Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

 their biologics license application (BLA) for a ranibizumab biosimilar candidate. A resubmission became necessary in early 2020 after the FDA asked for more information about the manufacturing process involved in producing the biosimilar candidate, which would be used for the treatment of macular degeneration.

The biosimilar candidate (FYB201) would reference Lucentis. In a previous 

 on the regulatory review process, Formycon and Bioeq explained that some processing equipment had been shifted to a different location in compliance with a request from European Union health authorities. Subtle changes in manufacturing process can affect the quality of biologics, although Formycon and Bioeq stated last year that the manufacturing change did not affect product quality or other product characteristics. Their BLA was withdrawn while they compiled the additional data requested by the FDA.

In their November 2020 update, the companies said they had hoped to resubmit their BLA in the first half of 2021 and did not anticipate that the resubmission process would change their timing for the launch of FYB201 in the United States or the European Union.

A mid-2022 FDA decision is anticipated on the application, according to Coherus BioSciences, which will serve as a US distribution partner in the commercialization effort, based on a 2019 agreement. Coherus is anticipating a launch on or after 

, if the ranibizumab biosimilar candidate is approved.

Ranibizumab is used in the treatment of wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy, myopic choroidal neovascularization, and macular edema following retinal vein occlusion.

In its second quarter earnings report issued this week, Coherus said its adalimumab biosimilar candidate (CHS-1420) remains under FDA review for approval and a December decision from that regulatory agency is anticipated.

Udenyca is the company’s sole current source of revenues, and Coherus reported net revenue of $87.6 million from second quarter 2021 sales of the pegfilgrastim biosimilar, although the company’s heavy investment in research and development and its regulatory licensing expense drove it to a loss of $29.9 million for the quarter. The comparable figures for the year-ago quarter were $135.7 million in Udenyca revenues and a net profit of $59.0 million.

Coherus also has a biosimilar bevacizumab candidate (CHS-305) under development in collaboration with Innovent Biologics. A pharmacokinetic study is underway to support a planned BLA application.

Articles

After a delay caused by a manufacturing shift, Formycon and Bioeq are back on track with their ranibizumab biologics license application (BLA), and their partner Coherus BioSciences is aligned for US commercialization. 

Formycon and Bioeq Update on Ranibizumab BLA, and Coherus Reports Earnings

 $557 million in biosimilar revenues for the second quarter of 2021, up 56% from $357 million this time this year, saying growth was driven by higher sales, offset somewhat by price declines. Competition among biosimilars and originator products is driving down prices at the overall rate of 10% to 15% per year, Amgen has previously 

“For the remainder of the year, we expect worldwide biosimilar volume growth to be offset by declines in net selling price due to increased competition,” Murdo Gordon, executive vice president of Global Commercial Operations for Amgen, said in an investor conference following release of the second quarter results.

Total corporate revenues for the quarter just ended, including all nonbiosimilar product lines, were $6.53 billion, up 5%. For this past quarter compared with the comparable 2020 quarter, the company reported a 74% decline in net income ($464 million vs $1803 million), based on generally accepted accounting principles, which it said was largely due to a write-off associated with an acquisition. 

The company expects further biosimilar sales growth sales to come from sales of existing products in new markets, along with launches of new biosimilars to compete with eculizumab (Soliris; Alexion), ustekinumab (Stelara; Janssen Biotech), and aflibercept (Eylea; Regeneron) originator products. Amgen has biosimilar candidates in phase 3 trials for each of these products.

Murdo said Amgen is also banking on sales of its adalimumab biosimilar (Amgevita) once it enters the US market in 2023. The product received FDA approval in 2016 but has been delayed US market entry owing to patents held by AbbVie, the originator (Humira) owner, and a settlement with AbbVie under which the companies agreed on delayed US entry.

A wrinkle in this picture is that rival companies (Celltrion, Alvotech) are aiming to capture adalimumab market share with a high concentration version of the drug that has been gaining ground in both the United States and Europe. These versions of adalimumab, if they are not held back by AbbVie’s patent protections, could pose competitive problems for the lower-concentration Amgen biosimilar.

