Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Frontline use of rituximab biosimilars plus chemotherapy in patients with follicular lymphoma (FL) is more costly than a regimen of obinutuzumab (Gazyva) plus chemotherapy, investigators reported, based on a decision-analytic modeling 

The study was conducted by assuming biosimilar rituximab agents were used in place of reference rituximab in the GALLIUM trial, which evaluated originator rituximab (Rituxan) vs obinutuzumab, both in conjunction with chemotherapy in the upfront setting. Rituximab is an older therapy, approved for first-line treatment of FL in 1997, and obinutuzumab was approved for advanced untreated FL in 2017.

provided evidence for longer progression-free survival (PFS) for patients with untreated, advanced FL who received the obinutuzumab regimen (G+chemo) vs the rituximab regimen, although grade 3-5 adverse events were more numerous with obinutuzumab. The 3-year PFS results from GALLIUM were 80.0% vs 73.3% for patients on G+chemo vs the rituximab regimen, respectively (HR 0.66; CI, 0.51-0.85; 

Investigators used GALLIUM as a model to evaluate potential savings and improvement in quality adjusted life years (QALY) for the rituximab biosimilars Truxima (Ra+chemo) and Ruxience (Rp+chemo). In the context of QALYs gained and cost savings that accrued from delayed disease progression, G+chemo proved to be the more cost-effective treatment, they said.

The model suggested that G+chemo would result in longer PFS and overall survival vs the rituximab biosimilar–based regimens 

. Although the overall cost of rituximab-biosimilar plus chemo options was less than for G+chemo, the incremental cost effectiveness ratio (ICER) for G+chemo was within commonly accepted thresholds for cost-effectiveness.

“Our results from the model indicate that G+chemo continues to offer good economic value, including improved patient outcomes, compared with R+chemo or equivalents based on rituximab biosimilars, and that value-based policy decisions should consider G+chemo as standard of care for patients with untreated FL,” the authors wrote.

A chief factor driving the cost-effectiveness outcome for G+chemo in GALLIUM was the “significant and clinically meaningful difference in PFS,” which the authors noted contributed to the additional QALYs deriving from use of this regimen.

Second, although the incremental costs of G+chemo vs Ra+chemo ($26,978) and Rp+chemo ($21,562) were higher, these differences were not high enough to undermine willingness to pay for the higher cost treatment, based on QALY thresholds. By contrast, in the original GALLIUM trial, the ICER for G+chemo vs the originator rituximab product plus chemo was $2300.

In addition, a cost savings of $7050 was attributed to the delay in disease progression afforded by G+chemo regimen.

Spencer SJ, Guzauskas GF, Felizzi F, et al. Cost-effectiveness of obinutuzumab versus rituximab biosimilars for previously untreated follicular lymphoma. 

. Published online February 17, 2021. doi:10.18553/jmcp.2021.20424.

Articles

Although a more costly medicine, obinutuzumab proved more cost-effective over the long run than rituximab biosimilars in follicular lymphoma.

Rituximab Biosimilar Regimen Fails Cost-Effectiveness Test in FL

Communicating the essentials of biosimilars to patients requires background knowledge and the right approach. These lower-cost agents have the potential to save money and improve access to care, but this can be of no avail if patients don’t get the information they need the way they want it.

Gary H. Lyman, MD, MPH, is an oncologist, hematologist, and public health researcher who has long been an advocate for biosimilars and, indeed, has developed guidelines in support of using these biologics for the treatment of cancer. In a recent interview, he shared his insights on conducting the patient-provider conversation about biosimilars and how physicians can prepare themselves to succeed with this encounter.

Lyman is co-director of the Hutchinson Institute for Cancer Outcomes Research in Seattle, Washington; a full member of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center; and a professor of medicine and medical oncology at the University of Washington. 

CfB: What’s missing from the patient-physician biosimilar conversation, and what are the essentials of communicating a patient’s biosimilar options successfully?

 I’m speaking primarily from an oncology perspective, but I’ve been involved with biosimilars from day 1. It’s important to focus on education and convince patients and providers about the enhanced regulatory process for molecular characterization, both structurally and functionally, of these agents. It’s far more sophisticated than it was 20 years ago when the first biologics were approved based largely on clinical comparative trial data. The FDA, and I’m in support of this, feels that there is sufficient depth of clinical data for demonstrating efficacy and safety once you fully characterize the molecule and its structural [and] functional characteristics and critical quality parameters. There are now dozens of these that the FDA is using to classify these biosimilars as highly similar to the originators.

