Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Janet Woodcock, MD, acting commissioner of the FDA, delivered an upbeat report on biosimilars and generics progress as keynote speaker of the Association for Accessible Medicines’ GRx+Biosims annual conference this week.

She addressed the HHS recommendations for pricing reforms in the drug industry, noting that many patients are not adhering to their medications because of high prices, and also said that, now that COVID-19 pandemic is more under control, the FDA is returning to business as usual, addressing applications for biosimilar and generic approvals and conducting domestic factory inspections, at least, in a normal fashion.

“Now, I am pleased to say that as of July we began resuming normal operations for domestic inspections,” Woodcock said.

“While our agency does not play a direct role in drug pricing, we can, by encouraging development of lower-cost generic and biosimilar products, support competition in the health care market,” she said.

“The savings impact to Americans as a result of the lower costs of these generic and biosimilar products is enormous. In fact, last year, Americans saved $338 billion by using generics and biosimilars, and that’s an increase of $18 million from 2019,” she said.

“In the biosimilar space, new launches and improved utilization led biosimilar savings last year to grow more than 3 times the $2.5 billion saved in 2019, with an especially high impact in oncology,” she said.

Woodcock reported success at the FDA in adjusting user fees for generic and biosimilar application reviews. The user fees help to ensure that the FDA has sufficient funds for conducting these reviews for approval.

She said the FDA is working closely with industry on ways to “maximize scientific and regulatory clarity and ways to enhance efficiency in the review process. We are nearing the completion of that process, as well.”

The agency is sometimes criticized for requiring forms of evidence for drug approval that appear redundant or outdated in the face of modern methods for analyzing and determining safety and efficacy of agents. Use of outdated methods can add significantly to the cost of bringing drugs to market.

The COVID-19 pandemic has represented serious obstacles to the smooth functioning of the FDA because of the drain on its resources; however, Woodcock said “We’ve maintained FDA standards in evaluating products based on high quality data and sound science, and largely continued to meet our…commitments for reviewing applications in a timely manner.”

The agency has approved or tentatively approved hundreds of abbreviated new drug applications in fiscal 2021 alone, and this year the FDA achieved 2 firsts when it approved the first interchangeable biosimilar monoclonal antibody and the first 

“We have now approved 31 biosimilars for 11 different reference products, and the future looks even brighter with interest continuing to grow. As of October 1, 2021, 94 biosimilar development programs were underway, and the FDA has received meeting requests from companies for the development of biosimilars for 46 different reference products,” Woodcock said.

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Janet Woodcock, MD, acting commissioner of the FDA, said the agency is meeting with biosimilar developers for biosimilars for 46 reference products.

FDA’s Woodcock Says Agency Has Resumed Normal Review Pace for Biosimilars, Generics

Amjevita, the adalimumab biosimilar, figures prominently in Amgen’s plans for growth, such that the company made it a prominent feature of its earnings discussion for third quarter 2021 results.

Sales of the product rose 39% compared with the comparable year-ago quarter, although volume growth was up 73%. The difference was attributable to lower net selling price, as competition among adalimumab products drove down prices, company officials explained. The company boasted that Amjevita is the best-selling adalimumab biosimilar in the European Union.

“We expect to bring Amjevita, our biosimilar to Humira (reference, AbbVie) to the United States in 2023. We expect to replicate the success we've had with Amjevita in many other markets around the world,” said Robert A. Bradway, chairman, CEO, and president of Amgen. The company said it has a trial under way to help qualify Amjevita for interchangeable status, which would allow pharmacists to substitute the product for reference brands.

The product brought in $111 million in revenues in the quarter just ended, up from $80 million a year earlier.

Biosimilars contributed to 4% overall revenue growth at Amgen in the third quarter, for $6.7 billion in total revenue across all product categories. Mvasi, a bevacizumab biosimilar, was named as one of the key drivers of that growth.

Mvasi brought in $187 million in revenues in the United States and a total of $274 million worldwide, up 19% from $231 million in the comparable year-ago quarter. The company said volume of sales was up 54%, although net prices were lower.

“In the United States, Mvasi continues to hold leading volume share with 49% of the bevacizumab segment in the quarter. We expect that continued worldwide volume growth from Mvasi will be offset by declines in net selling price due to increased competition,” Amgen said.

Sales revenues for the company’s trastuzumab biosimilar Kanjinti declined 31% this quarter vs the comparable year-ago quarter. Lower net selling prices were the cause, as volume of unit sales increases 18%. “In the United States, Kanjinti continues to hold leading volume share with 41% of the trastuzumab segment in the quarter. We expect net selling price to continue to decline as a result of increased competition.”

Amgen reported net income of $1.9 billion for the quarter just ended, down from $2.0 billion a year ago. The company attributed the decline to expenses related to a licensing deal with Kyowa Kirin.