Amgevita was approved by the European Medicines Agency in January 2017, and Amgen reported a 73% increase in second quarter sales vs the comparable 2020 period ($107 million vs $62 million). “Amgevita continued to be the most prescribed adalimumab biosimilar in Europe,” the company said.

Sales of the company’s pegfilgrastim (Neulasta) wearable injector kit (Onpro) declined 18% compared with the comparable 2020 second quarter ($486 million vs $593 million) and the average US selling price for Neulasta declined 35% when comparing second quarter 2021 performance with the year-ago quarter and 12% when comparing the second quarter 2021 sales with first quarter 2021 sales. “We expect this trend will continue throughout 2021 driven by intensifying competition,” Murdo said.

Sales of the company’s originator etanercept product (Enbrel) dropped 8% compared with this time last year ($1.14 billion vs $1.25 billion), and the company again blamed lower selling prices for this. So far, Enbrel faces no competition in the US from biosimilars but has 3 biosimilar competitors in the European Union.

Sales of the company’s bevacizumab (Mvasi) biosimilar were up 71% ($294 million vs $172 million). Sales of the trastuzumab biosimilar Kanjinti were up 27% from last year ($156 million vs $123 million), and this product has a 42% share of the market for trastuzumab, Amgen said.

The company said sales of its epoetin alfa (Epogen) originator product, which faces biosimilar competition in the United States and European Union, were down 19% for the year ($130 million vs $161 million), based on declines in selling price and lower unit sales.

Amgen reported a strong increase in biosimilar sales for the year but said competition is forcing down prices and affecting revenues for its originator products, too. 

Amgen Reports 56% Increase in Biosimilar Sales

The American Academy of Ophthalmology (AAO) is protesting payer policies that recommend biosimilars be used for the treatment of certain ophthalmologic diseases, on grounds that more clinical testing is needed and one of the biosimilars in question may be toxic to the retina.

The originator drug Avastin (bevacizumab) is used off label currently for treatment of wet age-related macular degeneration (AMD) and involves an injection into the eye, and it is currently the price-competitive alternative for ranibizumab (Lucentis) and aflibercept (Eylea).

In the United States there are no biosimilars for ranibizumab or aflibercept available, although there are biosimilar versions of bevacizumab.

“Insurance companies are pushing ophthalmologists to use new biosimilar drugs as alternatives to Avastin that have never been tested in the eye, essentially making patients who depend on this commonly used drug unwitting subjects in a clinical experiment,” the AAO said in a 

Biosimilars are approved by the FDA as being highly similar in terms of safety and efficacy, with no clinically meaningful differences, to originator drugs. Although the FDA has not specifically indicated Avastin for ophthalmologic disease, the AAO says there is sufficient clinical evidence that Avastin is safe and effective in the treatment of AMD, macular edema, and neovascular glaucoma, among other diseases.

The group contends there ought to be separate testing of biosimilar bevacizumabs to verify that they work equally well in eye disease. Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor, which works by preventing the abnormal growth of blood vessels that can damage the eye or harm vision.

A supply shortage of Avastin, caused by a production line overhaul, has pushed this issue to the forefront, the AAO says. Commercial payers, it says, are unwisely recommending that providers use the 2 available bevacizumab biosimilars on the market: Zirabev (Pfizer) and Mvasi (Amgen).

The Academy does not oppose the use of biosimilars or the use of drugs off-label in general. We are against the use of drugs in the eye that have 

“Avastin is also an anti-VEGF medication; however, its use in the eye is supported by clinical evidence. The newer, biosimilar drugs have never been tested in the eye,” the group said.

One of those biosimilars, Zirabev, is manufactured with edetate disodium dihydrate (EDTA), a buffering agent that the AAO says has shown to be toxic to corneal and conjunctival epithelial cells. “Potential retinal toxicity of EDTA has not been studied,” it notes.

Aetna is among the payers that are recommending bevacizumab biosimilars in place of more costly VEGF inhibitors.

“There is a lack of reliable evidence that Lucentis and Eylea are superior to the lower cost VEGF inhibitors,” Aetna says in a 

 updated June 3, 2021. Aetna names Avastin, Mvasi, and Zirabev as equivalent treatments for macular edema, AMD, and various other eye conditions, including diabetic retinopathy and myopic choroidal neovascularization.

