Tony Hagen is senior managing editor for The Center for Biosimilars

It is tough enough to get manufacturers to take the plunge and develop biosimilars for even-lucrative drugs that address major diseases, so what are the chances of seeing biosimilars developed for orphan drugs? Very slim, said a panel of experts who spoke at the Festival of Biologics USA conference.

Orphan drugs address conditions that affect relatively small patient populations, and it is difficult to recruit patient populations large enough for clinical trials needed to prove that experimental drugs are going to be efficacious. The expense of development and the small patient base for these agents translate into very high prices, which it is why it is desirable to have lower-cost biosimilar versions.

But with orphan drugs, biosimilar developers face almost the same set of difficulties that originators do. “When you’re talking about biosimilars, this can be considered even more challenging,” said 

 executive director of Global Biosimilars Regulatory Affairs and Regulatory and Research and Development Policy at Amgen.

Biosimilar companies need samples of originator drugs so they can develop their own versions of these agents, but with orphan drugs, access to drug samples is heavily controlled, she said. After that come the clinical trials, and, again, recruiting patients is difficult and time consuming. Patients may not want to participate in clinical trials with a biosimilar candidate if they know that their rare condition is already in stable condition on the originator drug, which further narrows the already small pool of available trial candidates, Christl said.

It may therefore be helpful if regulators are flexible in their demands for evidence used to support orphan drug development and willing to consider alternative means of demonstrating bioequivalence between biosimilar candidates and reference products. “But where should you look for flexibilities from the regulatory and scientific side?” Christl asked. “Can you conduct studies, maybe, in healthy individuals?”

Regulatory approvals that are more reliant on molecular characterization than clinical trials might also be possible, she said. Along the way, it’s important to ensure that patients and providers are confident in the process used to establish biosimilarity. “We need to find ways that are right, from a scientific perspective, to answer the question, to maintain the confidence in those regulatory pathways and what regulators are doing when they’re approving a biosimilar,” she said.

Whatever happens, standards for approving biosimilars cannot be lowered for the sake of making it easier to have affordable medicines, said panelist 

 who served 8 years with the FDA, most recently as acting deputy director of Therapeutic Biologics and Biosimilars. “The FDA has an approval standard, and any product it approves has met that standard. There may be different pathways to that same end point. It may be that one product is approved based on more analytical data—tighter analytical data—and a different pharmacodynamic end point.”

The desire for less costly versions of originator drugs for orphan diseases is just as strong in Europe, said 

director of Biosimilar Policy and Science for Medicines for Europe, an industry group for generics and biosimilars producers. “The price tags are really high, so it’s a problem for patients and for health care systems if there is no prospect of competition ever.”

“In the orphan space in Europe, we are up for a very big overhaul of the regulation and legislation around this. I’m expecting that there will be quite a substantial amount of discussion, not only scientific, but bringing the science and the regulatory processes to serve that purpose and meet those objectives,” she said.

In Europe there have been incentives and other support granted to encourage the development of even originator drugs for orphan diseases, and the question is whether biosimilars will emerge for orphan drugs without the same incentives that were offered to originator companies, Maréchal-Jamil said. “Less than 11% of those orphan biologics have biosimilar candidates in development at the moment, so that gives a little bit of a perspective on the difficulty for biosimilar developers to overcome the risks that are set in front of us at the moment.”

For coverage on the regulatory environment for biosimilars from Festival of Biologics USA, click 

Articles

Festival of Biologics

Potential developers of orphan drug biosimilars face daunting challenges to get these drugs approved and onto market, said a panel of experts. 

Are Orphan Drug Biosimilars Too Costly and Difficult to Produce?

In the court of expert opinion, clinical efficacy studies for evaluating biosimilar equivalence to reference products increasingly stand in a gray area. Many experts agree they are not sensitive enough in comparison with other tests to provide convincing evidence of biosimilarity, but regulators in the United States and Europe still hold onto their right to require these tests for biosimilar approval. The United Kingdom’s recent decision not to require these tests, therefore, is “revolutionary,” said 

 who leads Regulatory Affairs Policy at Sandoz and spoke at the Festival of Biologics USA conference.

