Christine Simmon is the executive director of the Biosimilars Council and senior vice president of policy and strategic alliances at the Association for Accessible Medicines (AAM). Christine leads policy development and issues management for AAM and has led the Biosimilars Council since its founding in 2015.

Christine Simmon

As the biosimilar market continues to expand, many health systems and insurance companies will start making the decision on what product—the innovator or the biosimilar&mdash;will be on their formulary. Health systems will have a difficult time making this decision, which will be driven by their medical staff’s acceptance of biosimilars, the patient mix, and the predominant insurance provider. Making the decision to use or not to use a biosimilar is much more complex than converting to a generic product or switching agents within a therapeutic class.  

The ultimate formulary decision requires the evaluation of multiple factors as listed below: 

 If physicians do not accept the biosimilar’s qualifications as a product of equal safety and efficacy as the originator biologic, formulary management will be very difficult, and there is the potential for errors with having to carry multiple products.  

Not all pharmaceutical wholesalers will supply the product. Most pharmacy departments purchase products from the wholesaler at a cost minus. If the biosimilar does not come through the wholesaler, the pharmacy is charged a higher price.  

—eligible, providing a competitive 340B price is critical to the formulary decision.   

 For hospitalized patients (inpatients), drugs are reimbursed as part of a diagnosis-related group (commonly known as DRG); so the best-priced product is the preferred product. However, on the outpatient side, the price of the product is as important as the reimbursement. It is important to monitor the reimbursement of outpatient biosimilars to evaluate the overall reimbursement, as the average sales price (ASP) erodes over time. Biosimilars are to be reimbursed at 100% of the ASP for the biosimilar, plus 6% of the ASP for the originator biologic.

 Often, the products are bundled with other products within the company’s portfolio. The overall impact to any existing contracts or rebates need to be calculated.  

 This is an important consideration when determining product storage and dispensing. Changing from a vial to a syringe may require purchasing larger refrigerators for storage. 

 The resources necessary to build the medication record and convert patients will need to be calculated. In addition, new insurance authorizations will be required since the products have different J-codes.

Given that the United States is considerably new in the biosimilar market, the exact degree to which prices will drop remains unknown. The ability to control biologic drug expenditures is challenging because of the complexities of the pharmaceutical supply chain and reimbursement. Overall, one of the most difficult things related to biosimilars will be the ability to accurately predict their value to your health system. It is critical that pharmacists and other stakeholders in the formulary decision process understand the complexity of calculating the overall impact of biosimilars.   

Formulary Management an Important Consideration for Biosimilar Stakeholders

Molly Billstein Leber, PharmD, BCPS, FASHP

Amanda DeMarzo, PharmD, MBA, PACS, is associate director of Patient Access with the National Board of Prior Authorization Specialists, an affiliate of the Accreditation Council for Medical Affairs, based in Oradell, New Jersey. Amanda focuses on how to improve the current health care system as a whole through improved training, widespread certification, and advanced technology for better patient outcomes. She developed a passion for patient-centered care and shared decision-making during patient-facing roles over the last 8 years.

Amanda DeMarzo

In its newly released earnings report for Q4 and fiscal year 2021, Coherus announced Udenyca—one of 4 pegfilgrastim biosimilars on the US market—delivered net sales of $73 million and $327 million, respectively.

But totals were down from those reported in 2020, with Udenyca earning a net $110.4 million in Q4 of 2020 and $475.8 million throughout the year. Decreases were mainly due to a reduction in the number of units sold and a decline in net realized price resulting from increased competition and COVID-19 impacts, the company said in a 

Udenyca is a colony stimulating factor that promotes white blood cell growth and is used to treat neutropenia resulting from cancer medications.

Coherus reported net losses for 2021 Q4 of $45.7 million, or $0.60 per share on a diluted basis compared with totals recorded in the same period in 2020; net losses were also recorded for 2021 as a whole ($287.1 million, or $3.81 per share on a diluted basis, compared with net income of $132.2 million, or $1.62 per share, on a diluted basis for 2020).

From 2020 to 2021, research and development (R&D) costs increased from $142.8 million to $363.1 million, due in large part to an upfront license fee paid to Junshi Biosciences. Costs incurred from the development of Yusimry, toripalimab and additional presentations of Udenyca also contributed to the $220.3 million rise.

Selling, general, and administrative (SG&A) costs increased year over year from $139.2 million in 2020 to $169.7 million in 2021.

In 2022, Coherus expects to launch 2 new products and initiate a clinical trial evaluating toripalimab in combination with JS006, company CEO Denny Lanfear said.