Biosimilars get approved with data on pharmacokinetics, pharmacodynamics, and immunogenicity, and these trials are often done in patients with disease, but also in healthy volunteers, because at least in the oncology space, problems may not be as apparent in an immunocompromised patient who has been on chemotherapy or radiation therapy. Clinical comparative data are used to fill in any gaps of remaining uncertainty about the safety and efficacy of these agents to demonstrate that they are essentially the same as the originator molecules.

When talking with the patient, the challenge is to communicate a lot of this comfort with the regulatory process and the integration of biosimilars into treatment guidelines. ASCO has recently published an updated guideline in early stage breast cancer and [human epidermal growth factor receptor 2]–positive breast cancer that basically said the 5 approved trastuzumab biosimilars in the United States can be used equally or alternatively to the originator [Herceptin] without any concern about loss of efficacy and safety.

We have all that, and I communicate that to patients, along with my personal comfort with these biosimilars. But patients have many different levels of background and education, and the challenge is to communicate this information in a simple, nontechnical fashion. Many doctors don’t understand some of the terms, such as 

. Even if the doctor has a science background, communicating biosimilar information to patients in any kind of depth is going to be a big challenge. We’ve encouraged professional organizations and health systems to develop targeted educational materials, such as pamphlets, that summarize these points in lay language.

It’s also important to make clear that no major safety issues have been raised with biosimilars. There has been no withdrawal of agents from the market. We really need to reassure patients that the experience to date tells us that these are safe and efficacious. 

I do tell patients that biosimilars are approved with less clinical data than was used to approve the original agents, but those reference products were approved years ago when our technology was not nearly as good. Even so, there could be rare or delayed adverse events that emerge that you did not see in the limited clinical data used for biosimilar approval. I tell the patient, even if it seems unrelated to your treatment, let us know. We need to know if you’re having any unexpected symptoms or signs or concerns as time goes along.

Of course, the FDA is doing a lot of postmarketing surveillance of these agents. Each biosimilar is given a random 4-letter suffix that is used to track the performance of these products very closely. For Herceptin and the 5 approved biosimilars, you want to know which was given to the patient who developed a rash or some adverse event, and you can do that by being able to go back to the specific name and label given the biosimilar. But it’s traceable, and with the data capture, through patient-reported/physician-reported adverse events to the FDA, and just patients telling their doctor about problems, we hope that anything that’s slipped through inadvertently can be tracked and quickly pinned down if it has anything to do with the drug patients have received. Communicating all of this to the patient in a nontechnical fashion is a challenge.

One other issue is that biosimilars are biologic substances that cannot be reproduced exactly like a generic, and that’s one of the starting points I take with patients in communication. Biosimilars are not produced like generics in a test tube in the laboratory They’re produced in living systems like the originator biologic, and small differences will inevitably occur. And over time, there can be what we call drift in the structure and functional nature of these molecules.

Any small change in manufacturing, in the components that go into manufacturing these agents, could potentially change the molecular structure of these, although mostly this will not impact  the functionality or the toxicity of these agents. You cannot assume that automatically, so the FDA mandates that changes in components or processes of the biosimilars and originator products be reported and evaluated to make sure no critical aspect of the molecule has been changed. I think everybody’s very much attuned to making sure that we track these molecules, these biologic substances, over time to make sure they’re the same as the original.

It’s very difficult in a 15-minute office visit to communicate this level of information, and even physicians are not necessarily always comfortable explaining this, so I think having this information in nontechnical language, written out, simple and short, and then allowing patients an opportunity to look it over and ask any questions that they come up with is a really critical part of our communication, rather than just throwing out a whole lot of jargon very quickly, which causes them to glaze over. They may not want to ask questions or they won’t know what to ask.

CfB: Do you find that the literature that you’re provided for this purpose is adequate, clear, and helps to ease patients’ concerns?

We’ve developed some of our own, locally, and I know ASCO has, and I’m sure other professional organizations have done so, and they use outside observers, generally patient advocates or patients themselves to review it and validate the information or the conveyance of the information. I do think that, at least in many instances, due diligence has been done to make sure it’s comprehensive and understandable. That’s not to say it can’t be better.

