept (Eucept); and Chong Kun Dang’s darbepoetin alfa (

), were among the Republic of Korea’s biosimilar exports in 2019, according to the report. 

For 2019, Celltrion was the largest biopharmaceutical products producer, followed by GC Pharma, LG Chem, Medytox, and SK Bioscience, the report said.

Biosimilar exports make up a hefty chunk of biologics and other drug exports from the Republic of Korea to the United States and Europe, according to a report.

Sizzling Growth for Republic of Korea Biopharmaceuticals Market 

Payers keep tight control of which biosimilars practices can use. Their contracts with vendors have a lot to do with what biosimilars get onto the preferred list. For providers, the freedom to choose among biosimilars of a drug type may be limited to just one biosimilar, or none at all.

Practices say they could be of better service to their patients and would find it easier to manage operations if they could do the biosimilar choosing.

Many audience questions asked during a recent MJH Life Sciences™ 

 about payer contracts had to do with the practice perspective on these issues. We asked panel participant Kathy Oubre, chief operations officer for the Pontchartrain Cancer Center in Louisiana, to assist, which she graciously did.

Below are her answers to questions on payer adherence, alternative contracting, cost preferences, and more. Oubre’s responses are infused with more than just her senior management experience—she is also president of the Louisiana Medical Group Management Association and a member of the board of directors for the Community Oncology Alliance.

Are you willing to quit a payer if they do not have all biosimilars in a class on their formulary?

Oubre: It would be unrealistic to quit a payer over biosimilar availability. In addition, patients on biosimilars account for a small portion of our overall patient mix; quitting a payer would result in forcing a much larger group of patients to seek oncology care elsewhere.

In your practice’s biosimilar strategy, do you consider partnering with biosimilar pharmaceutical companies that support an at-parity market approach?  

Oubre: Yes, we are more likely to work with a pharma partner who is interested in being a good community oncology partner and not enter into restrictive formulary deals with payers or distributors. Our organization is more likely to use the biosimilar of a company that promotes parity.

How often is a realistic frequency to do a benefits investigation on the next infusion? Before every infusion? For the next few months? For the year?

Oubre: Benefits investigations are done to determine whether the patient is covered for treatment. They are performed before the initiation of any new therapy and at the beginning of a plan year, when payers introduce plan changes and deductibles reset.

If a payer makes formulary changes on a quarterly basis, the formulary update is generally for new patients. Patients are generally not required to change if they are already receiving treatment. They would be “grandfathered” for their originally approved drug. Therefore, no interim benefits investigation would be necessary. 

Where is pegfilgrastim administered? In the doctor’s office or patient’s home? 

Oubre: It is administered in the doctor’s office.

Oubre: It is considered a medical benefit, not Part D.

Is there an incentive for the provider to administer pegfilgrastim in the office/hospital setting versus the patient self-administering at home? 

Oubre: There’s no incentive. There is a lot of discussion over treating patients at home because of the pandemic, but when they receive pegfilgrastim in the office it often results in better patient care. Having the patient return on Day 2 allows nurses to lay eyes on a patient and talk with them. Often, this brief encounter enables us to identify and treat nausea, dehydration, pain, etc, before the issue gets any bigger—which may require an emergency department visit or hospitalization.

In addition, most oncologists have policies against white and brown bagging (taking or receiving prescribed drugs outside the practice). Biosimilars are costly drugs and we cannot ensure proper storage and handling once the drug has left our facility or prior to, if it was brought in from a third-party supplier, such as a specialty pharmacy. We cannot prevent someone from leaving it in a hot (or extremely cold) car while running errands or delivering the drug to a patient’s front porch. There are many environmental factors, such as sunlight which may compromise the integrity of the drug.

Is there a higher co-pay for the patient if they self-administer at home?

What role do you see for biosimilars in value-based care (VBC) health care models? Are there any examples of VBC models with biosimilars?

Oubre: Biosimilars play a huge role in VBC models, since the primary goal of VBC is high quality/low cost. This is especially true for the Oncology Care Model. Pegfilgrastim biosimilars have enabled Pontchartrain Cancer Center to save money every time. There are some pilot programs coming out that will center on biosimilars, particularly in value-based care models. The Center for Medicare & Medicaid Innovation is talking about a pilot program specifically for biosimilars, as are several employer groups across the United States. 