“Looking ahead to 2023, we project accelerating revenue growth with the planned launch of FDA-approved Yusimry into the $17 billion Humira market and the introduction of the Udenyca on-body injector, if approved, a new presentation that would enable us to address the remaining $1.2 billion Neulasta Onpro segment of the pegfilgrastim market where there is currently no biosimilar competition,” Lanfear added.

The company also projects combined R&D and SG&A expenses in 2022 will be in the range of $415 million to $450 million as a result of the anticipated new product launches and the additional presentation of Udenyca.

In its report, Coherus touted the FDA approval of 

 (adalimumab-aqvh), a Humira biosimilar in December 2021 and a biologics license application (BLA) for Cimerli (ranibizumab-ranq), a Lucentis biosimilar which has an assigned a target action date of August 2022.

An April 2022 target action date has been set for toripalimab’s BLA for the treatment of metastatic or recurrent nasopharyngeal carcinoma. It is currently under priority review by the FDA for this indication and is being studied for treatment of lung, breast, liver, skin, kidney, stomach, esophagus, and bladder cancers.

Coherus released its earnings report for the last quarter of 2021 and for the year as a whole. 

Coherus Banks on 2022 Approvals After Net Losses for Q4, 2021

Gianna Melillo

What are your thoughts on the recent launch of Renflexis in the United States?

I think that it will be very interesting to see what happens now that we have 3 versions of infliximab on the market. Will this drive the cost down? I think that it remains to be seen. I think, as you look at what has happened since the first biosimilar for infliximab has hit the market, you have seen insurance companies—United, for example, actually signed a contract with Remicade to stay with the bio-originator. I think you are going to see some of this, but I think it will be interesting to see the uptake and how this happens, and I think we will start to see the outcomes of this moving forward.

Marcus H. Snow, MD, Assistant Professor Rheumatology, University of Nebraska, discusses the recent launch of a new biosimilar infliximab, Renflexis, in the United States. 

Dr Marcus H. Snow: The US Launch of Renflexis

Marcus H. Snow, MD

Sandoz said Tuesday the the FDA approved its citrate-free, high-concentration formulation (HCF) of its adalimumab biosimilar, Hyrimoz.

The adalimumab-adaz injection (100 mg/mL) is approved to treat 7 indications covered by the reference product, Humira, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn disease, ulcerative colitis, and plaque psoriasis.

“As one of the first adalimumab high-concentration formulation biosimilars approved in the US, Hyrimoz HCF has the potential to expand access for millions of people who face the realities of living with a serious inflammatory disease and to enhance the patient experience,” Keren Haruvi, president, Sandoz Inc., head of North America, 

Sandoz set a launch date of July 1 for both versions of Hyrimoz.

The FDA approval was based on a phase 1 pharmacokinetics (PK) bridging study comparing the FDA-approved adalimumab 50 mg/mL to the citrate-free, HCF 100 mg/mL. This study met all of the primary objectives, demonstrating comparable PK and showing similar safety and immunogenicity of the low-concentration adalimumab and the HCF adalimumab.

The original, low-concentration version of Hyrimoz was approved by the FDA in 2018. Another HCF version, Hadlima, from Organon and Samsung Bioepis, was approved in August 2022. Biologics license applications for Alvotech and Celltrion Healthcare's high-concentration adalimumab biosimilars are currently under review with the FDA.

In 2023, up to 10 adalimumab biosimilars will enter the market. The first, Amgen’s Amjevita, launched at the 

; as with Hyrimoz, the others are scheduled to launch starting in July 2023.

Both the high-concentration and low-concentration versions of adalimumab-adaz (Hyrimoz) injection will launch in July, along with a wave of other biosimilars to Humira (reference adalimumab).


FDA Approves Sandoz’ High-Concentration Version of Adalimumab Biosimilar, Hyrimoz

Allison Inserro

Celltrion presented data at the American College of Rheumatology (ACR) meeting on November 14, demonstrating that its product CT-P10 is as safe and effective as Rituxan for the treatment of rheumatoid arthritis (RA).

, investigators tested CT-P10 against both US- and EU-licensed versions of rituximab. The study evaluated pharmacokinetic and pharmacodynamics, as well as safety.

Three hundred seventy-two patients participated in the study. A total of 161 were given CT-P10 and the remainder were given the originator product.