The company said it is breaking new ground in the development of inflammation treatment products, explaining it expects to report phase 3 data soon for biosimilar candidates for ustekinumab (Stelara), for plaque psoriasis and psoriatic arthritis; aflibercept (Eylea), for macular degeneration; and eculizumab (Soliris), for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Amgen said sales of Enbrel (etanercept), which faces biosimilar competition abroad but not yet in the United States, declined 3% compared with the year-ago quarter, driven by a 2% decline in volume of units sold. The company said the decline in volume has been slowing in recent quarters.

Total sales of a basket of established Amgen agents, which include the pegfilgrastim (Neulasta), filgrastim (Neupogen), and epoetin alfa (Epogen), originator products, each of which faces heavy biosimilar competition, declined 21% on average, “primarily driven by volume declines and lower net selling price. Going forward, we expect increased competition to result in additional net price and volume erosion across this portfolio of products,” the company said.

Broken down by agent, Neulasta revenues declined to $415 million from $555 in the comparable 2020 third quarter (–25%); Neupogen, $52 million vs $65 million (–20%); and Epogen, $138 million vs $149 million (–7%)

Amgen reported the following progress for biosimilar candidates:

A phase 3 study of ABP 938, referencing the aflibercept product Eylea. The study is enrolling patients and data are anticipated in 2022.

Phase 3 studies of ABP 654, referencing Stelara, and ABP 959, referencing the eculizumab product Soliris. Data are anticipated in 2022.

Phase 3 studies to support an interchangeability designation in the United States for ABP 654 and Amjevita are enrolling patients.

Most recently Pfizer announced that it was seeking to obtain 

status for Abrilada, also an adalimumab product, set to launch in 2023.

In its third quarter earnings report, Amgen addressed the give and take of biosimilar competition.

Amgen Discusses Interchangeable Status for Its Adalimumab Biosimilar

As the House moved toward a vote on the $1.75 trillion Build Back Better Act (BBBA), the Association for Accessible Medicines (AAM) stepped up efforts to block elements of the bill that would enable Medicare to institute caps on drug prices, negotiate drug prices, and force manufacturers to pay “rebate penalties” if their drug price increases exceed the general rate of inflation.

“This is jarring what this proposal could do to the generics and biosimilars industry, but more importantly, what it can do to seniors who rely on affordable medicines,” Dan Leonard, MA, president and CEO of AAM, said in a press conference. AAM is a trade association of biosimilar and generics manufacturers.

The group contends that generics and biosimilars are the good guys in the effort to rein in drug price inflation and said the price-reducing effect of these agents could be “dampened” by policies under consideration in Congress. Further, the proposed policies threaten to undermine the sustainability of generics and biosimilars manufacturing, they said.

“Generics and biosimilars today account for 90% of the prescriptions filled in this country, but only 18% of the total spend on drugs, so 10% of the drugs are driving 82% of the spend,” Leonard said.

Under the BBBA, which remains a work in progress, with last-minute revisions, the prohibition on Medicare for negotiating drug prices under Medicare Part D would be ended. Drug price negotiations also would be extended to Part B and would affect originator brands for which there is no competition. 

Biosimilars are covered under both Part D and Part B and although they apparently would not be affected by any negotiation requirement, the AAM's 

does include manufacturers of originator, or reference, brands and the biosimilars and generics that compete against them. The AAM's opposition to drug price negotiations serves the interest of these originator companies. 

Also under the BBBA, Medicare would gain the ability to limit negotiated prices to 120% of the Average International Market price as determined by prices in markets abroad (Australia, Canada, France, Germany, Japan, and the United Kingdom).

An additional BBBA provision would require manufacturers to reimburse or “rebate” Medicare Part B and Part D if their drugs exceed the rate of urban Consumer Price Index (CPI-U) inflation. The rebate would equal the total drug cost minus the average sales price with the CPI-U inflation value included.

CMS has estimated that drug price negotiations would lower cost sharing for Part D enrollees by $102.6 billion between 2020 to 2029 and Part D premiums for Medicare beneficiaries by $14.3 billion. The BBBA would extend the negotiated price options to private health insurers, and CMS has estimated savings of $54 billion between 2020 and 2029 for their patients.

Christine Simmon, JD, AAM’s executive vice president of policy and strategic alliances, said the timing of the policy initiatives would injure the nascent market in biosimilars. With 31 approved and 21 launched, “the biosimilar market is certainly in its early days, but it is proving its vitality and it’s delivering the savings for patients,” she said.

Biosimilars require an investment of $100 million to $300 million to develop, and FDA approval can be a 10-year process, she said. “If you add on top of that the time it takes to challenge patents and the significant litigation costs, we’re talking about a significant investment.”

Wayne Winegarden, PhD, director of the Center for Medical Economics and Innovation at Pacific Research Institute, a conservative think tank, commented that the proposed rebate penalty would interfere with the smooth operation and efficiency of the free market.

“The CPI provision is a form of price control, and price controls inevitably lead to adverse consequences. In the case of generics, there is no reason to believe that changes in the costs of production for any given year will reflect the average change in prices reflected in the CPI,” he said.