Are you aware of any states that have taken steps from a policy perspective to decrease payer influence on formulary decision-making for biosimilars? 

Oubre: Several states are reversing their current policies and including biosimilars on their formulary after having allowed only originator products, based on rebates between pharma partners and state Medicaid programs. I do think there’s going to be more of that.

Many states, including Louisiana, are attempting to reform step-therapy policies that often require patients to fail first on the originator before being allowed to use the biosimilar. Under proposed legislation that has passed the Louisiana Senate, patients and physicians could appeal step therapy requirements that are not in the best interest of the patient based on medical necessity [

What biosimilar pricing discounts to brand do you need to switch?

Oubre: It’s not a simple question to answer. Practice formulary decisions are a marriage between a practice’s payer mix, drug contract structure, and pricing. I would say that at a minimum, a 10% discount is required. But it’s not as easy as flipping a switch. When you make these decisions at a practice level, it requires us to build the new drug into the treatment plans within the electronic medical record and contact the payer to obtain authorization for the new drug.  We do have to recover staff costs for those additional workflows.

What makes this process more complicated is that there are multiple biosimilars and practices may have several payers who all choose different products.  On a practice level, it’s important to consider the number of patients on a particular drug (I review my previous quarter or 2). Then I evaluate each drug based on practice usage, price differential, and contract metrics.  Every contract looks a little bit different. The biggest problem is multiple payers are picking different biosimilars, which makes it difficult for practices to perform well on many contracts.

For webinar questions and answers from the payer perspective, click 

An oncology practice administrator describes the careful calculus involved in balancing patient needs with the business side of biosimilars and cancer care.

Oubre: The Practice Perspective on Biosimilar Contracts

Herzuma, a biosimilar form of trastuzumab that was launched in the United States in March, has received World Health Organization (WHO) prequalification status, a Celltrion Healthcare spokesman confirmed.

Trastuzumab is used for the treatment of breast cancer, and the drug has been on WHO’s list of essential medicines since 2015. About 2.1 million women contracted breast cancer in 2018 and 630,000 died from the disease, often because of late diagnosis and poor access to affordable treatment, 

Trastuzumab is used in breast cancers that express 

, a gene that is associated with a faster rate of cancer growth and is present in 15% to 20% of breast cancers and in some gastric cancers.

WHO prequalification status is based on an assessment of the quality, safety, and efficacy of medicines and is intended to give providers the confidence to use medicines that are needed for high priority health concerns.

WHO has prequalified both the 150 mg and 420 mg versions of Herzuma. This is the second WHO prequalification for the Republic of Korea-based company. In May, Celltrion’s rituximab biosimilar (Truxima), used for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia, 

 WHO prequalification status, becoming the first rituximab product to gain that distinction.

Biosimilars offer a lower-cost alternative and are especially useful in lower income countries. The average global cost of trastuzumab from sources that provide the originator product, Herceptin, is $20,000, which “puts it out of reach for many women and health care systems in most countries,” WHO stated in December 2019.

This makes the second trastuzumab biosimilar to make WHO’s list of prequalified medicines. The first was a Samsung Bioepis medicine, 

, in December 2019, which WHO noted was 65% cheaper than the originator product. Ontruzant was launched in the United States in April 2020.

Herzuma was launched in the United States in March 2020 via Teva, a Celltrion partner. It received European Medicines Agency authorization in 2018.

According to a recent study, delays for treatment of breast cancer in sub-Saharan Africa (Uganda, Nigeria and Namibia) are often lengthy. Of 1325 women, cancer treatment was not initiated for at least a year for 17% of women and 14% of women with stage I-III disease. The untreated percentages were significantly higher in 2 regional Nigerian hospitals (38%).

World Health Organization (WHO) prequalification of Celltrion Healthcare’s trastuzumab opens the door for more affordable access to care for patients with breast and gastric cancers.
 

WHO Prequalifies Second Celltrion Healthcare Biosimilar

 a biosimilar rituximab (Ritucad) for the Indian market. The drug is used for the treatment of blood cancer and rheumatoid arthritis. Rituximab is used in the treatment of non-Hodgkin lymphoma. Each year there are more than 28,000 new cases of lymphoma in India, the company said.