The investigators concluded that the pharmacokinetics of CT-P10 were highly similar to those for the originator products (90% confidence intervals were within the equivalence range of 80% to 125%), and the safety profile was noninferior. Infusion-related reactions occurred in 6 (9.4%) of patients in the biosimilar group, 4 (6.2%) in the US-licensed version of rituximab, and 12 (20%) in the EU-licensed group, and all of these reactions were either grade 1 or 2. Discontinuations as a result of an adverse event occurred in 3.1%, 4.6%, and 1.7% of patients taking the biosimilar, US version, and EU version, respectively.

 at the American College of Rheumatology meeting,  a team of researchers sought to gather efficacy data on the biosimilar versus the two licensed versions of Rituxan, using the DAS28-CRP/ESR as a primary endpoint.They found in this phase 3, controlled study, that the biosimilar was therapeutically equivalent to the other treatment groups, with a change in DAS28-CRP of -2.14 for the biosimilar vs. -2.09 for the originator products. Additionally, the change in DAS28-ESR scores were -2.41 vs. -2.35, respectively. ACR 20, 50, and 70 scores were equivalent as well. No significant differences in adverse events were detected among the groups, and no serious complications were reported.

Biosimilar rituximab is being tested not only in patients with RA but in those with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), and polyangiitis. If it is approved for treatment, Celltrion’s product would likely be the first CD20-inhibiting monoclonal antibody to reach the market in a biosimilar version.

Celltrion announced that on November 17, 

 for use in South Korea for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. It will be marketed under the name Truxima in that country.

Pharmacokinetics of CT-P10 were highly similar to originator products. 

Ritumixab Biosimilar Demonstrates Positive Results in Rheumatoid Arthritis

Stanton R. Mehr

All eyes in the world of biologics and biosimilars are on the Supreme Court as it decides a constitutional challenge to the Affordable Care Act (ACA) in 

 provisions of the ACA, at stake is the future of the Biologics Price Competition and Innovation Act (BPCIA), which was signed into law on March 23, 2010 as Title VII to the ACA and provides a pathway to market for biosimilar products. For biologic and biosimilar stakeholders, the focus is on whether the Supreme Court will let the BPCIA stand even if it finds provisions of the ACA to be unconstitutional.

The Constitutional Challenge: Can Congress Require a Tax of Zero Dollars?

The ACA was intended to lower insurance premiums and overall health care costs by broadening the insurance pool with the individual mandate, which required individuals to maintain insurance coverage or pay the Internal Revenue Service a “shared responsibility payment.”

National Federation of Independent Business 

, the Supreme Court in 2012 upheld the ACA’s individual mandate under the taxing power of Congress. But in 2017, Congress amended the ACA to set the shared responsibility payment to $0. A number of states and private citizens sued. They argued that the now nonexistent shared responsibility payment cannot be a constitutional exercise of Congress’s power to tax. But that is not the end of the line for the BPCIA. If the individual mandate is unconstitutional, the Supreme Court will have to decide whether it can be “severed” from the rest of the ACA, allowing other provisions of the ACA, including the BPCIA, to remain in place.

Severability, a doctrine that goes back at least to Chief Justice John Marshal in the early 1800s, allows a court to save statutes with unconstitutional provisions by cutting out the invalid part of the law. The basic question is whether Congress would have intended the entire statute to remain without the unconstitutional provision. During Justice Amy Coney Barrett’s recent confirmation hearing, she explained that severability is like a game of judicial Jenga. Once a court identifies an unconstitutional provision, the court must pull out that unconstitutional block. But if the statutory “tower” cannot stand without that block, then the court cannot use severability to save the remainder of the statute.

Many conservative justices have questioned how the severability doctrine can be applied to the ACA. The late Justice Scalia is one example. In a dissent in the NFIB case, he stated that the ACA was not severable, comparing the ACA to a Christmas tree with each member of Congress adding ornaments, making it impossible to discern what should remain if the tree were taken away.

Oral Argument: Playing “Gotcha” With the BPCIA?

There was almost no mention of the BPCIA during the Supreme Court’s oral argument Tuesday in 

. Counsel for the state of California did raise, however, the biosimilar provision in passing as one provision in the statute on which the public relies. Although not the focus of the argument, that reference will not go unnoticed, especially in light of an amicus brief focused directly on the severability of the BPCIA filed by the Association for Accessible Medicines.

Justice Barrett did not show her cards during oral argument. She had, however, stated during her confirmation hearing that she held in a moot (simulated) court competition for law students that the individual mandate could be severed from the ACA. Although a moot court judge’s hypothetical ruling in an academic exercise is not a good basis to predict how she will rule in the actual case, 2 of the conservative-leaning justices made strong statements Tuesday about severability during oral argument.