“The pricing limitation consequently creates a new risk for manufacturers—specifically, that a price spike in the costs of materials or production will turn a profitable product into an unprofitable one,” he said.

Some institutions that have done analysis of the rebate provision have speculated that manufacturers might start charging higher prices when their drugs enter market to pad against the inflation penalty. Winegarden agreed with that, and added, “Alternatively, these higher risks could discourage the production of several types of generic medicines altogether.”

The BBBA provisions were spurred in part by contentions that drug manufacturers abuse their product exclusivity (patents) by raising prices far more often than necessary and often in advance of the arrival of competing products, to add last-minute profits to their revenue total.

 often cited is AbbVie’s pricing program for the adalimumab product Humira, for which the cost of an annual course of treatment climbed from $13,589 in 2003 to $77,586 in 2021, on the back of 27 separate price increases, sometimes multiple increases in a single year.

Asked why the AAM membership would not be satisfied with CPI-adjusted price increases, Leonard said that generics often sell for so little that prices would need to be raised higher than a CPI increase. “If you have a generic priced at $1 a unit, and it goes up a couple cents, that triggers the penalty. And because of the low margin that our members operate under, that threatens the ability to sustainably produce that medicine and increases the risk of shortages,” he said.

Simmon said the Humira pricing example underscores the value of biosimilars and the importance of preserving the existing framework for determining price.

In 2023 at least 6 FDA-approved biosimilar forms of adalimumab will enter the marketplace, she noted. “We’re all looking very much forward to 2023, when we can have competition for a key biologic product and provide that access and savings for patients.”

As House leaders sought to build support for the Build Back Better Act, the Association for Accessible Medicines (AAM) objected to drug price negotiations and proposed “rebate penalties.”

AAM Jousts With Rebate Penalties for Generics and Biosimilars

Prime Therapeutics, a large pharmacy benefit manager (PBM) with 33 million Blue Cross and Blue Shield plan members, said it will put the insulin glargine biosimilar Semglee on its preferred formulary.

Semglee was approved as an interchangeable biosimilar by the FDA in July 2021, and Prime’s decision to promote use of this agent follows a similar decision in October by Express Scripts, another PBM, which put the agent on its largest national formulary.

in August 2020 by Biocon Biologics and Mylan (now Viatris) but did not obtain biosimilar and interchangeable status until July 2021. 

means the drug can be switched for the reference product (Lantus) at the discretion of the pharmacist.

"This formulary change reinforces Prime's commitment to increasing biosimilar adoption and also demonstrates that we are not beholden to rebates, as we're able to also prefer the lowest net cost therapy," Kelly Pokuta, vice president and chief trade relations officer for Prime, said in a statement.

Rebates and discounts offered by manufacturers often cloud the pricing picture for biosimilars and reference products, so it’s often unclear to the public which is the lower-priced agent and how much the agent is actually selling for.

The PBM vowed in its statement that there would be “no significant member disruption and affordability will be comparable or better with the biosimilar.” The formulary placement would take effect on January 1, 2022.

Semglee is the only insulin glargine product that is available in biosimilar or interchangeable form currently in the United States.

There is a pipeline of insulin products that are expected to debut as biosimilars in the near future, posing competition for dominant reference brands, which have maintained often stubbornly high and increasing prices to the detriment of affordability and access, such that insulin prices have become a hot-button issue for patients and patient advocates.

Biosimilars in other therapeutic classes have been competing successfully with reference products and bringing down prices. Prime acknowledged this in its statement: “Biosimilars often have initial prices that are 15% to 35% lower than the reference products, which is particularly important as drug costs continue to increase, and specialty drugs now represent more than 50% of the health care dollar.”

The placement of Semglee on formulary follows a recent Prime announcement that it would increase management of claims to drive broader biosimilar adoption via the launch of a program called “MedDrive.”

“The first phase focuses on drug savings strategies through greater biosimilar drug adoption, most of which are paid on the medical benefit,” the PBM said. “Other elements of the initial program include benefit designs that prefer lowest net cost nonbiosimilar drugs.”

The company contended that “a fragmented approach to managing drugs under the medical benefit” is responsible for obstructing greater adoption of biosimilars.

Prime stated in a recent white paper that its experience with granulocyte colony-stimulating factor (G-CSF) biosimilars and reference products has convinced it that moving biosimilar promotion “into high gear” through preferential formulary strategies is the way to go.

In September 2018 the PBM experimented with G-CSF biosimilars by preferring them in 3 Blue Plan client groups and placing them on equal formulary status with other Blue Plan groups. The result was that the biosimilar preferential policies resulted in significantly higher biosimilar conversion rates (87%, 88%, and 98%, respectively) than for the non–G-CSF biosimilar preferring plans (average, 24%).

“Adding biosimilars to the formulary and preferring them, for even just 3 plans, collectively delivered savings of $4 million in 2019,” Prime said. “If all Prime’s Blue Plan clients prefer biosimilars in the G-CSF space and adoption rates follow, we project savings of $41 million to $55 million a year.”