This was the company’s second biosimilar launch announcement in a week. Cadila previously stated that the bevacizumab biosimilar Bevaro would be made 

 in India for the treatment of ovarian cancer, glioblastoma multiforme, colorectal cancer, breast cancer, lung cancer, cervical cancer, and kidney cancer.

Cadila is based in Ahmedabad, India. The company stated in the bevacizumab launch announcement that it intends to continue launching biosimilar products this year.

On the heels of its earlier announcement of a bevacizumab biosimilar launch, India-based Cadila Pharmaceuticals said it also has a rituximab biosimilar entering the marketplace.

Cadila Launches Second Biosimilar in a Week

The European Commission (EC) has approved the marketing of the trastuzumab biosimilar Zercepac, developed by Shanghai Henlius Biotech and set to be marketed by Accord Healthcare, according to 

 for the treatment of early breast cancer following surgery or chemotherapy and radiotherapy; metastatic breast cancer alone or in combination with other medicines, such as paclitaxel or docetaxel or aromatase inhibitors; and metastatic gastric cancer in combination with cisplatin and either capecitabine or fluorouracil.

The biosimilar trastuzumab is intended for use only in cancers that are 

-expressing, which is the case in about 25% of breast cancers and 20% of gastric cancers. The newly approved biosimilar references Herceptin.

Henlius is based in Shanghai, China, with research and development activities in California; and Accord is based in Ahmedabad, India, with a suburban office in North Harrow outside London, England.

Henlius has sought to develop international standing as a biosimilar company and in its statement today, officials said this approval demonstrates that the company is achieving that objective. “The approval of Zercepac in the EU is a significant milestone of our global strategy,” said Scott Liu, co-founder and CEO of Henlius. “This achievement announces that our capability in the development and manufacturing of biologics has reached international standards. In the future, Henlius will provide more high-quality biologics as new treatment options to benefit patients worldwide.” 

“Henlius strictly followed the [China National Medical Products Administration] and [European Medicines Agency] guidelines and has [done] multiple head-to-head comparisons between Zercepac…and the reference trastuzumab, including comparative quality studies, preclinical studies, a phase 1 clinical study and a global multi-center phase 3 clinical study. [The] manufacturing site of Zercepac and its quality management system have obtained EU [Good Manufacturing Practices] certificates,” the company said.

For Accord, the trastuzumab product marks the company’s first monoclonal antibody and therefore raises the company’s profile in the world of complex biologics, according to Paul Tredwell, vice president of Specialty Brands for Accord.

“Zercepac is an exciting new addition to our growing oncology portfolio, which now provides access to over 30 high-quality, cost-effective oncology treatments to patients across Europe,” he said.

Shanghai Henlius Biotech has been given the green light to market its trastuzumab biosimilar (Zercepac, HLX02) in the European Union. Accord Healthcare will handle the distribution.

Henlius Biotech Gets EC Marketing Approval for Zercepac

Amgen has a hand in both originator products and biosimilar products, so as biosimilars gained traction in the United States over the second quarter, Amgen saw an ebb and flow in its revenue picture.

 a 6% global increase in its product sales ($6.2 billion) compared with the second quarter of 2019, and its bevacizumab (Mvasi) and trastuzumab (Kanjinti) biosimilars played a notable role in that achievement; however, there was a chipping away that Amgen said could be attributed to the coronavirus disease 2019 (COVID-19) and biosimilar and generic competition.

COVID-19 was a major culprit working against the company’s struggles to boost revenues, Amgen said. Physicians have been unable to meet with patients, and as a result there have been delays in diagnosis and treatment. Inventory practices by companies looking to brace themselves against supply chain issues and demand fluctuations have also been a characteristic of the drug portfolio battering at Amgen and other companies.

“Sales of negatively affected products fell most early in the second quarter, with sales beginning to recover in the latter weeks of the quarter. As the quarter progressed, our teams increasingly responded to customer needs via remote interactions and also identified innovative solutions to support the delivery of patient care,” Amgen said.

Amgen’s etanercept blockbuster (Enbrel) clocked an important victory against biosimilars in the second quarter when the US Court of Appeals for the Federal Circuit 

 the validity of 2 Enbrel patents that had been challenged by Sandoz, which wants to bring a biosimilar etanercept (Erelzi) to market. Amgen is still duking it out with Samsung Bioepis, which is trying to get the Eticovo etanercept biosimilar into the marketplace. Assuming status quo, there may not be an etanercept biosimilar on the market until 2029.