The AAO also names CareFirst, United Healthcare, Humana, Horizon Blue Cross Blue Shield of New Jersey, AmeriHealth, and Health Assurance Pennsylvania as other payers that are supporting the use of biosimilars for ophthalmologic conditions.

“The [AAO] has told HHS and CMS it is inappropriate for plans to recommend or mandate use of these biosimilars for intravitreal injection without a prior clinical trial in eye disease and testing for retinal toxicity,” the group’s statement said.

The experience in oncology could be instructive for the use of biosimilars in ophthalmology, said Neal Dave, PharmD, executive director of pharmacy for Texas Oncology. Biosimilars have been a positive experience and excluding biosimilars from ophthalmology solely on the basis of being biosimilars wouldn’t be logical, he said.

“Whether it’s indicated or not, we know that bevacizumab works in macular degeneration,” he said. “The trepidation for using biosimilars in ophthalmology is similar to what we felt in oncology, but there haven’t been any issues.”

For an informative Cardinal Health column on the biosimilar pipeline in ophthalmology, click 

A supply chain shortage of Avastin (bevacizumab) is prompting policies for use of bevacizumab biosimilars instead, which the American Academy of Ophthalmology says could lead to problems.

Ophthalmology Group Opposes Payer Recommendations for Bevacizumab Biosimilars

The Republic of Korea’s might as a pharmaceutical producer continues to grow. The country’s Ministry of Food and Drug Safety reported a 62.5% surge in exports of medicine in 2020 to $8.7 billion, according to the 

The top 3 drugs among exported Korean pharmaceutical products were all biosimilars produced by Celltrion: Remsima (infliximab), $473 million; Herzuma (trastuzumab), $85.8 million; Truxima (rituximab), $65.5 million. These agents are used in the treatment of rheumatoid arthritis, breast and gastric cancer, and arthritis and lymphoma, respectively.

The top 3 international importers of Korean drugs were Germany ($1.85 billion), United States ($780 million), and Turkey ($589 million), according to the 

Eight biosimilar products produced in Korea were among the top 20 drugs exported in 2020.

The top 10 companies producing drugs in Korea in 2020 were Celltrion, whose output surged 149.2%, Hanmi Pharmaceutical, Chong Kun Dang, GC Pharma, inno.N, Daewoong Pharmaceutical, Yuhan, LG Chem, Dong-A ST, and JW Pharmaceutical. Almost all of these companies are involved in the production or distribution of biosimilars. 

Hanmi has a heavy emphasis on insulin products. The company produced $992 million in medicines in 2020.

Celltrion said Tuesday, August 3, 2021, that it 

 to market Herzuma and Truxima in Brazil following a successful bid to Brazil’s ministry of health. The company said it would supply trastuzumab to the public market, which accounts for 80% of trastuzumab demand in the country. Celltrion said that so far this year, it has won 8 state bids for supplying rituximab, including one in Sao Paulo, which it said is one of the largest state contracts.

“There is a great demand to substitute expensive original pharmaceuticals with biosimilar drugs with proven safety and efficacy to reduce health care costs in Central and South America,” said HoUng Kim, PhD, head of the Medical and Marketing Division at Celltrion. “We are excited to win one of the most important bids in Brazil for 2 consecutive years and will continue to expand our presence in the Central and Southern American market with our anticancer biosimilar products.”

In March 2021, Celltrion began direct sales of infliximab biosimilar in Colombia and is beginning to market rituximab and trastuzumab biosimilars there this summer. The company also plans to sell biosimilars in Peru and Chile starting in the third quarter of this year.

for further reading on Celltrion's growing investment in biopharmaceutical production. 

for an article about Republic of Korea's 2019 pharmaceutical production and exports. 

When it comes to exports, Celltrion Healthcare leads the way among Republic of Korea pharmaceuticals producers. The company's biosimilars are the leading exports.