Prime Therapeutics said that by putting Semglee (insulin glargine) on formulary, along with other biosimilars, it could achieve savings of $41 million or more per year. 

Prime Therapeutics Joins Express Scripts in Moving Semglee to Preferred Formulary Status

As biosimilars become more prevalent in countries across the globe, one question arises: Are the savings from these often lower-cost agents benefiting the health care consumer?

“When competition with biosimilars kicks in, there are no policies supporting the reinvestment of the savings into more patients having access,” said Suzette Kox, general secretary of the International Generic and Biosimilar Medicines Association (IGBA), at a webinar sponsored by the IGBA, a trade group of pharmaceutical developers and manufacturers. The occasion was the launch of a 

 the group called a blueprint for future development of the generic and biosimilar medicines industry.

“It is very complicated indeed how to ensure that the biosimilars which are approved and eventually become available on the market are really benefiting patients and the health care systems,” Kox said.

The problem of how to ensure savings and access appears in different forms. “We have more than 30 biosimilars registered in Brazil, but only 5 of them are available for our population, and these are focused on cancer treatments and rheumatic diseases,” said panelist Gustavo Santos, general manager of medicines and biological products at ANVISA, the Brazilian health regulatory agency.

In markets where many more biosimilars are available, there’s a growing expectation that manufacturers must participate in ensuring that generic and biosimilar availability is supported by “end-to-end solutions” that contribute to improved health outcomes, according to the IGBA white paper.

“Rather than acting as a supplier to this trend, industry should play a central role in developing these solutions….Generics and biosimilar companies should address the full continuum of care and effectively team up with diagnostics providers, health care providers, and technology companies to bring about patient-centric solutions,” authors of the paper wrote.

The white paper described a rapid advancement of biosimilar use over the past 5 years, which it said was supported by streamlining of regulatory guidance and “increasingly positive clinical experience.” In Germany, for example, biosimilar versions of adalimumab, bevacizumab, and rituximab have achieved 72%, 80%, and 85% market shares, respectively, according to the IGBA paper.

“Going forward, the market is expected to see continued double-digit growth with potential for the industry to scale-up significantly,” the authors wrote, but they said that would be conditional upon sustained development of the biosimilar market in the United States with favorable regulatory policy and increasing stakeholder acceptance.

Further opportunities for biosimilar development lie ahead with anticipated loss of exclusivity (patent protection) for multiple originator biologics, by which means biosimilar developers can diversify away from the core biologics that they have relied upon thus far, the authors wrote. More products in oncology and autoimmune diseases are possible.

“As a result, cumulative savings from biosimilars are expected to reach $285 billion globally over the next 5 years, with annual savings exceeding $100 billion in 2025 alone,” the report predicted.

However, the competitive atmosphere is expected to grow more intense.

“Only early entrants [in a therapeutic drug category] have the potential to recover the significant investments made in product development.” Consequent to this, “Biosimilar launches have also witnessed accelerated price erosion curves across markets,” authors of the paper wrote.

They said recent anti–tumor necrosis factor biosimilars have upon launch seen price declines in the neighborhood of 25% when the first biosimilar arrived on market, but when multiple competitors enter the same market and are forced to outbid one another to obtain supply contracts, “erosion can reach up to 70% relatively quickly.”

“The sustained pricing pressure will require stringent containment of operating costs beyond what is bare minimum required by the industry to deliver high quality products, particularly in light of input cost raises,” the authors wrote. They expressed concerns about the long-term consequences of this economic pressure.

For biosimilar penetration into markets in emerging countries, cooperation is needed from regulators. Regulatory frameworks in some cases are not conducive to bringing biosimilars to market, approval processes may be too complex, approval timelines may not be well defined, and clinical study design requirements may be unclear, they wrote.

“While emerging markets represent a traditional growth opportunity and a key playing ground for improved access to medicines, they also present severe competitive and structural market challenges for generics and biosimilars companies,” authors of the report said.

The Center for Biosimilars® recently interviewed members of Medicines for Europe about their comprehensive review of European Union markets for biosimilars. This interview appears in 2 parts, the first of which is available at this 

Kicking off Global Biosimilars Week, the International Generic and Biosimilar Medicines Association (IGBA) released a blueprint detailing hurdles and opportunities for industry progress.

IGBA Describes Competitive Economics of Biosimilars Industry

Pfizer officials said in an earnings call this week that they intend to seek interchangeable status for their adalimumab biosimilar (Abrilada) in a filing with the FDA in December 2021.

Interchangeable status has the potential to boost uptake of the product, which is scheduled to launch against 5 other adalimumab biosimilars in 2023. The interchangeable designation enables pharmacists to make the decision whether to dispense a biosimilar or a reference product rather than having to consult with the prescribing physicians.

Removal of that administrative step is considered a competitive edge for biosimilars, which although approved as being highly similar to reference products, with no clinically meaningful differences in safety or efficacy, don’t automatically receive interchangeable status.

Angela Hwang, group president for the Pfizer Biopharmaceuticals Group, said the company has completed interchangeable studies demonstrating that the adalimumab biosimilar can be interchanged multiple times for the originator product in patients, with no significant change in clinical outcomes.