“This is the way the future will look, so we will see more complex biologicals, which can be developed as biosimilars, without the need for these very large efficacy studies, and the evidence to ensure the safety and effectiveness of biosimilars will be collected by other means,” such as pharmacokinetic studies, Schiestl said.

Such regulatory changes can significantly improve the landscape for biosimilar development and acceptance, panelists at the conference agreed, but too much divergence between national policies can be a hindrance, as it adds complexity, said 

Biosimilar Policy and Science for Medicines for Europe, an industry group for generics and biosimilars producers. “Complexity is never really linked to access or availability in the end. That is just an additional hurdle.”

But it’s important to note that biosimilar approvals are based on the “totality of evidence,” and although the data that regulators will require may be voluminous and diverse, it is certainly not “one size fits all,” panelists said. In other words, US and European regulators are willing to be flexible in their requirements for individual biosimilar applications.

“I think we’re going to see the FDA and the European Medicines Agency be more open, and hopefully that will influence other regulators about what types of data and studies are really necessary to demonstrate biosimilarity," said 

Christl previously headed up the therapeutic biologics division at the FDA, and drawing on that experience, she said the FDA has tended not to provide micro-level, rigid guidance about biosimilar approval requirements simply because it makes sense to stay flexible so that it’s possible to adapt to changing needs and situations.

“You can target the data you need to look at—are there clinically meaningful differences between the products?—and look across the spectrum of different scientific studies, whether they are in the analytical space, looking at functional data or pharmacodynamic end points, vs those traditional clinical end points. I expect that the FDA is going to keep moving forward with that same type of approach,” she said.

Perceptions about what data are essential for biosimilar characterization may change, but ultimately one of the hurdles that must be crossed is the acceptance factor among providers and patients. They’re the ones who need to be convinced, ultimately, that biosimilars are safe and efficacious, so the requirements for regulatory review have to be tailored, somewhat, in that regard, said 

 who served 8 years with the FDA, most recently as acting deputy director of Therapeutic Biologics and Biosimilars. 

“There’s a real push-and-pull that regulators are grappling with around these issues," she said. "On the one hand, there’s a desire, and I think appropriately, to have efficiencies wherever we can and to really harness the flexibility that’s built into the 351(k) biosimilars approval pathway, and to exercise that flexibility appropriately. On the other side of that coin is that we also have patients and health care providers who need to be driving uptake and utilization of these products for that piece of this puzzle to be successful.” Temkin is now in private practice with King & Spalding in Washington, DC.

Insulin products, which are now approved under the Biologics Price Competition and Innovation Act, could help open the door for simplification of regulatory requirements, such that gaining FDA approval for substituting these biosimilars with established brands will be put on an easier gradient, said 

 of Axinn, Veltrop & Harkrider. “I’m sincerely hoping that because insulin is so well understood and such a simple protein, the FDA will be able to work with those who are seeking an interchangeable designation so that the immunogenicity clinical trials, which seem to drive up the cost of development for follow-on biologics, will not be required.”

That, in fact, is the direction the FDA wants to go, Temkin said. “My understanding is that the elimination of that requirement will save many, many months and potentially millions and millions of dollars from the development of biosimilar and interchangeable insulins, which can hopefully catalyze some additional development of those products.”

Regulators want built-in flexibility, and that benefits biosimilar developers, but there can be a price for this amount of latitude, panelists said.

Biosimilar Experts Debate Divergence in Regulatory Standards

Early adoption of the trastuzumab biosimilar Kanjinti was high among patients with breast cancer whether or not they had prior use of the originator (Herceptin), investigators said in a poster presentation at the National Comprehensive Cancer Network (NCCN) Virtual Annual Conference 2021.