Nevertheless, for Enbrel, which has the whole US etanercept market to itself, it was not a great quarter. Sales dipped 9% year-over-year owing to competition from other quarters, lower growth of the rheumatology treatment market because of COVID-19, and a decline in new patients. US sales of Enbrel were $1.21 billion in the quarter. Amgen reported total Enbrel sales of $1.25 billion for the second quarter and $1.36 billion for the comparable year-ago period.

Pfizer holds the rights to sales of Enbrel in Europe and other markets outside the United States, where biosimilars have had market access, and earlier this week Pfizer reported a 16% drop in core revenues for the product.

Mvasi and Kanjinti biosimilars were each launched in 2019 and their sales appeared to be on the upward trajectory, according to the Amgen report. Kanjinti brought in $101 million in US sales for the quarter just ended, or a total of $123 million, versus $30 million in the second quarter of last year. The biosimilar commands a 32% share of the US market for trastuzumab.

Amgen sounded a cautionary note with this information. “The trastuzumab market has become increasingly competitive,” it said, noting the launch of 4 biosimilars in the US market this year, 3 of which were trastuzumabs: Ontruzant (Samsung Bioepis), Herzuma (Celltrion/Teva), and Trazimera (Pfizer).

Mvasi registered $149 million in US revenues for the just ended quarter, $172 total, and nothing for the second quarter of 2019.  “Going forward, we expect increased competition in the United States, given the launch of a competing biosimilar earlier this year,” Amgen wrote. Mvasi ended the second quarter with a 39% share of the bevacizumab market in the United States.

The company also reported on the progress for 3 of its aging blockbuster originator products, each of now shares the market with biosimilars: Sales dropped 28% for Neulasta (pegfilgrastim), 35% for Neupogen (filgrastim), and 28% for Epogen (epoetin alfa). The respective dollar figures for total second-quarter sales were $520 million, $28 million, and $161 million.

Biosimilars were chiefly blamed for the decline in Neulasta sales, cutting into “net selling price and unit demand” although the company said National Comprehensive Cancer Network guideline revisions that recommended increase use of long-acting granulocyte colony-stimulating factors (G-CSF) helped to counter the decline in unit sales volume.

Further, the Neulasta Onpro wearable injector kit has demonstrated its value in the COVID-19 home-based care environment, Amgen said. “Within the long-acting G-CSF segment, Neulasta Onpro continues to be the preferred choice for physicians and patients, and [market] share increased to 58% this quarter. Onpro provides a unique value proposition during the pandemic as it allows patients to receive their G-CSF treatment without having to return to their doctor's office or other site of care for administration.”

The company said research and development expenses as a subset of operating expenses increased 3% in part because of higher investment in biosimilar development programs.

Big drivers in the revenue increase this quarter were apremilast (Otezla; $561 million), for psoriasis and psoriatic arthritis, and evolocumab (Repatha; $200 million), for hyperlipidemia, or high blood fat (lipids) control.

If you can’t beat biosimilars, join them, is the mantra; but at Amgen there’s still gold in originator products, according to its latest earnings report.

Amgen Reports Double-Edged Biosimilars Results

Kaiser Permanente has achieved very high biosimilar utilization, and a reason for this is that the payer is very largely a “closed system” with a large degree of control over decisions that are made on drug usage. Even so, there have been challenges to biosimilar uptake.

 included Timothy J. Chiu, PharmD, who serves as pharmacist evidence analyst and strategist for Hematology and Oncology at Kaiser Permanente. The panel of experts looked into how drug rebates are, in many cases, frustrating the ideals of biosimilar utilization, because they may disincentivize the use of the biosimilar that costs the patient the least. And when it comes to biologics, prices can be very high, and the use of lowest-cost biosimilars can be paramount.

Webinar audience members submitted questions for Chiu, which he graciously answered in this first of a series of articles on responses to these questions. Chiu discusses how Kaiser Permanente developed a system for addressing concerns about the risks of biosimilar switching, payer reluctance to push for biosimilar adoption, and various other key issues.

How concerned is Kaiser Permanente about differences in safety or efficacy when switching individual patients between biosimilars?