Chief Justice John Roberts asked whether Congress would “want the rest of the law to survive if the unconstitutional provision were severed.” The chief justice said that there was “compelling evidence on the question,” namely that in 2017 when Congress set the shared responsibility payment to $0, “Congress left the rest of the law intact.”

Justice Brett Kavanaugh also seemed inclined to sever the individual mandate. In an earlier case, he, wrote “Constitutional litigation is not a game of gotcha against Congress, where litigants can ride a discrete constitutional flaw in a statute to take down the whole, otherwise constitutional statute.”

 During the argument by counsel for the House of Representatives, who echoed that thinking, Justice Kavanaugh stated that the severability question was “very straightforward under [Supreme Court] precedents, meaning that we would excise the mandate and leave the rest…in place.”

If Chief Justice Roberts and Justice Kavanaugh side with Justices Stephen Breyer, Sonia Sotomayor, and Elena Kagan, who are widely expected to vote for severability if the court says that the ACA is unconstitutional, then the BPCIA could survive this latest challenge to the ACA. After oral argument, the initial consensus has been that severability is likely if the court holds the individual mandate of the ACA unconstitutional. But as veteran court watchers know, it is not unheard of for the justices to make statements in favor of a position only to vote against it later. Biosimilar manufacturers should continue to advance contingency plans for a post-BPCIA world, just in case the Supreme Court yells “Jenga!”

1. Barr v Am. Ass’n of Political Consultants, Inc

Intellectual property attorneys discuss the Supreme Court oral arguments over the Affordable Care Act (ACA) and implications for the Biologics Price Competition and Innovation Act (BPCIA).

Legal Opinion: BPCIA Is Likely to Survive Latest ACA Challenge

Chad Landmon is a partner at Axinn, Veltrop & Harkrider LLP, where he chairs the firm’s Intellectual Property and FDA Practice Groups. He focuses his practice on patent litigation and counseling and food and drug law, with an emphasis on pharmaceuticals, biologics, medical devices, regenerative medicine, and human tissue products.

Chad Landmon, JD

In the 10 years since the passing of the Biologics Price Competition and Innovation Act (BPCIA), the field of biosimilar legislation and litigation has rapidly expanded, creating a new, complex legal environment. To help navigate the expanding biosimilar legal space, Goodwin law released the 

Guide to Biosimilars Litigation and Regulation in the U.S.

 which provides a guide to each section of the BPA. Goodwin partners Robert Cerwinski, JD, and Alexandra Valenti, JD, discussed the guide on a recent 

“The guide covers all legal and regulatory issues that we've either already seen litigated or expect to see litigated in the coming years that relate to biosimilar products,” Valenti said. The publication is meant as both a guide for those who work closely with biosimilars and biosimilar litigation as well as for those who are new to the space. 

Valenti noted that since the passage of the BPCIA, the Supreme Court, in 

, resolved the issue as to whether a private party had the ability to enforce the act's provisions that pertain to the prelitigation information exchange, or patent dance. "That decision also held that notice of commercial marketing under the statute could be given at any time by the biosimilar, that the biosimilar didn't need to wait for product approval to provide notice of commercial marketing," she said.

One possible issue that is being watched is to see if product liability claims arise in biosimilars. “The interesting thing that we’ll be watching in that space is whether federal preemption principles that have been held to shield generic small molecule drug manufacturers from certain types of product liability claims will also apply in the biosimilar context,” Valenti said.

Anotjher issue to watch is the streamlining of patent issues by district judges, said Cerwinski. A judge may attempt to manage the process in such a way that might be considered more timely and efficient, but this is raising concerns by branded manufacturers.

“Brands have really been concerned about this as a streamlining by district court judges on the ground that not permitting a brand or a patentee to assert whatever patents the [Patent Trade Office] PTO has issued it is unconstitutional,” Cerwinski said. “And is somehow taking a property right or preventing them from exercising them property right? And we expect to see that actually appealed all the way up to the Supreme Court at some point.”

To learn more about the Guide to Biosimilars Litigation and Regulation in the US, visit the purchase page 

What is ahead for biosimilar litigation? We highlight a recent interview Goodwin partners gave recently about their new guide to biosimilar litigation. 

What's Ahead for Biosimilar Litigation?

Sara Karlovitch

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

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

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

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

Repurposed contracting and promotional activities: 

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

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

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

Delays in biosimilar approvals and clinical trials: 

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

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

Increased budget pressure can accelerate postcrisis biosimilar usage: 

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

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

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

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

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

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

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

Authors