Investigators set out to measure how quickly patients with a breast cancer diagnosis were started on the biosimilar during the agent’s first year of availability. Kanjinti, an Amgen product, was launched in July 2019. They used Flatiron Health retrospective data to develop 2 patient cohorts: those with early breast cancer (eBC, n = 2149) and those with metastatic breast cancer (mBC, n = 799). Those cohorts were further subdivided into patients with prior reference product (RP) exposure and no RP exposure.

Investigators said that among trastuzumab-naïve patients, the median time from diagnosis of eBC to initiation of biosimilar trastuzumab was 34 days; the respective time for those with a diagnosis of mBC was 30 days.

Among patients with prior RP exposure, 81% of patients with eBC transitioned and 75% with mBC transitioned to the biosimilar within 28 days of the final administration of RP. “Use of [Kanjinti] was observed in both RP-naïve and prior RP-treated patients, with evidence showing comparable patient characteristics between the 2 groups,” investigators wrote (

The investigators found that the first providers began to employ the trastuzumab biosimilar soon after it was launched—within 4 and 12 days of market entry. In the United States, Kanjinti was the first trastuzumab biosimilar to be launched, although it was not the first trastuzumab biosimilar to be approved by the FDA. 

The study did not evaluate for reasons why patients previously treated with RP were transitioned to the biosimilar, owing to a lack of appropriate data, investigators said.

Jin R, Accortt NA, Sandschafer D, Lawrence T, Mahtani RL. Characteristics of breast cancer patients treated with trastuzumab-anns, a trastuzumab biosimilar, in a real-world setting. Poster presented at: NCCN Virtual Annual Conference 2021; March 18-22, 2021. Accessed March 18, 2021. https://www.nccn.org/professionals/meetings/annual_conference_2021.aspx

NCCN  Virtual Annual Conference

Investigators observed early adoption of the trastuzumab biosimilar Kanjinti in patients with early breast cancer and metastatic breast cancer. 

Study: Rapid Adoption Noted for Kanjinti During First Year of Availability

Oncology providers are, in general, highly sensitive to costs of biologics, so expanding payer coverage of these agents to include lower-cost options is likely to drive adoption of biosimilars in oncology, said Sonia T. Oskouei, PharmD, BCMAS, DPLA, vice president of Biosimilars at Cardinal Health.

“From our surveys we know that the top 2 reasons oncologists are likely to prescribe a biosimilar are if it provides costs savings to the patient or practice or if the insurance company mandates a switch,” Oskouei said at this year's Association of Community Cancer Centers (ACCC) 47th Annual Meeting & Cancer Center Business Summit. Her presentation covered motives and biases that influence the prescribing behavior of oncologists.

A 2017 Cardinal Health survey identified fear of monetary loss as the chief bias influencing physician decision making in oncology, with 23.9% of respondents in agreement. These same physicians identified a strong bias toward following established guidelines from such nationally recognized entities as the National Comprehensive Cancer Network and the American Society of Clinical Oncology (22.0%). Lack of clinical response and the predictability of outcomes were 2 other factors that oncologists identified (16.5%) as influencing their likelihood to prescribe biosimilars.

“The responses really haven’t changed that much since 2017. This is a consistent theme when it comes to biosimilar utilization—the correlation to cost savings,” Oskouei said.

Whereas physicians may gravitate toward biosimilar use to save money, value-based care programs, such as alternative payment models (Oncology Care Model, Oncology Care First, Merit-based Incentive Payment System) are accelerating that trend, she said. “Biosimilars are really valuable tools for providers practicing in the value-based care initiative. These are ways to allow cost savings and efficiencies in delivering high-value cancer care and expanding the use of biologic treatment.”

In fact, loss aversion is a very powerful motivator in the oncology sector. Asked in 2017 how often fear of not being reimbursed influences their prescribing habits, 37.1% of oncologists answered “very often," and 25.8%, “moderately often.”

“The fear of monetary loss has double the impact of any potential equivalent gains, studies have shown, so it makes sense that this would be a primary driver of potential bias,” Oskouei said.

