Pfizer Gets FDA’s Green Light on Its Filgrastim Biosimilar

Pfizer's Biosimilar Filgrastim
FILE PHOTO – The Pfizer logo is seen at their world headquarters in Manhattan, New York, U.S., August 1, 2016. REUTERS/Andrew Kelly/File Photo

On July 20, the US Food and Drug Administration (FDA) approved the second biosimilar version of filgrastim. Pfizer’s filgrastim biosimilar is named Nivestym™ (filgrastim-aafi).

The originator product, Amgen’s Neupogen®, has steep competition from two other products (Sandoz’s Zarxio® [filgrastim-sndz] and Teva’s Granix® (tbo-filgrastim]). Granix was approved as a follow-on biologic, before the biosimilar pathway was implemented.

The FDA granted Nivestym the following indications:

  • To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.
  • For reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).
  • To reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT).
  • For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
  • For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

Although a launch date was not announced for Pfizer’s filgrastim biosimilar, the company’s press release stated that “Nivestym is expected to be available in the US at a significant discount to the current wholesale acquisition cost (WAC) of Neupogen.”

Rather than competing aggressively for the filgrastim market, Amgen seems to be focusing its efforts on its pegfilgrastim brand, a longer-lasting version. Specifically, it is seeking to move its utilization to the Onpro formulation of Neulasta®. The first biosimilar to pegfilgrastim was approved in June (Mylan and Biocon’s Fulphila™).

Would Biosimilar Approvals With Limited Indications Alter the IP Discussion?

Over the next couple of weeks, I’ll be issuing a series of posts to further analyze some of the Food and Drug Administration’s (FDA’s) new Biosimilars Action Plan.

The Biosimilars Action Plan contains several important components. One of the more interesting items FDA Commissioner Scott Gottlieb mentioned in his remarks at the Brookings Institution webinar on Wednesday, July 18, involved modifying the intellectual property (IP) discussion with biosimilar approval for limited indications.

Originator drug makers have erected a so-called patent maze or patent wall over time to protect their IP and thus their marketing exclusivity as far into the future as possible. Patents can be filed for product composition, manufacturing techniques, new formulations, delivery systems, and indications. Often, the biologic products facing potential biosimilar competition have several indications. Adalimumab, for instance, is approved for use in nine unique conditions (I’ve included Crohn’s disease and pediatric Crohn’s as one disease state).

Dr. Gottlieb said that the FDA will be “updating guidance to provide additional clarity on how biosimilar manufacturers can carve out indications from their labels where a branded drug maker might still maintain some IP.” He continued, “And we’re going to describe how these indications can be efficiently added into a biosimilar label once that IP on the branded alternative has lapsed.”

This component was not spelled out in the Biosimilars Action Plan. Limited indications may indeed be an avenue to work with originator manufacturers to help reduce patent litigation that is barring patient access to biosimilars. One would assume that it would take some level of negotiation with the manufacturer of the originator. However, biosimilars with limited indications may be a hornets’ nest for reference manufacturers like AbbVie.

This gets back to the entire issue of extrapolation. From the outset, patients and providers recoiled at the notion of approving a biosimilar product for use in a disease state in which no clinical studies were done. The FDA has been pretty liberal in granting extrapolation to several or all indications for the 11 approved biosimilars. If FDA explored this option as a mechanism for getting biosimilars to the market sooner, it would be sending a new message. That is, the biosimilar drug may be expected to yield similar outcomes compared with the reference drug based on the totality of the evidence, but we’re unwilling for other reasons to give it our approval for those other indications.

Biosimilar Indications Laws or regulations do not exit to prevent doctors from prescribing a biosimilar for a nonapproved indication. Furthermore, health plans and insurers have consistently reported in our own market research that they would not discourage use of a biosimilar for other indications for which only the originator biologic was approved. This assumes the biosimilar is sufficiently less expensive than the originator. As a result, drug makers like AbbVie may be very wary of the limited-indication approach to improve biosimilar access.

Still, some way must be found to break the logjam of litigation on IP. This is a specific target of Commissioner Gottlieb’s. He may take even more creative approaches.







FDA Commissioner Gottlieb Announces Biosimilars Action Plan

Realizing that something is very wrong with the speed of biosimilar access and uptake in the United States, Food and Drug Commissioner Scott Gottlieb announced a plan to address multiple factors slowing competition in these markets. He introduced his Biosimilars Action Plan in a webcast today hosted by the Brookings Institution.

“While less than 2% of Americans use biologics, they represent 40% of total spending on prescription drugs,” said Dr. Gottlieb.
“So, enabling a path to competition for biologics from biosimilars is a key to reducing costs and to facilitating more innovation.”

He stated, “Our Biosimilars Action Plan has 4 key strategies: Biosimilars Action Plan(1) improving the efficiency of the biosimilar and interchangeability development and approval process; (2) maximizing scientific and regulatory clarity for the biosimilar product development community; (3) developing effective communications to improve understanding of biosimilars among patients, clinicians, and payors; and (4) supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition.”