Celltrion Dominates Republic of Korea Drug Exports, Targets Latin America

Biocon Biologic's Semglee insulin glargine as an interchangeable biosimilar, referencing Lantus. The approval carries with it many hopes for stronger competition in the insulin market, which is dominated by a handful of brands and characterized by stubbornly high prices. 

The approval of Semglee was much anticipated; it is also the first biosimilar decision for the year, during which the FDA has been preoccupied with addressing the need for COVID-19 treatments and vaccines. The product launched last year without the interchangeability designation.

An interchangeable designation means that Semglee can be substituted for Lantus automatically by pharmacists without physicians' permission. All 

 in anticipation of interchangeable biosimilars, however, and these describe conditions under which pharmacists can substitute these agents. Predominantly, patients must be told they're getting a biosimilar substitute for the reference product and some type of registry must be created so physicians can find out that biosimilars have been dispensed. In addition, pharmacists generally will not be allowed to dispense interchangeable biosimilars if the prescribing physicians have expressly indicated on prescription forms that the originator brand is to be used. 

As with other biosimilars approved in the United States, the FDA has added a suffix to the nonproprietary name; in this case Semglee will be referred to as "insulin glargine-yfgn."

Insulin glargine is a long-acting human insulin analog to enhance glycemic control in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.

Biosimilars are approved by the FDA as having highly similar safety and efficacy to the reference brand and "no clinically meaningful differences." Physicians are free to use them not only for the indication they were expressly approved for, but also for extrapolations for which the original brand has been approved. For example, a bevacizumab biosimilar may have been approved for colorectal cancer, but also may be used for nonsquamous non–small cell lung cancer. 

The interchangeable designation is not meant to suggest that interchangeables are superior to biosimilars, but in order to obtain the designation, biosimilar developers generally must perform switching studies that provide evidence that patients who use first the originator or biosimilar and then switch to the other do not experience higher rates of adverse events or decreased efficacy. 

Therefore, the interchangeable designation does create the impression that there may be a difference between a general biosimilar and an interchangeable, and some in the biopharmaceutical industry have speculated that interchangeables will create confusion and possibly discourage use of standard biosimilars. In fact, there is some debate among manufacturers about the value of interchangeable status. 

The company Alvotech of Reykjavik, Iceland, is banking on interchangeable status for its pending adalimumab high concentration biosimilar (AVT02), which would be the first high concentration adalimumab in the United States. The company has submitted "intention to market" notice that it will market the product in November 2021, but Alvotech is currently entangled in litigation with the maker of the originator (Humira) over patents protecting Humira from competition. 

, Biocon Biologics and its distribution partner, Viatris (formerly Mylan), have sought biosimilar and interchangeable status for this product separately because they felt it would improve the product's marketability. Because it is the first interchangeable insulin biosimilar to Lantus, the FDA approval gives Semglee 12 months of product exclusivity before the next interchangeable biosimilar to Lantus can be approved, according to Biocon Biologics. 

"Commercial preparations for launch are underway," the company said in a statement. 

“We are extremely proud to be the first to obtain approval of an interchangeable Biosimilar product in the United States. It is a milestone achievement for both Biocon Biologics and our partner Viatris. This will allow pharmacy level substitution and thereby provide convenient and affordable access to Semglee, a quality biosimilar insulin glargine," said 

Kiran Mazumdar-Shaw, executive chair for Biocon Biologics.

In early 2020, insulins were added to the biologics that are approved under the Biologics Price Competition and Innovation Act approval pathway. There is much debate over whether their approval as biosimilars will help to bring more competition to the insulin market, although that was the intention. Lantus was Sanofi's second best selling pharmaceutical product in 2020 and generated $2.7 billion in worldwide revenue. 

"Biosimilars marketed in the United States typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products," the FDA wrote.

According to the FDA, interchangeables carry the following criteria:

The interchangeable is biosimilar to the reference product,

They produce the same clinical result as the reference product in any given patient.

There is no greater safety or diminished efficacy risk from switching between the interchangeable biosimilar and the reference product.

In tandem with the approval announcement, the FDA made available 3 

fact sheets today for health care providers

 about interchangeables for patients and caregivers.

Semglee is used subcutaneously once daily and is distributed in 10 mL vials and 3 mL prefilled pens.