Familiarity with biosimilars plays a large role in acceptance and use, she said. Oncologists were first introduced to biosimilars via supportive care products, which as indirect treatments for cancer present a lower-stakes risk for oncologists. Their positive experience with these products may have contributed to their acceptance of therapeutic oncology biosimilars, she said.

However, familiarity also may mean a dependence on peer experience with and willingness to adopt biosimilars. For example, in a 2017 survey, 64% of oncologists agreed that they expected to be early adopters of biosimilars, but 33% said they would wait for other academic and community leaders to adopt biosimilars before prescribing them themselves, and the remaining 4% said they would not use biosimilars unless mandated to do so by payers.

“They’re trying to develop that familiarity and see peers utilize biosimilars and build more confidence in the outcomes before adopting,” Oskouei said.

Oncologists’ confidence in biosimilars may be biased by the statements about them written by the FDA and other authorities, she added. For example, the statement “Biosimilars are not inferior to reference products in terms of safety and efficacy” is less convincing than “Biosimilars are as safe and effective as the reference products."

Indeed, the FDA has considered rephrasing biosimilar language to get around the bias that such cautious language induces.

Differences in the language used to present biosimilar is known as “framing,” and these differences have the potential to influence decisions about the use of these agents, Oskouei said. 

“A lot of educational efforts and programs have helped address the potential framing bias with biosimilars,” which has turned up in literature from not only the FDA but also health care industry sources, she said.

When it comes to biosimilar uptake, a lot depends on physician education, but other agents and drug developments also play a role. Originator manufacturers are continuously innovating, developing new formulations of existing treatments, new methods of delivery, and also new medicinal products entirely, Oskouei said.

“We can’t just look at the originator biologic and the biosimilars in silo when making treatment decisions, because there are continued advancements and novel dosage forms that can compete with biosimilar utilization. Conversely, there’s also the discussion around obsolescence when it comes to biosimilars and their originator biologics,” she said. “The key message is that it’s really going to continue to be a very dynamic market.”

Oskouei ST. Biosimilar adoption in oncology: how attitudes have changed and what’s ahead? Presented at: ACCC 47th Annual Meeting & Cancer Center Business Summit; March 1-5, 2021. Accessed March 5, 2021. https://www.accc-cancer.org/home/attend/accc-47th-annual-meeting-cancer-center-business-summit/agenda#undefined5

ACCC Annual Conference

Sonia T. Oskouei, PharmD, BCMAS, DPLA, vice president of Biosimilars at Cardinal Health, discusses motivating factors that affect use of biosimilars in oncology.

Oncologists' Cost Sensitivity May Drive Biosimilar Uptake

Biosimilars have become largely integrated within oncology therapeutic and supportive regimens, and surveys of oncologists indicate these professionals are increasingly comfortable with not only using these agents but substituting them for originator biologics, according to Sonia T. Oskouei, PharmD, BCMAS, DPLA, vice president of Biosimilars at Cardinal Health.

Biologics spending predominates over small-molecule drugs in oncology, antidiabetics, and immunology, so there is an outsized potential for biosimilar growth in those classes of drugs, Oskouei said at the Association of Community Cancer Centers (ACCC) 47th Annual Meeting & Cancer Center Business Summit, March 1-5, 2021.

Filgrastim biosimilars were introduced to the US market in September 2015 and have achieved a 90% share of the market for this agent, which is used to boost white blood cell count following chemotherapy, Oskouei said. Bevacizumab biosimilars entered the market in July 2019 and now command a 59% share of their respective market. Bevacizumab is used for treatment of ovarian, cervical, renal, non–small cell lung, and colorectal cancers, among others.

Trastuzumab, for breast, stomach, and esophageal cancers, entered the market in biosimilar form in July 2019; these biosimilars now have a 43% share of their respective market. The comparable date and market share for rituximab, for autoimmune diseases and cancer, are November 2019 and 48%, respectively, according to Oskouei.