I know that the Biosimilars Council and other organizations have worked on this as well. I think we all have the same goal: to make sure that patients fully understand about biosimilars and that they’re partners in this effort to improve access and reduce costs, but also to make sure safety and efficacy are maintained with these complex molecules. The information is available, but like anything else, it probably can continue to be improved over time—in particular, making sure that patients get their questions answered.

CfB: How are patients reacting? Are they throwing up their hands and saying, “Look, I just want to go with a brand drug. It’s so much easier”?

It can be a problem. As I said, patients come in all shapes and sizes and backgrounds. It ranges between 2 extremes, one being they don’t want to know anything. “Just tell me what to do, doc. Tell me what to take and I’ll do it. I don’t want to know too much about it.” At the other end, I’ve had patients come in with a whole laundry list of questions because they were told they were going to get a new drug. They come in and say, “Oh, you know, I need to know all this stuff.” Most patients want to know or at least be told. You may have to quiz them or ask a couple of targeted questions to make sure they’re comprehending, or just to reinforce.

Most patients are in that middle ground. They’re going to trust you. The most common question I get is, “Would you give this to your wife or your mother?” and I’m generally able to say “Absolutely. These are perfectly safe and effective.” You can’t put that into the pamphlet, but for most patients, if they have any questions, they’re probably going to be of that nature rather than the technical ones. They do want to know they’re not being sold a bill of goods and being given a drug purely because it’s cheaper. I and my colleagues feel the same way. We don’t want to use biosimilars just because they’re less expensive.

CfB: Is there enough information out there to convince providers that biosimilars are safe and efficacious? Are you satisfied with the FDA’s decisions on biosimilars, outright?

I am satisfied with the process, and the sophistication of the preclinical work that’s done is just light-years ahead of where things were when we approved Herceptin, Rituxan, Avastin, and many other original drugs. It’s just night and day, so that really reassures me. But given all that, I still am a strong believer in postmarketing surveillance, and the FDA has taken some recommendations from us and others to use big data for that. They‘ve engaged with CancerLinQ, the ASCO big data system. They’re working with Flatiron and other commercial big data suppliers.

I don’t think we can ever assume that because a study of 300 patients didn’t show some rare, serious, long-term adverse event, that it wouldn’t emerge when you have tens or thousands of patients taking this—often patients with more comorbidities than were included in the pivotal trials. As much as I’m comfortable with the process and the need to use biosimilars the way we’ve embraced them, it’s important not to let our guard down, and I think that’s reassuring to patients as well, to be able to tell them there are continuing efforts to monitor these agents very closely. 

CfB: Should you be completely honest with patients and tell them whether they’re getting a biosimilar or an originator?

I think you should. If you’re changing a patient from what they were getting, it’s absolutely crucial, because if you don’t, a nurse will tell them, or they’ll know from the bag, the prescription label, or the color of the medication. Or they’ll get a bill that mentions the drug that they’re taking. Trust is gold when it comes to communicating with patients. Otherwise they won’t be confident in your care.

Even when you’re starting a patient off on a biosimilar, it’s still worth the effort to explain, along with a brochure that details the process. And you should tell them that they can call any time if they have more questions, because you’re very comfortable that the treatments they are getting are as good as anything available for their disease. With only rare exceptions, you should be open and honest and tell the patient what they’re getting. If it’s a biosimilar, you can tell them that without spending an hour doing it.

CfB: What can doctors do if they feel they need more preparation for the conversation with patients about biosimilars?

It’s 3 words: education, education, education. There are a lot of education materials out there, but it’s such a rapidly changing area. Many biosimilars have come along already, and we can expect more in 2021. Keeping up with that is not an easy task, just like all of medicine. We’re in a biologics revolution. Generally, with targeted small molecules or biologics, continuing education is just absolutely at the core of being an oncologist these days, and it’s true for biosimilars as well.

I’ve been privileged to chair an ASCO task force on biosimilars in educating oncologists on biosimilars, and we’re in the process of updating our original statement paper. I believe there’s a substantial segment of the professional community, including my oncology colleagues, who have not looked at the issue as deeply as I wish they had. And it’s understandable. The rate of change we are talking about here is not just biosimilars; it’s all of biologics itself—cancer, therapeutics, diagnostics, molecular testing, and so forth. I think we’re all kind of struggling with how do we attract that 50%, or maybe it’s even more, of oncologists who haven’t really dived in and fully educated themselves on biosimilars such that they can discuss them with comfort and reassurance to their patients.