Abrilada gained FDA approval in November 2019 but has been sitting on the shelf owing to a settlement between Pfizer and adalumumab originator (Humira) maker AbbVie. Most recently, 

, an adalimumab biosimilar also scheduled to launch in 2023, received interchangeable status from the FDA.

Partial earnings were reported for Pfizer’s biosimilars portfolio for the just-ended financial quarter. The company touted a 51% increase in “operational revenues” for its oncology biosimilars portfolio, which totaled $398 million, representing $284 million in US revenue and $98 million non-US revenue.

The company has multiple oncology biosimilars and supportive oncology biosimilars. In the former group are Ruxience (rituximab), Trazimera (trastuzumab), and Zirabev (bevacizumab). These were launched in 2019. The company also has Retracrit (epoetin alfa), Nivestym (filgrastim), and Nyvepria (pegfilgrastim), which enable patients to recover from blood-cell depletion following chemotherapy.

By contrast, Pfizer reported global biosimilar revenues of $424 million in the third quarter of 2020; and in terms of sequential revenues, the company reported global biosimilar operational revenues of $559 million for the second quarter of 2021.

Its biosimilar revenues in the third quarter of 2021 represented a portion of non–COVID-19–related revenues that were up 7%. When revenues for the company’s COVID-19 vaccine business are included, the total represents a 130% increase in revenues compared with the third quarter of 2020. Total third quarter 2021 revenues were $24.1 billion.

“While we are proud of our financial performance, we are even more proud of…what these financial results represent in terms of the positive impact we are having on human lives around the world,” Albert Bourla, chairman and CEO, said in the earnings call. “In the first 9 months of 2021, our innovative medicines and vaccines reached nearly 1 billion people. It's fair to say millions of lives have been saved because of [the COVID-19 vaccine, Comirnaty].”

Bourla said that excluding COVID-19 vaccinations, the company’s medications reached 300 million individuals during that period.

Pfizer reports on biosimilar revenues and says its switching studies for Abrilada, an adalimumab biosimilar, support interchangeable status.

Pfizer to Seek Interchangeable Status for Abrilada Biosimilar 

The month of October brought a mixture of payer, regulatory, and clinical news in biosimilars, and these and more stories were covered by The Center for Biosimilars

One of the top stories was the approval of 

 for the adalimumab biosimilar Cyltezo. This product was originally approved by the FDA as a biosimilar in 2017. Boehringer Ingelheim has projected a launch date of July 1, 2023.

 covered multiple poster and speaker presentations at the Academy of Managed Care (AMCP) Nexus 2021 meeting. In surveys presented at the conference, US pharmacists were found to have an 

 of biosimilars and interchangeability, and patients with immune-mediated disorders were only 

 of these lower-cost-but-equivalent agents.

Also at AMCP, Jeff Casberg, MS, RPh, predicted that “

”— manufacturer biosimilar versions of their own originator products—may soon enter the marketplace to compete against biosimilars.

 of an implantable device for delivery of ranibizumab, which poses a challenge to biosimilar makers. The implantable (Susvimo) requires refilling every 6 months and delivers a steady flow of ranibizumab to the eye. Biosimilars, on the other hand, must be injected into the eye as often as once a month.

, which are now one of its profit drivers, although the company has wrestled with FDA concerns about its Malaysia biologics factory. The company said it has established a plan for correcting the problems the regulatory body has identified.

Basaglar has been on the market since 2016, and although it references Lantus, it isn’t technically a biosimilar; but the presence of this drug has had an important effect on the affordability of insulin glargine, according to a 

. From 2015 to 2020, net prices of Lantus declined by 5.2% per quarter.

It can happen that reference brands end up costing less than biosimilars. Much depends on how aggressive manufacturers are in competing with biosimilars. A specialty pharma report from CoverMyMeds predicted that increasing savings from biosimilar competition could benefit 1.2 million more patients by 2025. The report, however, also charted the rates of prescription abandonment by patients whose medications are priced beyond affordability. At $250 out of pocket, the rate of abandonment is 

Do varying dosage and infusion intervals for infliximab improve outcomes for patients with rheumatoid arthritis and ankylosing spondylitis? Investigators working on the 5-year RAAS study say the answer is an 

. They measured dosage, infusion interval, and combined treatment pattern changes for real-world patients and found the changes reduced disease activity, although survival patterns were not notably different. The agent used in the study was CT-P13.

Lastly, the Biosimilars Forum, a trade association of biosimilar developers and manufacturers, converted biosimilar data from Pacific Research Institute to create a 

 for biosimilar savings. If biosimilar adoption reached a 75% market share (vs reference products) in each state of the union, the total national savings would be $14.08 billion, the group said. The calculator allows users to look up the respective savings for each state based on a 75% utilization rate.

The second interchangeable biosimilar approval, estimates of biosimilar savings, and competition for ranibizumab biosimilars characterized the month's developments. 