“The vast majority of biosimilar experience in the United States is in the oncology space currently. Just in December we had a fourth pegfilgrastim biosimilar become available and in January 2021 we had a third rituximab bisosimilar” enter market, Oskouei said.

Pegfilgrastim biosimilars, with 31% market share in the United States, have achieved the lowest share among biosimilars in oncology, although this is partly attributable to the Neulasta Onpro, a reference manufacturer product that offers the convenience of home-based injections.

Surveys conducted by Cardinal Health have yielded insight into oncologists’ improving disposition toward and knowledge of biosimilars. Whereas just 30% of those surveyed in 2017 (n = 61) stated they were very familiar with biosimilars, 53% said they were very familiar with biosimilars in 2020 (n = 195).

The survey findings also suggest that providers are increasingly likely to prescribe biosimilars for their patients. Asked whether they would prescribe biosimilars for new patients, 53% answered yes in 2017 (n = 93) vs 67% in 2020 (n = 195). The same study suggested that those willing to prescribe biosimilars for patients who were successfully treated with reference biologics rose from 28% in 2017 to 70% in 2020. “We can see there’s been a big shift,” Oskouei said.

According to the 2020 survey, 86% of oncologists said they would prescribe biosimilars in indications acceptable for extrapolation, vs 57% in 2019. In 2020, just 5% said they would extrapolate only for supportive care biosimilars. Oskouei stated that was “a pretty significant jump.”

In the 2020 survey, 72% said they would feel comfortable with switching patients from one biosimilar to another for the same condition. “That, again, highlights the sense of comfort that has developed with the FDA approval process and the scientific rigor that goes behind extrapolation and approving biosimilars as highly similar to reference biologics,” Oskouei said.

For more coverage of this year's ACCC meeting, click 

Survey results show that oncologists are embracing biosimilars not just in supportive care but for therapeutic uses also. 

Cardinal Health: Oncologists’ Comfort With Biosimilars Is on the Increase

At the Association for Community Cancer Centers’ 47th Annual Meeting & Cancer Center Business Summit (AMCCBS), we spoke with Lalan Wilfong, MD, a medical oncologist/hematologist and executive vice president of Value Based Care and Quality Programs. At the AMCCBS Virtual 2021 meeting, Dr Wilfong spoke about improving patient outcomes in cancer. We talked with him about the challenges of integrating biosimilars in a large network of physicians and how that was accomplished.

Videos

Lalan Wilfong, MD, an expert on value-based care, explains how Texas Oncology worked with physicians and payers to make biosimilars available for patients.

ACCC Virtual: Dr Wilfong of Texas Oncology Discusses Biosimilar Integration

During January 2021, The Center for Biosimilars® published findings from multiple studies that demonstrated the potential of biosimilars in the oncology space. Some of these results were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS) and the ASCO Gastrointestinal Cancers Symposium 2021 (ASCO GI). Also, the FDA initiated a review of a bevacizumab biosimilar candidate.

 a biologics license application for the review of Bio-Thera Solutions’ bevacizumab biosimilar candidate, BAT1706. The proposed biosimilar could become the third bevacizumab biosimilar to enter the US market, following Mvasi and Zirabev, which launched in July 2019 and January 2020, respectively, and together have achieved a 40% share of the US bevacizumab market.

Bio-Thera Solutions of Guangzhou, China, is seeking indications for metastatic colorectal cancer (mCRC), non–small cell lung cancer (NSCLC), glioblastoma, metastatic renal cell carcinoma, and metastatic cervical cancer. The company has also filed for regulatory approval in China and the European Union.

Additionally, a review evaluating the “totality of evidence” for Mvasi, an Amgen product, 

 no clinically meaningful differences between the biosimilar and the reference product, Genentech’s Avastin. The reviewers also concluded that historical data support extrapolation to all of Avastin’s indications. Mvasi is currently approved to treat mCRC, metastatic cervical cancer, and NSCLC.