"This approval furthers FDA’s longstanding commitment to support a competitive marketplace for insulin products. The availability of interchangeable biosimilar insulin products can provide more treatment options to patients, potentially lowering treatment costs and enabling greater access for more patients," the FDA wrote.

After much anticipation, the FDA approves the first interchangeable biosimilar, which is hoped to bring down the high cost of insulin.

FDA Approves Semglee Insulin Glargine as First Interchangeable Biosimilar

 biosimilar revenues up 88% from the comparable second quarter of 2020. These were dwarfed, however, by sales of the Pfizer-BioNTech COVID-19 vaccine. 

Biosimilar sales for the second quarter of 2021 were $559 million globally, primarily fueled by the launches of bevacizumab (Zirabev), rituximab (Ruxience), and trastuzumab (Trazimera) biosimilars.

The company also reported ongoing growth in sales of its epoetin alfa biosimilar (Retacrit) in the United States. Retacrit was launched in 2018 and remains the only epoetin biosimilar in the United States.

Pfizer also reported a 19% decline in global sales of its etanercept originator product (Enbrel) owing to biosimilar competition in Europe and Japan. Enbrel does not yet face biosimilar competition in the United States.

Although growth in biosimilar sales at Pfizer has been robust over the past year, the company’s core business focus is now commercialization of its mRNA COVID-19 vaccine (BNT162b2) and regulatory interaction globally to broaden access and flexibility for use of this product.

Pfizer said it anticipates 2021 revenues of $33.5 billion for BNT162b2, which reflects 2.1 billion doses that Pfizer had contracted to deliver as of mid-July 2021. The company reported overall second quarter 2021 revenues of $19 billion, up 86% from the comparable 2020 quarter.

Without the COVID-19 vaccine, Pfizer’s revenues would have climbed just 10% overall, to $11.1 billion, the company said.

For a report on the company’s first quarter 2021 revenues, click 

Pfizer reported strong sales for its biosimilars portfolio, but these were eclipsed by the massive success of the company's mRNA vaccine for COVID-19.

Small Step for Pfizer's Biosimilars; Leap for Its COVID-19 Vaccine

BioFactura, an Australian company, said it has initiated a phase 1 

 for its ustekinumab biosimilar candidate (BFI-751), referencing Janssen Biotech’s blockbuster product Stelara. Ustekinumab is used for the treatment of Crohn disease, ulcerative colitis, plaque psoriasis, and psoriatic arthritis. The drug works by reducing inflammation in the body.

The single-dose, subcutaneous administration clinical trial will assess the effects of the biologic on healthy volunteers in what will be the first in-human trial of the biosimilar candidate. The comparative study will evaluate the pharmacokinetics of BFI-751 with product samples of Stelara available in the US and EU markets.

Safety and tolerability of BFI-751 also will be assessed, along with immune response. Study sites will be in Brisbane and Adelaide, Australia, and Auckland, New Zealand.

Multiple ustekinumab biosimilar candidates are in development, and in the month of July 2021 alone, several biotechnology companies announced trial progress, including 

. In addition, Dong-A St and Meiji Seika Pharma reported they have agreed on 

 for their own ustekinumab candidate (DMB-3115).

There are no interchangeable biosimilars at the writing of this article, but that could change any minute, given the expectations surrounding the FDA’s 

 of an insulin glargine (Semglee) product. This biologic is approved for use but does not have an interchangeable designation, which would allow pharmacists to substitute this biosimilar for the reference product (Lantus) without physician authorization.

However, the FDA’s determination on this and other biosimilars deemed interchangeable would still be subject to state laws that govern the circumstances under which biosimilars may be used interchangeably.

All states have passed interchangeable laws in anticipation of this class of biosimilars, and to make it easy for health care practitioners and pharmacy professionals to understand which rules apply, Cardinal Health, a health care services and products company, has created an 

 that allows users to look up interchangeability standards by state.

What is typical of these laws is that physicians must be provided notice of a biosimilar substitution after it happens, and substitutions cannot be made if the physician has expressly indicated on the prescription that the originator product is to be used. These state laws often specify that patients must be notified if they have been given a biosimilar instead of an originator product. The state-by-state laws are spelled out 

BioFactura looks to join the ustekinumab biosimilar race and Cardinal Health provides an interactive tool with state-by-state interchangeable rules.