Biosimilar October News Roundup: An Interchangeable Biosimilar Approval and More

The arrival of biosimilars in the United States has followed a winding path, which is the result of initial poor acceptance and, lately, the COVID-19 pandemic, which has gummed up the approval and factory inspections process at the FDA.

But 6 years into biosimilar marketing, it’s possible to see progress and resistance on a more granular level, according to Leslie Fish, RPh, PharmD, vice president of pharmacy at IPD Analytics, who spoke about biosimilars at the Academy of Managed Care Pharmacy (AMCP) Nexus 2021 meeting.

Patent barriers are to blame for some of the wet powder in biosimilar launches, limited physician and payer acceptance are other causes, and the intrusion of COVID-19 priorities at the FDA is another. But aggressive marketing by reference product manufacturers to ward off biosimilar success also can claim a role in slowness of biosimilar acceptance in the United States, Fish said.

“When the pandemic arrived, the first thing that happened was that the clinical trials for biosimilars were delayed or postponed, or actually some even stopped totally. You could not get patients in to see their doctors,” she said.

“The FDA had to take all the people who looked at all the biosimilar data and put them into COVID-19 medication review; but the next thing, which was important for all medications that are in the pipeline, is that the FDA could not get into plants to do manufacturing inspections. In fact, that’s still delayed,” she said.

Not a lot was known about biosimilars 6 years ago when they debuted, Fish said. Biosimilars entered the market at prices much higher than some may have expected. This may have been because people were primed to expect the same thing to happen for biosimilars as happened for generics, which arrived in some cases at discounts of 60% to 70% off the originator brand prices. “It wasn’t near there at all,” she said.

Partly, this was because there was less competition and biologics are costly to develop and manufacture—as much as $200 million for an individual biosimilar, according to an Amgen estimate.

I’ve been going to the American Society of Clinical Oncology meetings for years, and 5 years ago there must have been at least 3 or 4 different biosimilar lectures. And every year since then there have been lots of biosimilar lectures during those meetings,

“But back in 2015, 2016, there was not a lot of education,” Fish said. The FDA and CMS eventually began educating the public more broadly about biosimilars.

One thing that happened was that oncologists were among the first adopters, and to this day they are the most enthusiastic, as a group, about biosimilars, judging by their embrace of these agents. Fish said oncologists are well educated about biosimilars, have a favorable view of them, and have adopted them at a rapid pace.

“I’ve been going to the American Society of Clinical Oncology meetings for years. Five years ago, there must have been at least 3 or 4 different biosimilar lectures. And every year since then there have been lots of biosimilar lectures during those meetings,” she said.

By comparison, rheumatologists also are well educated about these agents, but are moderately favorable in their view of them, and uptake has been slow, Fish said. Gastroenterologists are at the tail end of the adoption curve, being moderately educated on biosimilars, possessing unfavorable views of them, and being slow about adopting them.

Another brake on the progress of biosimilars has been the web of contracts, rebates, and revenue streams between manufacturers and payers and clinical institutions, which in combination with a lack of payer management of prescription practices has stunted the development of this market, Fish said.

“So, you see a biosimilar on the market, but not a lot of utilization. You also could see it being put on formulary, but there are no step therapies,” she said.

Payers may be slow to adopt biosimilars, may cling to manufacturer rebates for originator products, or may jump into biosimilars and suffer the uncertainty of unclear financial benefits of doing so, she said. “That sort of middle, in-between area is that the payer will put a biosimilar on formulary but won’t take the reference product off.”

Payers may only dip a toe into the biosimilar pond by tweaking their policies just a little, such as by requiring a smaller co-pay for the biosimilar, which Fish described as “semimanagement.” More recently, the payer stance toward biosimilars has been characterized by aggressive management. “You see formularies that are going to get whittled down if there is more than 1 biosimilar product.”

But this form of management may assume an odd shape, she said, because payers may put a few biosimilars and their reference product on formulary, or just a brand and a biosimilar, or 2 biosimilars, she said.

Fish reviewed some of the trends in individual biosimilar adoption. Infliximab biosimilars accounted for just 11% of market share in mid to late 2019, and even by the end of the second quarter of 2021, the originator product, Remicade, held a 75% share, she noted.

The story is better for short-acting filgrastim (Neupogen), she said. The biosimilar Zarxio had a 57% share of the market in the third quarter of 2019, vs 40% for Neupogen, and by the second quarter of this year, the originator held just a 26% share of the market.

Long-acting filgrastim (pegfilgrastim) biosimilars have taken an incrementally larger share of the market from Neulasta and its wearable injector version (Neulasta Onpro). Starting in the third quarter of 2019, the reference drug held just a 55% share of the market, and that declined to 52% by the second quarter of 2021, Fish said. Those are still large shares of the market for biosimilars.

“What really makes it interesting is that pegfilgrastim biosimilars are not just against Neulasta, but against Neulasta Onpro,” Fish said. “So, this is different than we were anticipating what the utilization of pegfilgrastim was going to be. We began looking at the utilization, and we saw a very big uptake against both the on-body applicator and the regular version of Neulasta.”