During January, we reported more presentations from SABCS. One of studies we covered found 

 in Europe for the trastuzumab biosimilar Kanjinti among patients with metastatic breast cancer.

In the study, 28% of the sites analyzed had policies on biosimilar use and 36% of patients were informed they were being started on a biosimilar; of those, 34% were aware of what brand of biosimilar would be administered. Investigators said 40% of the patients switched to Kanjinti from another trastuzumab product, 44% switched from the intravenous form of the reference product, and 15% switched from the subcutaneous form.

 the biosimilarity of Viatris’ trastuzumab biosimilar Ogivri to the reference product. The data came from the HERITAGE randomized phase 3 trial, which previously demonstrated comparable efficacy and safety profiles between Ogivri and the originator, Herceptin, as frontline treatment for women with human epidermal growth factor receptor 2 positive advanced breast cancer. Ogivri launched on the US market in December 2019.

A retrospective study presented at ASCO GI demonstrated that 

 of Mvasi in the United States was strongest among patients with mCRC. Investigators also concluded that providers were comfortable initiating bevacizumab biosimilar treatment or switching patients to Mvasi. Patient characteristics and demographics were not significantly different between those switched from the reference product and those who initiated treatment with the biosimilar.

A separate study of Mvasi at ASCO GI demonstrated that physicians are 

 prescribing the biosimilar for patients with mCRC in accord with historical use of reverence bevacizumab. Evidence showed that the patient cohort that received first-line biosimilar treatment was similar in terms of demographics and clinical characteristics to the reference product cohort.

 on the incidence of hypertension and proteinuria in patients with gastrointestinal cancer treated with reference bevacizumab as opposed to biosimilars (Mvasi, Zirabev). A higher risk of hypertension was observed for the reference product cohort, but this was not statistically significant (

 = .2427). Additionally, hypertension was observed in patients after a median of 5 doses of the reference product vs 1.5 doses of bevacizumab biosimilar (

ASCO GI 

Findings from biosimilar studies of Kanjinti (trastuzumab) and Mvasi and Zirabev (bevacizumab) rounded out our oncology biosimilar coverage in January.

Oncology Biosimilar Roundup for January 2021

A retrospective, real-world study (N = 304) of the use of bevacizumab biosimilar (Mvasi, Amgen) in patients with metastatic colorectal cancer (mCRC) suggests physicians are comfortable prescribing the biosimilar in accord with historical use of the reference product (Avastin, Genentech), according to data presented at the 

ASCO Gastrointestinal Cancers Symposium 2021

Investigators based that conclusion on evidence that patients who received bevacizumab biosimilar in the first line of treatment for mCRC had demographic and clinical characteristics similar to those for patients treated with the reference product.

In addition, they said, among patients who had prior treatment with bevacizumab reference product (n = 162), most received the biosimilar in the first line of treatment within 28 days, which indicated the switch to biosimilar treatment occurred within the same line of therapy.

Bevacizumab is administered intravenously and works by starving tumors of nourishment by counteracting a protein (vascular endothelial growth factor) that enables tumors to develop blood vessels. Avastin was approved by the FDA in 2006 and European Medicines Agency (EMA) in 2009. 

 launched in July 2019 in the United States and was the first biosimilar to Avastin to gain FDA approval.

The biosimilar’s approval was based on a comparative clinical study in non-squamous non–small cell lung cancer, the researchers examined real-world use of bevacizumab biosimilar in mCRC, an approved indication they said is “lacking clinical trial data.”

They identified 304 eligible patients using a database of US electronic medical records from ConcertAI. The patients were adults with a diagnosis of mCRC who had been treated with bevacizumab biosimilar the first year after the product launch.

The respective divide between patients treated at community cancer centers as opposed to academic institutions was 86% vs 14%, respectively. Investigators said 57% of patients treated at community centers had prior bevacizumab compared with 31% of patients at academic centers.