Gary H. Lyman, MD, PhD, provides an expert overview on overcoming the challenges of discussing biosimilars with patients.  

Filling in the Blanks: The Patient-Provider Conversation About Biosimilars

Fresenius Kabi has launched an adalimumab injectable biosimilar (Idacio) in Canada, the company said in a 

. The product, which marks Fresenius Kabi’s first North American biosimilar launch, is approved for all 12 indications of the reference product, Humira, in Canada.

Those indications are rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, adult and adolescent hidradenitis suppurativa, adult and pediatric Crohn disease, ulcerative colitis, adult noninfectious uveitis, and pediatric chronic noninfectious anterior uveitis. Health Canada issued approval for the biosimilar on October 30, 2020.

Fresenius Kabi’s global headquarters are in Bad Homburg, Germany, although it operates a Canada division that is managing this launch.

The Canada launch marks the second for an adalimumab biosimilar this week. Sandoz 

 Hyrimoz, also an injectable biosimilar, which is indicated for 9 of 12 indications of the originator product.

Idacio has been available in Europe since 2019, although in a low-concentration formulation that faces strong competition from other adalimumab biosimilars and a high-concentration version of adalimumab introduced by AbbVie, the originator company.

In its pipeline, Fresenius Kabi is developing a tocilizumab biosimilar, referencing Actemra, which is for the treatment of severe rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. The company also is developing a pegfilgrastim biosimilar, a supportive care product for the treatment of patients undergoing chemotherapy and vulnerable to infection.

Canada is considered an increasingly fertile territory for biosimilar distribution, given the country's embrace of these lower-cost medicines through the development of policies that give preference to biosimilar use. Earlier this month, Celltrion received Health Canada 

 for a subcutaneous infliximab biosimilar (Remsima) for the treatment of rheumatoid arthritis.

Also, in November, Alberta, the fourth largest province in Canada, reported early success with a 

. According to Graham Statt, assistant deputy minister of the Pharmaceutical and Supplementary Benefits Division for Alberta Health, 30% of patients receiving infliximab in Alberta had switched to a biosimilar since December 2019. And in general, the province had succeeded in switching 16% of patients from 7 costlier reference products. Alberta is aiming for biosimilar savings approaching $200 million over the next 4 years.

Fresenius Kabi steps into the Canadian market for adalimumab with Idacio.

Canada Sees Second Adalimumab Biosimilar Launch in a Week

Coherus BioSciences reported that the FDA has 

 for review its biologics license application (BLA) for an adalimumab biosimilar (CHS-1420). The formulation concentration Coherus is seeking was not specified, although the market is swiftly moving away from lower-concentration forms of this agent.

In 2017, the Redwood City, California, company reported topline results from ongoing pharmacokinetic (PK) bioequivalence studies that compared CHS-1420 with a European-marketed version of the reference product (Humira). The company reported that the comparison was based on administration of a 40-mg dose in a group of 216 healthy patients, a trial that met all end points for clinical PK and pharmacodynamic biosimilarity.

By comparison in November, Icelandic company Alvotech indicated that the FDA had 

 its application for a 100-mg/mL dose biosimilar (AVT02). However, Alvotech’s supporting data for the application involved a phase 1 PK similarity study that employed a 40-mg single dose of Humira in healthy subjects and a phase 3 safety and efficacy study that employed an initial loading dose of 80 mg followed by 40 mg every 2 weeks.

In 2016, Coherus reported results from a phase 3 psoriasis study of CHS-1420 that were also positive, demonstrating biosimilarity in patients who achieved a 75% improvement in psoriasis area and severity index measures at week 12. Coherus said CHS-1420 and Humira were “similarly well tolerated with similar safety profiles.” This phase 3 study was intended to support a 351(k) BLA filing in 2017, although that filing was delayed; the company had hoped to achieve a filing by the end of 2020, according to its third-quarter 2020 

Coherus said in its most recent statement that it intends to launch its adalimumab biosimilar in the United States on or after July 1, 2023, under terms agreed upon with AbbVie.