The following specified elements of the Biosimilars Action Plan are taken directly from FDA’s website:

  1. Developing and implementing new FDA review tools, such as standardized review templates that are tailored to marketing applications for biosimilar and interchangeable products, to improve the efficiency of FDA review and enhance the public information about FDA’s evaluation of these products.
  2. Creating information resources and development tools for sponsors of biosimilar applications. This includes tools such as in silico models and simulations to correlate pharmacokinetic and pharmacodynamic responses with clinical performance. Such tools can make biosimilar drug development more efficient.
  3. Enhancing the Purple Book to include more information about approved biological products, including information relating to reference product exclusivity determinations.
  4. Actively exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non-U.S.-licensed comparator products in certain studies to support a biosimilar application.
  5. Establishing a new Office of Therapeutic Biologics and Biosimilars to improve coordination and support of activities under the Biosimilar User Fee Act (BsUFA) program, accelerate responses to stakeholders and support efficient operations and policy development.
  6. Building on the FDA’s Biosimilar Education and Outreach Campaign, continue providing critical education to health care professionals, including releasing a series of videos that explain key concepts about biosimilar and interchangeable products.
  7. Publishing data and information should be included in the labeling.
  8. Providing additional clarity for product developers on demonstrating interchangeability, including by publishing.
  9. Providing additional clarity and flexibility for product developers on analytic approaches structure and function to support a demonstration of biosimilarity, including by publishing revised draft guidance on the use of data analysis methods, including statistical approaches.
  10. Providing additional support for product developers regarding product quality and manufacturing process, including by identifying physical product quality attributes that are most critical to evaluate, and by exploring ways to reduce the number of lots of the reference product required for testing.
  11. Engaging in a public dialogue through a Part 15 hearing and opening a docket to request additional information from the public on what additional policy steps the FDA should consider as we seek to enhance our biosimilar program.

In the coming days, we’ll analyze some of these elements and how they might (or might not) move the needle on biosimilar approval, marketing, and access.


Contracting “Schemes” to Prevent Biosimilar Infliximab Access: Let’s Drop the Feigned Outrage

biosimilar infliximab
Claude Rains as Captain Renault in “Casablanca”

Captain Renault, chief of police in Casablanca, famously uttered, “Rick, I’m shocked! Shocked that gambling is allowed in this establishment,” as he pocketed his winnings. Similarly, no one connected with the pharmaceutical industry, health plan, insurance, or pharmacy benefit management (PBM) sectors should be the least surprised about the controversial practice employed by Janssen Pharmaceuticals to protect marketshare of its reference infliximab product (Remicade®). These same sectors have been pocketing their winnings for decades.

Pharmaceutical Rebate Roulette

The newswire buzzed in mid-June with the lawsuit filed by Walgreens and Kroger in the District Court of Eastern Pennsylvania. They claimed that Janssen’s parent (Johnson & Johnson) engaged in exclusionary practices to prevent access to infliximab biosimilar agents by Celltrion/Pfizer (Inflectra®) and Samsung Bioepis/Merck (Renflexis®). Hold on a second. Walgreens had previously owned a PBM and is now partnered with Prime Therapeutics, a PBM owned by Blue Cross Blue Shield plans, which benefited from the exclusionary rebate model that is the subject of its lawsuit. Kroger also owns a PBM, called Kroger Prescription Plans. Who are they thinking of, patients or themselves?

Pfizer is complaining about Janssen’s “anticompetitive practices” even though that manufacturer participated in similar actions to protect Lipitor® marketshare from the onset of generics. Pfizer can significantly drop its price, undercutting Janssen, which would result in lower net costs for plans and patients, in addition to increased marketshare for the biosimilar.

Exclusionary Contracting Nothing New

The whole point of rebates for payers is to leverage better net prices for these organizations in exchange for greater marketshare and preferred positioning for the pharma companies. Preferred positioning means a medication is available at the preferable formulary tier (with lower patient cost sharing) of products in the same class. So, if that if you agree to give my product preferred tier placement on formulary, I’ll expect that my marketshare will increase compared to noncontracted products These rebate contracts can be pretty weak: for example an “access” rebate of 5% or 10% if a plan agrees not to exclude coverage for the drug. On the other hand, they can be fairly aggressive: for a larger rebate, you agree that my drug will be the only drug of my therapeutic class competitors on the preferred tier (i.e., a “1 of 1” contract) or one of only 2 drugs on the preferred tier (i.e., a “1 of 2” contract). The lawsuits by Pfizer, and Walgreens and Kroger claim that Johnson & Johnson engaged in this 1 of 1 contract, which by its nature is exclusionary.