Just over half (53%) of the entire patient cohort had previously received treatment with the reference product. The majority of patients received tumor-marking genetic tests and 53% of tumors had 

 mutations. The vast majority of tumors were negative for 

 mutations (92% and 86%, respectively). Microsatellite instability (MSI) and mismatch repair (MMR) testing indicated 93% of patients were MSI stable and 93% were MMR proficient.

Demographic characteristics and clinical characteristics, such as Eastern Cooperative Oncology Group performance status, tumor grade, comorbidities, and disease stage at diagnosis, were “comparable” between the 2 groups, according to the authors. Diabetes, chronic obstructive pulmonary disease, and renal disease were the most frequent comorbidities in both groups.

Investigators said 74% of patients who had prior bevacizumab treatment received bevacizumab biosimilar within 28 days of their last treatment with the reference product. Most (83%) experienced no disease progression between their last treatment with the reference product and starting treatment with bevacizumab biosimilar.

The study was conducted with Amgen funding.

DeClue RW, Rhodes W, Accortt NA, et al. Demographics and clinical characteristics of metastatic colorectal cancer patients treated with bevacizumab-awwb in real-world oncology clinics. Presented at: ASCO GI Cancers Symposium 2021; January 15-17, 2021. Accessed January 29, 2021. https://meetinglibrary.asco.org/record/194175/abstract

Investigators noted comparable use of bevacizumab biosimilar and reference products among patients treated for metastatic colorectal cancer (mCRC). 

Study: Bevacizumab Biosimilar Finds Acceptance in First-Line Treatment of mCRC

The past year was “turbulent” for the health care industry, and sales of Coherus BioSciences' pegfilgrastim product (Udenyca) were not what the company had hoped. But as the pandemic wanes, the company anticipates a change in market dynamics that will enable the product to achieve greater market share, according to Dennis M. Lanfear, president and CEO of the Redwood City, California, company.

Udenyca launched in 2019 and has achieved a roughly 20% share of the pegfilgrastim market, Lanfear said in a presentation at the 39th Annual JP Morgan Global Healthcare Conference. Coronavirus disease 2019 (COVID-19) gave a rival product a boost that denied Udenyca a greater share of the market it might otherwise have attained, he said. Pegfilgrastim is used to fight off infection associated with chemotherapy treatment. 

Amgen’s Neulasta Onpro on-body injector, launched in 2015, enables patients to receive pegfilgrastim injections at home, saving them from having to visit clinics battling to prevent the spread of COVID-19. By midyear 2020, Onpro had accumulated a 58% 

In his presentation at this year's virtual J.P. Morgan Health Care Care Conference, Lanfear predicted that vaccinations will enable patients to return to clinics for vaccinations and use of the Onpro will diminish, creating market opportunity for Udenyca. 

The chief value of Onpro is its convenience for home use, although a recent study recorded 

 from 1.7% to 6.9%. “We expect that as COVID-19 wanes, market gains at the expense of [the] Onpro share are expected to resume,” Lanfear said.

From its launch in January 2019 until September 30, 2020, Udenyca has achieved $720 million in revenues, Lanfear said. There are now 4 pegfilgrastim biosimilars on the market; most recently, Pfizer’s Nyvepria was launched in December 2020. Amgen’s originator pegfilgrastim products, including Onpro, control about 70% of the market. Although Lanfear predicted that Udenyca’s sales growth curve would point upward more sharply in 2021, he acknowledged the market power of the on-body injector and indicated that Coherus is working on its own version. He said it would be premature to share an anticipated market entry date.

In a discussion of the company’s biosimilar pipeline of products, Lanfear noted the company is developing versions of ranibizumab and aflibercept, both of which are for treatment of macular degeneration. Their respective originator brands are Lucentis and Eylea. The markets for each of these products are about $3 billion, Lanfear said.