“We are pleased to see the CHS-1420 BLA accepted for review, as we continue to execute on our mission to increase patient access to important medicines and deliver substantial savings to the health care system,” said Denny Lanfear, CEO of Coherus. The company said it anticipates that the US market for adalimumab will be worth $18 billion annually by 2023, representing “substantial pent-up demand” for biosimilar products.

If Coherus brings a low-concentration form of adalimumab to market in 2023, the market may still exist for this version of the blockbuster medication, as competitive pricing may in some cases overcome any disposition on the part of physicians to prefer the higher concentration formulation.

Coherus BioSciences filed a 351(k) biologics license application (BLA) for CHS-1420, an adalimumab biosimilar candidate. 

Coherus Files Adalimumab BLA, Although Intended Concentration Is Unclear

 low-concentration forms of an adalimumab injectable biosimilar (Hyrimoz), which is indicated for 9 of the 12 conditions of the originator product (Humira), including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn disease, ulcerative colitis, hidradenitis suppurativa, psoriasis, and adult uveitis.

As of late 2020, Health Canada had approved 35 biosimilars for marketing in the country, according to Sandoz. Grassroots efforts by regulators and health authorities in provinces and territories of Canada are rapidly advancing the use of biosimilars as a cost-savings measure and to free capital for the expansion of care to serve other needs. 

The Ontario Drug Policy Research Network 

 that nonmedical and mandatory switching policies in all provinces for etanercept and infliximab biosimilars could have generated $239.6 million in national savings in 2019. The market for adalimumab in Canada is estimated at 42,000 patients.

Adalimumab is a tumor necrosis factor blocker that reduces inflammation. Sandoz said the product will be offered in 40-mg/0.8 mL and 20-mg/0.4mL doses in single-use prefilled syringes and in a 40-mg/0.8 mL dose in the SensoReady pen autoinjector, designed for patients with limited dexterity.

Authorization for the marketing of Hyrimoz was issued by Health Canada in December 2020. The approval marked the fourth biosimilar approval in Canada in 11 months for Sandoz, whose biosimilars portfolio in Canada now encompasses oncology, immunology, and endocrinology products.

Sandoz said the Hyrimoz launch will be supported by a patient support program to aid with reimbursement navigation, financial assistance, administrative support, and education about the use of biosimilars.

For more information about adalimumab biosimilars and market trends, click 

The launch of Hyrimoz gives Sandoz 5 biosimilars on the Canadian market. National policies on switching have given biosimilars a tailwind.

Sandoz Launches Adalimumab Biosimilar in Canada

Celltrion Healthcare has gained EU marketing authorization for the first high-concentration, citrate-free adalimumab biosimilar, the company said. The company has chosen the brand name Yuflyma for the product, which was referred to as CT-P17 during drug development.

The approval is significant because although the European market already has various adalimumab biosimilars, these are lower volume and contain citrate, which is known to make the administration process painful for patients. In addition, AbbVie, the originator company, has managed to achieve a 60% share of the highly lucrative adalimumab market with its own high-concentration, citrate-free version of adalimumab, so the market is evolving away from the lower-concentration forms, according to the IQVIA Institute for Human Data Science. 

Celltrion’s approval gives it the opportunity to be the first to compete in this new market with a lower-cost biosimilar, although the company did not indicate in its press statement the depth of the pricing discount or discounts that would be offered in the European market.

Other advantages of the product are its small or "ultra-fine" needle size, 29 gauge, its latex-free application, and its shelf life of up to 24 months. At room temperature, the biosimilar is stable for up to 30 days, Celltrion said.

“With high concentration, low-volume, and consequently less pain, adalimumab can improve treatment adherence at the very least,” Celltrion said HoUng Kim, PhD, head of the Medical and Marketing Division at Celltrion.

The biosimilar was approved for patients with 13 chronic inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, pediatric plaque psoriasis, ulcerative colitis, and Crohn disease in both adults and children.

In a statement accompanying the company’s news announcement, a professor of medicine praised the biosimilar as an advantage enabling providers to offer patients a reduction in injection discomfort. “Over the past 2 decades, anti-tumor necrosis factor (TNF) biologics have revolutionized the management of chronic immune-mediated inflammatory diseases, but some of the features needed improvement,” said Professor Rieke Alten, head of the Department of Internal Medicine, Rheumatology, Clinical Immunology, and Osteology at Schlosspark-Klinik Teaching Hospital of Charite, Berlin, German.