 Kaiser Permanente has taken a collaborative approach in potentially switching biosimilars, thus hopefully limiting any major concerns on switching. Initially the totality of evidence around a class of biosimilars is discussed with specialist leaders with the goal of addressing all questions and concerns about the potential switching regardless of treatment setting. This information is further relayed to discussions between frontline team members and patients as needed. The whole process allows for broad discussion and has led to a greater endorsement and comfort with biosimilars over time. Ultimately, most clinicians now are comfortable switching to biosimilars for their patients within the organization, which has translated to biosimilar use in a majority of patients in applicable arenas.

Has Kaiser Permanente’s closed system, which has a higher degree of formulary coordination and control across acute and ambulatory care, experienced the same challenges with biosimilars as the a-la-carte health care delivery model of preferred provider organizations and health maintenance organizations?

Although Kaiser Permanente has gained much biosimilar experience, even in preparation for the launch of Zarxio (filgrastim), there have been similar challenges to what has been reported by other models. For example, a lot of questions and concerns arose in the path leading up to eventual formulary and system decisions, including confusion about interchangeability status and meaning, how confident we should be in the available data and the use of extrapolation, or if there would be risks in switching in amid treatment or in the curative setting of oncology (or risk of flares for patients doing well on the reference product for inflammatory diseases). The learnings from all these conversations was that education and proactive engagement with clinicians and patients were essential to prepare for biosimilar strategies.

That said, Kaiser Permanente’s infrastructure may lead to some differences in implementation of the strategy once formed, including efficient communication channels, formulary decisions, and implementation, as well as information technology modifications to promote ease of transition to a biosimilar within one system.

Why do you think payers have hesitated to push for more adoption of biosimilars versus small molecule generics, which are always pushed?

There may be multiple important considerations for this topic, but some reasons could be financial incentives tied to biologics and how they are administered, not to mention their relatively more complex structure. A 2017 article in 

Biosimilars are relatively new and there may be initial hesitation by various parties before using these products. Small-molecule generics had a similar response when introduced but these days are widely embraced. A potential limited understanding about biosimilars may lead to concerns about differences in efficacy or a loss of stable maintenance of disease if products are switched, despite the totality of available evidence.

Biologic reference products may be associated with substantial rebates or agreements that may not incentivize a payer to change products.

Similarly, biologics are often administered in a clinic setting, thus reimbursement models may also affect decisions. This includes the potential for utilizing high-cost options if reimbursement is based on a percentage of the medication cost (where biosimilars are often substantially lower cost).

Payers contribute to barriers to biosimilar utilization, but can you dig into the financial incentives of "buy and bill" and how that influences the original treatment decision?

Financial incentives, including the buy-and-bill model, have been a barrier to biosimilar utilization—a higher-costing reference product with the 6% add-on payment would be favored over a biosimilar with a lower reimbursement, given its generally reduced cost. Thus, the relatively low uptake of biosimilars may be strongly influenced by models such as this. Perhaps Congress will pass legislation so that the payment for biosimilars is based on the average sale price of the reference product and the add-on payment is increased from 6% to 8%. Hopefully, these types of policy efforts will help change the dynamic and remove the incentives that may be stacked against biosimilars.

How do you see rebates affecting the future of biosimilars? Do you expect manufacturers to make rebates available to payers so that they will more likely include more biosimilars on formulary?

Rebates, or any financial incentive, can play a strong role in the future of biosimilars, where one of the primary objectives is to provide more and affordable options to the health care system. There have been plenty of discussions on how rebates may be used to as a disincentive for biosimilars (by financially favoring use of reference products; ie, “the rebate trap”). Along those lines, rebates may also be a method to help bring biosimilars into a favorable financial position when balancing all the incentives that payers and others consider. Ultimately, financial incentives, whether by contracts, rebates, or otherwise, that allow for a lower net cost to the health care system can assist in promoting biosimilars and affect decisions like formulary placement.

1. Hakim A, Ross JS. Obstacles to the adoption of biosimilars for chronic diseases. 

. 2017;317(21):2163-2164. doi:10.1001/jama.2017.5202

Biologics are not cheap, and if you can get biosimilars into the hands of patients, you’ve got something going. A strategist describes the step-by-step process that made this possible at Kaiser Permanente.