Coherus is also developing a biosimilar to adalimumab (reference, Humira), which he said would likely enter the market in December 2023. The biologic is for treatment of rheumatologic and gastrointestinal disorders. Coherus submitted its biologics license application for FDA approval of its adalimumab biosimilar candidate (CHS-1420) at the end of 2020, and assuming regulatory approval, a 

The adalimumab market is changing, with providers starting to use citrate-free, high-concentration versions of this product, which may complicate marketing plans for Coherus and other biosimilar producers.

According to Lanfear, Humira achieved US sales of $15.9 billion in 2020. AbbVie, the originator company, has employed its exclusivity advantage to impose a steady stream of adalimumab price hikes. Humira prices have climbed 6-fold since 2005, according to Lanfear’s presentation.

“Relentless Humira price hikes and payer expense burden create a pent-up demand for biosimilar alternatives,” he said, predicting a “massive decoupling” ahead that would shift supply contracts to biosimilar manufacturers, once biosimilar versions of adalimumab become available in the United States, in 2023.

In a description of Coherus’ marketing strategy for leveraging greater biosimilar revenues, Lanfear said Coherus would target payers most of all, because they have the greatest control over what biologics are used by the health care community, relative to specialty pharmacies, providers, and patients. “We expect payers to have a significant share of power in selecting products and to drive share away from originators if properly incentivized.”

Coherus also has a bevacizumab biosimilar candidate (reference, Avastin) that it is developing in partnership with Innovent Biologics to submit for regulatory approval in the second half of 2021, Lanfear said. Bevacizumab is for the treatment of various types of cancer, including colorectal, lung, and kidney.

Annual J.P. Morgan Healthcare Conference

Coherus BioSciences CEO Dennis M. Lanfear discusses the company's biosimilar marketing prospects in 2021.

Coherus CEO Discusses Post–COVID-19 Growth Prospects

Results were inconclusive in a study of hypertension and proteinuria in 75 patients treated with bevacizumab reference vs biosimilar products, investigators reported at the ASCO Gastrointestinal Cancers Symposium 2021.

They compared incidence of hypertension and proteinuria in patients treated with various chemotherapy regimens in combination with bevacizumab. Investigators evaluated reference bevacizumab (Avastin) vs 2 biosimilars introduced on the US market starting in 2019: Mvasi, first marketed in July 2019, and Zirabev, first marketed in January 2020. The study period extended from January 2019 to July 2020 and enrolled patients with gastrointestinal cancer at Roswell Park Comprehensive Cancer Center at Buffalo, New York.

“Early recognition of uncontrolled blood pressures and worsening kidney function is needed to prevent delayed intervention,” investigators said, recommending routine monitoring of hypertension and proteinuria following treatment with bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody that targets the development of blood vessels that support the growth of tumors. Hypertension and proteinuria, which can lead to pulmonary edema and affects kidney health, are adverse events of bevacizumab.

Investigators noted a higher risk of hypertension in the reference bevacizumab group (52.4% vs 36.4%), although this was not statistically significant (

 = .2427). They observed hypertension in patients after a median of 5 doses of reference bevacizumab vs 1.5 doses of bevacizumab biosimilar (

Investigators observed a higher risk of proteinuria for patients treated with reference bevacizumab vs bevacizumab biosimilar (35.7% vs 30%), although this difference was not statistically significant (

 = .7193). However, proteinuria occurred later in the treatment cycle with reference bevacizumab than with bevacizumab biosimilar (median, 213 days vs 53.5 days following the first bevacizumab dose; 

Investigators concluded that the incidence of hypertension and proteinuria in patients treated with reference vs biosimilar bevacizumab requires study in larger patient cohorts.

Man Y, Yu H, Mukerjee S, Zalewski O. Incidence of hypertension and proteinuria in patients treated with bevacizumab versus bevacizumab biosimilar. Presented at ASCO GI Cancers Symposium 2021; January 15-17, 2021. Accessed January 19, 2021. 

https://meetinglibrary.asco.org/record/194106/abstract

The study was designed to elucidate incidence of hypertension and proteinuria in patients treated with bevacizumab reference vs biosimilar products. 

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