Celltrion aims to take advantage of a rapid approval procedure to get Yuflyma approved in the United Kingdom. The European Commission Decision Reliance Procedure enables automatic submission for UK regulatory approval following EU authorization.

The company said it received EU marketing authorization for Yuflyma based on clinical, preclinical, and analytical studies that demonstrated the biosimilar is comparable to Humira, the reference product, in terms of safety, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity up to 24 weeks 1 and 1 year following treatment.

Yuflyma is not yet approved in the United States, where there are currently no adalimumab biosimilars on the market. 

For a recent interview with Kim about Yuflyma, click 

The marketing of Yuflyma is expected to give Celltrion Healthcare a significant advantage over existing adalimumab biosimilars.

Celltrion Healthcare Gains EU Authorization for High-Concentration Adalimumab

Patients’ demographics and physiological characteristics influence whether they will accept a switch from an originator drug to a biosimilar, according to findings from a New Zealand study.

For example, being a woman was a strong predictor of concern about a biosimilar switch (

< .001), they said. “Gender was significantly correlated with perceptions of a biosimilar's safety. Female patients were more concerned about switching from a bio-originator to a biosimilar [

Patients who perceived they are highly sensitive to medicines were less likely to accept a biosimilar switch (

= .001), and those with a habit of looking health information up on the internet were more likely to be concerned about switching (

In addition, patients who had strong emotional responses to their health condition were less likely to perceive biosimilars as safe or to consider switching from originator drugs, although these findings were not statistically significant.

Investigators enrolled 96 patients taking originator drugs for rheumatic diseases. Patients were asked to watch a video tutorial explaining biosimilars and their equivalence to originator drugs and then given a survey to gauge their receptiveness to biosimilars.

The average patient was aged 54 years and college educated (64%); most were women (69%). The most common originator therapy was rituximab (35%), and the most frequent condition rheumatoid arthritis (65%).

A strong negative association for biosimilar safety was observed among those who had taken the originator product for only a short time (

The investigators said their findings were consistent with previous studies. “Interestingly, the study findings show that concerns about switching to a biosimilar are exacerbated in patients who have stronger emotional responses to their condition. This is an important finding as negative affective responses, such as anger or fear, are common in patients with arthritis but can bias treatment decision-making and risk perceptions.”

They added that the finding about strong emotions and biosimilar rejection suggests that efforts to improve patient coping skills and resilience may pay off.

Past studies also have shown that patients with high levels of health anxiety and perceived sensitivity to medicines tend to search for information online. One concern is patients may access incorrect information. Providers should step in after a switching discussion with “credible material” to help support the switch, the authors said.

A patient’s experience with the originator product, in terms of effectiveness and adverse events, is also a factor in biosimilar acceptance. Providers need to “assess and reassure patients who have had unfavorable experiences with biosimilars,” the investigators said.

The study was important because biosimilars are equivalent to originators in terms of safety and efficacy, and they have the potential to bring down the costs of health care. Knowing which patients are less likely to be accepting of a switch to a biosimilar can allow for interventions, the investigators said. 

Gasteiger C, Lobo M, Dalbeth N, Petrie KJ. Patients’ beliefs and behaviors are associated with perceptions of safety and concerns in a hypothetical biosimilar switch. 

. Published online April 16, 2020. doi:10.1007/s00296-020-04576-7

Patient characteristics are predictive of whether a switch to a biosimilar is likely to be accepted, investigators found. 

Study: Gender, Internet Habits Influence Biosimilar Acceptance

Sifting through the rubble of the pandemic, there are many lessons to be learned in how to make innovation work, said an 

 of government and industry experts convened by Amgen.

Innovation doesn’t always work by itself to put medicine into the hands of those who need it. Government had to step in to get the vaccine development process started, and bureaucratic obstacles had to be cleared away. What has been learned so far will probably be retained to improve the process going forward and lead to a more global approach to solving problems on this scale, the panelists said.

“It’s an interesting health crisis, where the cost of inaction has been so obvious,” said Anne Marie Morris, chair of the All-Party Parliamentary Group on Access to Medicines and Medical Devices in the United Kingdom. “Often with health care, you don’t see any cost of inaction. It’s a person who is ill who dies. Nobody else cares, only their family. Whereas, this time, we saw what happens when systems were slow or rigid. People didn’t get their vaccines, and communities had to stay on lockdown. It turned out to be penny wise, pound foolish.”