The manufacturer had tried to convert everybody to the on-body applicator and they were doing an amazing job of that.

“Besides that, the manufacturer had tried to convert everybody to the on-body applicator and they were doing an amazing job of that,” she said.

A more traditional—or predictable—uptake curve has been seen in use of rituximab biosimilars. Fish noted that from 100% use of the originator brand, Rituxan, in the third quarter of 2019, biosimilars had assumed a 53% share of the market by the second half of 2021.

Rituximab is used in oncology and rheumatology, but it has been better received among oncologists, Fish said. However, the more recent market share numbers indicate that rheumatologists are picking up the biosimilar versions of rituximab.

The same pattern is seen for the bevacizumab market, which was dominated by the originator brand in the third quarter of 2019 (96%). By the second half of 2021, the reference brand share was 32%. Fish estimated cumulative bevacizumab biosimilar savings of $1.4 billion in the United States.

An almost identical biosimilar trajectory is notable in trastuzumab, where the reference brand went from a 96% share in the second half of 2019 to a 32% share by the middle of 2021, with cumulative savings of $2.5 billion, Fish said.

Epoetin alfa biosimilars have followed a relatively flat trajectory since mid-2019, according to Fish. Starting from a 41% market share, they now represent 44% of the market.

It’s important to note that the average sales prices (ASPs) for biosimilars and reference products have been decreasing over time, so the competition has stopped the upward march of reference product prices and resulted in savings for both reference products and biosimilars, Fish said.

The trastuzumab reference product (Herceptin) had seen a 15% ASP drop by mid-2021; Avastin (bevacizumab), 13%; Rituxan, 8%; Neulasta, 47%; Neupogen, 3%; Epogen/Procrit (epoetin alfa), 37%; and Remicade, 50%, according to Fish’s figures.

Payers have moved from toe-in-the-water biosimilar policies to aggressive management, contributing to much more robust savings in recent years, according to Leslie Fish, RPh, PharmD, vice president of pharmacy at IPD Analytics. 

IPD Analytics Executive Offers Perspective on Biosimilar Uptake and Policy

Has Roche developed a viable defense against ranibizumab biosimilar competition for Lucentis, the company’s product for neovascular age-related macular degeneration (wet AMD)?

The FDA’s approval last week of Roche’s ranibizumab implant (Susvimo) offers patients convenience as well as an alternative to monthly injections.

Until now, ranibizumab administration has involved eye injections as often as monthly. Susvimo is implanted in the eye and contains a reservoir of ranibizumab good for 6 months. For patients looking at 12 monthly treatments vs just a Susvimo implant and refill over the span of a year, the latter may seem the better way to go.

And the significance for biosimilar competition could be meaningful. Just in September 2021, Samsung Bioepis and Biogen’s ranibizumab (Byooviz) became the first ranibizumab biosimilar to gain FDA approval, and the companies do not plan for commercialization of their product before June 2022, owing to a licensing agreement with Roche.

This would allow Susvimo a chance to become established in the marketplace, and before patients are ever offered monthly injections of biosimilar ranibizumab, many may be well accustomed to the twice-yearly treatments with Susvimo.

Their willingness to switch to potentially more-affordable biosimilars on a monthly injection regimen will be put to the test.

Although Byooviz is the only ranibizumab biosimilar with FDA approval, there are several more in the pipeline. These include Xlucane, an Xlucane/Bausch biosimilar candidate in phase 3 trials; LUBT010, a Lupin product candidate also in phase 3; and FYB201, from Coherus BioSciences and Bioeq. A biologics license application for FYB201 has been accepted for review by the FDA. So, with a new method of administration entering the marketplace, there is much at stake for these companies.

Coherus BioSciences and Bioeq are anticipating action by the FDA on August 2, 2022, and if the biosimilar is approved, they plan to launch in the United States in the second half of that year.

The Susvimo impact may also reach beyond ranibizumab to other treatments commonly used for the treatment of macular degeneration. Aflibercept (Eylea) also is injected monthly for treatment of these conditions, and bevacizumab (Avastin) is used off-label in the same way.

There are as many as 8 aflibercept biosimilars under development, many of them in phase III development; however, there has been pushback from the ophthalmology community about the use of bevacizumab biosimilars for eye conditions.

Susvimo delivers ranibizumab into the eye continuously, and while Roche doesn’t guarantee that patients will need just 2 treatments (refills per year), the company boasts that Susvimo has that potential. The product is indicated for patients who have previously responded to at least 2 anti–vascular endothelial growth factor (VEGF) injections.

“Susvimo represents a major advancement in the treatment of retinal disease and is an important new option for patients with wet AMD,” said Carl Regillo, MD, chief of Retina Service at Wills Eye Hospital in Philadelphia and an investigator in the pivotal phase III Archway study that led to the product’s approval.

“With Susvimo, my patients now have an option that can help them maintain their vision as well as anti-VEGF injections, but on a more manageable twice-yearly treatment schedule,” he said.