BioFactura Initiates Ustekinumab Trial and Cardinal Health Launches Interactive Map for Interchangeables 

Many new treatments for cancer are helping to alleviate the burden for patients, but at the same time, the cost of care is increasingly recognized as a “toxicity” of treatment. With high out-of-pocket expense, “it becomes hard for patients to sustain an appropriate level of cancer care,” said Kashyap B. Patel, MD, a medical oncologist and Advisory Board member for The Center for Biosimilars®.

For example, when patients retire from work, they often do not have Medicare supplemental insurance—Medigap—to help with the cost of co-pays, coinsurance, and deductibles, he noted in a recent Axios-sponsored webinar discussion about biosimilars and the costs of cancer care. Patel is also CEO of Carolina Blood and Cancer Care Associates in Rock Hill, South Carolina.

Among Medicare beneficiaries, as many as 19% do not have secondary insurance, he said. “Their out-of-pocket costs could vary between $2500 to $15,000, which is almost as much as what some of them make in some regions, so the benefits of cancer care are not reaching the populations we need to serve most.”

Among patients who have commercial coverage, the coinsurance payment, which is what patients pay after they’ve met their deductible, may range from 6% to 20% of costs, depending on the plan, according to Patel. “The system is not designed to look after the ultimate beneficiary, which is the patient.”

That said, Patel’s cancer treatment center is among 126 practices nationwide that are participating in the Oncology Care Model, which is a CMS pilot program to reduce costs of cancer care while increasing the value and quality of treatment afforded to patients. More emphasis needs to be placed on reducing out-of-pocket cost so that patients can get the full benefit of available therapies without suffering financial toxicity, Patel said.

In the health care community, he said, that message may not have filtered in. 

“I’m not saying that my colleagues are not really conscientious, but they have not been appropriately educated about the potential benefits of reducing the out-of-pocket costs, as well as total cost of care,” he said.

More thorough attempts to educate health care providers about biosimilars and the use of incentives to promote employment of these agents can achieve this aim, Patel said. Such incentives were described in a separate portion of the Axios discussion that featured Rep Kurt Schrader, D-Oregon, who discussed a bill that would 

Patel said that in his oncology practice biosimilars help him to save 35% on the cost of biologics, and for the population of Medicare beneficiaries he serves who do not have supplemental insurance, that savings could trim as much as $10,000 off their out-of-pocket costs of care.

Kashyap B. Patel, MD, says value of care is an important metric, but often people lose sight of what patients have to pay out of pocket, and how this affects them. 

Oncology MD: Out-of-Pocket Expense Deserves More Attention

Rep Kurt Schrader, D-Oregon, is hoping for a stronger embrace in the health care community of his bill to increase reimbursements for use of biosimilar agents. And more public enthusiam could persuade the FDA to approve more of these cost-saving biologics, he said. 

Biosimilars are generally lower-cost agents that can be used in place of costly originator biologic brands, and Schrader and Rep Adam Kinzinger, R-Illinois, have introduced a bill for creation of an act called Bolstering Innovative Options to Save Immediately on Medicines Act (

), which would stimulate the use of biosimilars by increasing the add-on incentive payment to physicians who prescribe them.

“I’m not entirely sure that we’re going to solve this with the incentive payment, but sometimes, as we all know, in real life you have to spend a little money to save a little money,” Schrader said in a recent webinar sponsored by Axios.

Biologics are a rapidly growing budget item in health care, and biosimilars of originator biologics hold the potential for reducing this cost. For example, a 

 from the Congressional Budget Office noted that 30% of net Medicare Part D and Medicaid prescription drug spending in 2015 was for specialty drugs, which include biologics, but this spending amounted to just 1% of total prescriptions for both government programs.

Currently, providers are reimbursed the average sales price (ASP) of the biosimilar and, in addition, receive 6% of the ASP of the originator brand that the biosimilar is based on. This is thought to ensure that it isn’t more profitable for them to prescribe the originator product rather than the biosimilar.