To be sure, many positives have emerged during the pandemic. Among them is the digitization trend in health care that has involved patients researching their own health needs and treatment options. This has been accelerated by coronavirus disease 2019 (COVID-19), as evidenced by the momentum gains that biosimilars have achieved in the past year, said panelist Christophe Bourdon, senior vice president and general manager of US Oncology Business for Amgen.

There are challenges ahead, given recent predictions that deficiencies in screening and testing could lead to more COVID-19–related deaths, but keeping down the cost of medicine can free up capital for investing in solving problems like this, Bourdon said. “Innovation is a solution. The question is going to be how to make sure that we can bring more innovation faster, so we can generate some savings to reinvest to generate additional innovation. That’s going to be one of the critical questions for governments and payers in the years to come.”

Innovation practiced over the past year has taken the form of workarounds that have enabled health care institutions and practices to deliver care despite the challenges of treating patients safely amid the pandemic, said Murray Aitken, executive director of the IQVIA Institute for Human Data Science, another panelist. “That to me speaks to the innovative approaches that have been taken by multiple stakeholders to try to get things back on track as much as possible.”

What was telling about the way vaccines and other treatments for COVID-19 were developed over the past year was that government was involved, said Anthony A. Barruera, senior vice president of government relations for Kaiser Foundation Health Plan, Inc and Hospitals. “The pharmaceutical system has really lavishly funded innovation in the pharmaceutical sector over the past several decades, and there’s a question about whether it’s efficient and whether it’s appropriately broad around the conditions that need to be treated,” Barruera said. “It’s also important to realize that they were not financed through the usual system of pharmaceutical finance. It was largely financed by government direct funding, admittedly on top of a system that exists because of what’s been built up over the past couple decades. But it’s telling what’s possible.”

But when it comes to innovation, especially with biosimilars, it’s important to build physician and patient confidence and trust to support uptake, he said. “You need to have very strong data to make sure that you’ve got the clinical support by the physicians who are using the products, and this is something that our medical groups and our pharmacists have studied intensely. When this level of data has been combined with biosimilar availability, uptake for Kaiser Permanente has soared as high as 95%.”

Trust is an important matter for vaccinating populations because people tend to be wary of vaccines, the panel noted. “I think the key of government to build that is to be as open and honest as they can be about what’s going on,” Morris said. “That’s not that easy. I think certainly in the United Kingdom, Boris Johnson has taken us through what’s happening step by step.”

The United Kingdom managed to get a vaccine approved before the European Medicines Agency, which led to concerns that there had been shortcuts and compromises on quality. That wasn’t true, Morris said. What really happened was that a lot of inefficient debate that contributed nothing to the development and approval of vaccines was eliminated from the process, and “the consequence was that decisions were able to be made faster.” This, she said, is probably the beginning of a reduction of bureaucracy in how medicines are developed and approved.

The different pace at which international regulatory bodies reach their decisions about vaccines, using basically the same data, is concerning, the panelists agreed. “The timing of their assessments is quite different, and in the context of this pandemic, we now recognize that those differences have real consequences, in terms of lives and in terms of the number of people who can be vaccinated, so I think this is going to trigger a broad rethink about the effective ways to access and look at data and then harness the full value,” Aitken said.

Another disturbing revelation that has emerged from the pandemic is how vulnerable the United States was because of its reliance on a fee-for-service revenue system in the medical industry, Barruera said. “This notion that a massive, immediate economic bailout was necessary to keep the medical system afloat in the short term shocked everyone, and there’s a growing appreciation for the need to be in more of a prepaid, value-based-compensation kind of environment where organizations can take a longer view, have greater stability, and build for the populations that they’re serving. But it’s going to take us a while, I think.”

One challenge for all stakeholders is getting innovative products to the populations who need them, said Bourdon. “We all see the cracks in the system at the moment.” In some cases, minorities have had less access to COVID-19 vaccines. “I’m a firm believer that innovation will be accepted by society if we are bringing the right innovation to the right patient.” Amgen recently signed a partnership deal with Intermountain Healthcare to develop genetic profiles of a large number of individuals to aid in developing medicines, and this could serve the purpose of individualized medicine, he said.