The Archway study demonstrated that patients with wet AMD treated with Susvimo achieved and maintained vision gains equivalent to those achieved with monthly ranibizumab eye injections. That equivalency was defined as gains of 0.2 to 0.5 eye chart letters from baseline by weeks 36 and 40 of treatment, respectively.

Roche said that only a small percentage (1.6%) of patients receiving Susvimo needed supplemental ranibizumab treatment prior to the first scheduled refill at 6 months.

Despite the convenience, some patients may prefer to stick with monthly ocular injections. Investigators reported a “3-fold higher rate” of endophthalmitis with Susvimo than with monthly injections. Endophthalmitis is an infection inside the eye and is considered a medical emergency. “In clinical trials, 2.0% of patients receiving a ranibizumab implant experienced at least 1 episode of endophthalmitis,” authors of the study reported.

 of the incidence of endophthalmitis related to intravitreal injections of bevacizumab and ranibizumab noted an overall rate of endophthalmitis of .02%, or an incidence of 1 in 4500 injections, based on a study of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab.

The most common adverse events associated with Susvimo in Archway were conjunctival hemorrhage, conjunctival hyperaemia, iritis, and eye pain. “The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely,” Roche said.

The company has further trials of this product under way, including the Velodrome study, which is evaluating Susvimo refilled every 9 months (instead of 6) in wet AMD. The studies will elucidate the value of Susvimo for treatment of diabetic macular edema and diabetic retinopathy.

Roche intends to launch the product “in the coming months.”

The Center for Biosimilars® interviewed George Williams, MD, clinical spokesman for the American Academy of Ophthalmology, about the ranibizumab biosimilar 

the bevacizumab biosimilar intravitreal controversy.

The arrival of Susvimo, an ocular implant for treatment of macular degeneration, poses a challenge for ophthalmic reference products and biosimilars. 

Roche's Susvimo Represents a Challenge for Ranibizumab Biosimilars

The FDA has approved 2 interchangeable biosimilars—biosimilars that pharmacists could substitute interchangeably with reference drugs—since July 2021, but manufacturer-developers are seeking interchangeable status for about 7 other biosimilars, according to Jeff Casberg, MS, RPh, vice president of Clinical Development for IPD Analytics.

Casberg participated in a presentation on interchangeable biosimilars at the recent Academy of Managed Care Pharmacy Nexus 2021 meeting in Denver, Colorado.

Interchangeables are potential game changers, but also looming is the possibility of “authorized biologics,” or agents that product manufacturers develop as nonbranded copies of their original drugs, he said.

The theory is that reference product manufacturers will launch authorized biologics to compete against biosimilars and prevent loss of revenues and market share. Presumably, authorized biologics, like biosimilars, would launch at discounts to their reference products. There are no authorized biologics yet, but that seems likely to change soon, Casberg said.

The winners in this stuggle may simply be the lowest-cost drugs, he said.

When it comes to pharmacy and therapeutics (P&T) committees and the choice of which drugs are used in health care institutions, the interchangeability designation has some advantage over straightforward biosimilar status, Casberg said. “Realistically, it’s going to come down to cost, but I think interchangeability could be a tiebreaker.”

For some large institutions, it won’t matter whether it’s an interchangeable or not, he said, “if you’re in a hospital or clinic type of facility, you probably don’t need the interchangeability designation. There are policies that guide which products you can interchange as a pharmacist."

“Authorized biologics are interchangeable. They are the same drug, and we don’t call them 'authorized biosimilars.' We call them authorized biologics because calling them authorized biosimilars would suggest biosimilars aren’t quite the same drug, so we call them authorized biologics,” Casberg said.

“Today, we haven’t really seen brand companies have the motivation to bring these authorized products to market, but I think you’ll start to see a few in the future,” he said.

The drug pipeline is stocked with more potential interchangeables. Semglee, an insulin glargine, that received biosimilar and interchangeable status in July 2021, is a type of a hybrid. It was originally approved in 2020 via a new drug application rather than through the biosimilar regulatory pathway. It references Lantus.

Biocon Biologics and Viatris aim to relaunch Semglee with its interchangeable status and in vial form by the end of the year, at a 5% discount to Lantus and a wholesale acquisition cost (WAC) of $26.94, according to Casberg. However, the goal is also to launch Semglee as an authorized biologic in vial and prefilled syringe versions at a 65% discount to brand, or a WAC of $9.87.

That means Biocon Biologics and Viatris are playing the interchangeable and authorized biologic games with the same product, he said.

Authorized biologics are interchangeable. They are the same drug, and we don’t call them authorized biosimilars. We call them authorized biologics because calling them ‘authorized biosimilars’ would suggest biosimilars aren’t quite the same drug, so we call them authorized biologics.

Competitors in the field of adalimumab and insulin products may soon include “authorized biologics” in addition to biosimilars and interchangeable biosimilars, a pharmacy expert explains at the Academy of Managed Care Pharmacy Nexus 2021 meeting. 