Schrader and Kinzinger’s bill is predicated on the assumption that raising the originator drug percentage add-on to 8% would serve as a greater incentive for use of biosimilars. Physicians sometimes contend that they do not receive the full add-on percentage and what they do receive does not cover their full costs of treatment.

Biosimilar ASPs are declining at the rate of 

, which is a sign that competition from these products is resulting in savings for the health care system, but savings vary across the 7 types of biologics for which biosimilars are available in the United States, according to a recent Amgen report.

And costs of originator brands, despite biosimilar competition, often move downward only stubbornly. For example, since the inception of biosimilars for trastuzumab (Herceptin), the originator ASP has declined 5% or less by the end of the first quarter of 2021. By contrast, biosimilar discounts for trastuzumab had reached 30% or greater.

In his remarks, Schrader attributed such behavior to physician preference for prescribing well-established brands. “I’ll tell you that as a veterinarian in my previous career, I got comfortable with certain brand-name drugs that were the first to come to the marketplace. You don’t want to change what’s working for you. It takes a little push sometimes to get off using the medication or pharmaceutical agent you’ve used again and again, to get patients and your clients to try a different medication that might be the exact equivalent.”

Schrader described biosimilar uptake in the United States as disappointing compared with results in the European Union. He said a good public relations campaign could promote these agents and improve the savings. “It’s a paltry amount in the United States.”

The FDA right now is a little understaffed. It has lots of obligations, and I think they’re doing a little triage within their own office as to which [projects] they’re going to put their manpower behind. 

He also noted that there have not been many biosimilar approvals by the FDA lately, which he said is contributing to the problem. In 2019, 10 biosimilars were approved, and in 2020 just 3 were approved. So far in 2021, none have been approved.

The reason for this falloff is that the FDA has been distracted by other concerns, but a PR campaign could help to persuade the FDA to divert more resources toward the review and approval of biosimilar applications, he said.

“As you start to get the pickup, then I think the FDA will start to prioritize even more [biosimilars] for availability in the marketplace. The FDA right now is a little understaffed. It has lots of obligations, and I think they’re doing a little triage within their own office as to which [projects] they’re going to put their manpower behind. I think that once we start getting some increased biosimilar uptake, we can then encourage the FDA to continue to approve more and more of these biosimilars,” Schrader said.

Biosimilar uptake could be more robust in the United States if the FDA can be convinced that biosimilars are worth the effort, according to Rep Kurt Schrader, D-Oregon.

Congressman Schrader Describes Frustration With Biosimilar Uptake 

Using data from a study (N = 220) of the infliximab biosimilar CT-P13 in patients with Crohn disease, investigators said they have improved understanding of the clearance of infliximab and its predictive value for the development of antidrug antibodies (ADA).

Investigators found that initial infliximab clearance, concomitant use of immunomodulators, and infliximab dosage were statistically significant predictors of the time to development of ADAs.

Investigators reported that the risk for ADA increases 61% for every increase of 0.1 L/day in drug clearance; however, it decreases by 41% if immunomodulators are administered concomitantly, and it also decreases 29% with every increase in dosage of 100 mg.

They calculated that for a patient with infliximab clearance of 0.2 L/day who is not taking immunomodulators and has an infliximab dose of 328 mg, the average time to first ADA would be 374 days.

With higher clearance of 0.4 L/day, also with dosage of 328 mg and no immunomodulators, the ADA onset would occur in 144.5 days.

A higher starting infliximab dose of 428 mg would lengthen the time to onset to 203 days, and adding immunomodulator treatment would extend time to ADA onset to 354 days, they said.

“Our results suggest that early assessment of clearance should guide treatment optimization with infliximab in patients with Crohn disease, including the addition of concomitant immunosuppressants or increasing the dose during induction,” authors of the study concluded.

Kutschera M, Primas C, Reinish S, et al. Initial clearance of infliximab is a predictor for the time of formation of anti-drug antibodies. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster DOP74

Concomitant use of immunomodulators and dosage are important variables in the development of antidrug antibodies (ADAs) for patients receiving infliximab for Crohn disease, investigators report. 