Other innovation could take the form of corporations building better relationships with their suppliers so that information can be exchanged more openly, Morris said, citing the experience of Ford Motor Company. “They found that what they needed was excellent relationships with their suppliers so that when factories were closed, or whatever, they were able to lend them money, extend credit, help them to get back on their feet, which you wouldn’t do unless you had relationships.” Although this sounds like a one-way relationship with the suppliers gaining all the benefit, Ford was able to obtain data, visibility, and trust, she said. The implication is that better relations between pharmaceutical companies and their suppliers could help avert supply chain breakdowns, which have been an issue during COVID-19.

Biosimilars, supply chain adjustments, building trust, and international standardization were discussed as means to deliver innovation when it's needed, not after. 

Amgen Panel Tackles Lessons From Pandemic

Lannett of Trevose, Pennsylvania, is aiming for a share of the estimated $6 billion market for insulin aspart in a 

 to develop a biosimilar with HEC Pharm of China. HEC will handle the manufacturing preparations and some of the clinical development work and Lannett will fund and manage clinical and regulatory steps for FDA approval.

Insulin aspart is a fast-acting insulin used for the treatment of type 1 and type 2 diabetes in adults. There are various products on the market, but one of the leaders is NovoLog, a NovoNordisk brand.

Lannet, traditionally a generics developer and distributor, and HEC Pharm, which has an extensive sales network in China, also are developing a biosimilar to insulin glargine, a long-acting insulin. Long-acting insulin peaks in the bloodstream later and remains active for significantly longer than short-acting insulin.

In June 2020, Lannett approached the FDA to present clinical, chemistry, manufacturing, and control data for the insulin glargine biosimilar candidate and reported that the meeting was positive and productive. The company hopes to file a 351(k) biosimilar application with the FDA in 2022. HEC Pharm is also a partner in this effort.

Insulin products were only recently added to the list of proteins that can be approved as biosimilars under the Biologics Price Innovation and Competition Act (BPCIA). The March 2020 change was done in part to spur the development of a competitive insulin market that would bring down prices and improve access for patients. So far, no insulin products have been approved under the BPCIA.

Mylan and Biocon Biologics in June 2020 received FDA approval for an insulin glargine (Semglee) referencing Lantus (Sanofi), but under a different regulatory pathway, so the product is not technically a biosimilar. However, the companies said at the time of approval that they intend to file for an official 

Lannett CEO Tim Crew said the company’s development of an insulin glargine biosimilar is about a year ahead of the insulin aspart effort. “Biosimilar insulin aspart is a significant opportunity for us and adds another large, durable, and complementary product to our development portfolio.”

Lannett and HEC Pharm are developing an insulin aspart biosimilar on the heels of their insulin glargine codevelopment project.

Lannett, HEC Pharm Team Up on Insulin Aspart Biosimilar Project

on the Supreme Court case involving the severability of the individual mandate from the Affordable Care Act (ACA), now arguing that the ACA should not be struck down if the mandate is deemed unconstitutional.

Under the Trump administration, the DOJ argued the mandate was not severable, but under President Joseph Biden the federal argument is now different. Oral statements were held before the Supreme Court in November 2020 whether the entire ACA should be invalidated. A decision is expected in June. 

The Trump administration had sided with Republican-governed states led by Texas that had argued against severability and for the invalidation of the ACA.

The significance for biosimilar markets is that if the ACA is allowed to stand, the biosimilar regulatory approval pathway, or Biologics Price Innovation and Competition Act, which is part of the ACA, will remain also.

The DOJ position was outlined in a letter filed by Deputy Solicitor General Edwin S. Kneedler. “The purpose of this letter is to notify the court that the United States no longer adheres to the conclusions in the previously filed brief of the federal respondents,” Kneedler wrote. “After reconsideration of the issue, it is now the position of the United States that the amended Section 5000A [individual mandate] is constitutional.”

The individual mandate was amended so that individuals do not have to pay a penalty if they do not have coverage for themselves.

Kneedler went on to say that if the Supreme Court decides that the altered section is unconstitutional, it is the DOJ position “that provision is severable from the remainder of the ACA.”

The Biden administration has promised to strengthen Obamacare by improving access to coverage and medical care for residents of the United States.

Under the Biden administration, the Department of Justice (DOJ) has reversed course and now backs the constitutionality of the Affordable Care Act (ACA).