Multiple sources reporting the initial lawsuit also pointed to Janssen’s “Biosimilar Readiness Plan,” which was implemented with the Food and Drug Administration’s approval of Inflectra®. The Plan was simply its blueprint for negotiating the contracts to stave off the loss of marketshare after its 18 years without any direct competition. The problem was that it was too successful, limiting both Inflectra and Renflexis to single-digit shares of the infliximab market. This raised eyebrows at FDA, with Commissioner Gottlieb calling on plans to wean themselves off their reliance on rebate revenue.

Johnson and Johnson’s strategy to hold off the biosimilar infliximab market is little different than what other manufacturers do and have done for a very long time with their own drugs nearing patent expirations. Sometimes, they go the “authorized generic” route, striking a deal with another manufacturer to license the new product, thus allowing the favored generic manufacturer to launch earlier. They then provide a percent of revenues as a licensing fee back to the branded drugmaker. Other times, they sell their product to a generic manufacturer, knowing that the price will drop greatly when others enter the marketplace. However, in situations where the revenue stream can remain pretty high, even with competition, they will increase the size of the rebates to meet the lower retail price of the new products. This is the case with high-priced biologics. Johnson & Johnson will not want to cede billions of dollars in revenue without some aggressive tactics.

Lack of Price Transparency the Underlying Issue

One underlying problem that is being increasingly publicized is the lack of transparency in these rebate contracts. They are notoriously confidential. No one but the individual plan/PBM and manufacturer know the drug’s net price after rebates. One deal with Kaiser Permanente may be different from a contract with Cigna. Health plans that rely on PBMs to negotiate with manufacturers don’t often know the terms of the contract between the PBM and the drugmaker. In other words, they know they will get a specific amount of rebate revenue back, but may be unaware of the percent of the rebate that PBMs are keeping for themselves.

Adding to the complexity, Remicade (or an infliximab biosimilar) is most commonly covered under the medical benefit, which means it could be subject to a buy-and-bill arrangement with the physician or infusion center providing the infusion. On the other hand, some plans may be trying to move infliximab coverage to the pharmacy benefit, where they feel they can better control costs and utilization. Let’s also not forget that under the average sales price (ASP) method of reimbursement, the ASP is based on costs, discounts, and rebates. In other words, the more a product is rebated, the lower the ASP paid over time.

Why not Just Compete?

Overall, the lawsuits have shone a light on the “dark matter” of price transparency. That’s a good thing. Whether the plaintiffs ultimately win the lawsuit based on the anticompetitive effects of the practice will likely not immediately affect the marketshare of the biosimilar infliximab makers. Of course, the biosimilar manufacturers can simply lower their selling price or offer greater rebates to undercut Janssen. Almost all of these rebate contracts have clauses permitting one party to terminate it within a short notification period. No plan is married to the exclusionary contract. Unfortunately, divorcing themselves from the manufacturer’s rebates is something else. And biosimilar manufacturers fear a “race to the bottom” in pricing. However, this sounds less like competing, and more like complaining.

Captain Renault would have been very comfortable policing this ambiguous, deceptive environment.


Biosimilars Action Plan to be Unveiled by FDA’s Gottlieb

Next Wednesday, July 18, has been set as the rollout date for Food and Drug Administration Commissioner Scott Gottlieb’s new plan to help bring biosimilar drugs to the market sooner. So far, Commissioner Gottlieb has revealed some broad strokes regarding the content of the Biosimilars Action Plan, but the exact measures it contains remain a mystery.

In a series of tweets on Sunday, he stated, “We will soon unveil a comprehensive Biosimilars Action Plan that will include policies and actions to improve the efficiency of FDA’s review of biosimilar marketing applications and increase regulatory certainty for biosimilar manufacturers and other stakeholders.”

Gottlieb announces Biosimilars Action PlanHe indicated that it will consist of education on biosimilars as well as “reducing gaming that may delay market competition.” Outside of taking action to prohibit “authorized generic” agreements, tools that he can use may be somewhat limited, without legislative action.

Dr. Gottlieb also pointed to “providing clarity for product developers via guidance and meetings.” This may have been prompted by the recent withdrawal of a guidance on statistical analysis. The guidance had drawn the ire of biosimilar advocates. Questions still loom over the question of interchangeability and the requirements for approval. This still clouds one of the most promising pathways for biosimilar adoption.

Much has been written about harmonizing international biosimilar regulatory policies, and one wonders whether Commissioner Gottlieb’s call on this will put enough wind in its sails to get underway.

“Although there are barriers to marketing biosimilars outside FDA’s purview,” Dr. Gottlieb tweeted, “we’re committed to advancing policies to facilitate efficient development, approval of biosimilars to reduce costs, enhance access, without reducing incentives to innovate. #BAP will advance these goals.”

For those interested in hearing Dr. Gottlieb introduce his Biosimilars Action Plan first hand, please visit

What Biosimilar Topics Most Interest You?

In my BR&R posts, I’ve written less these days on new clinical study data demonstrating similar patient outcomes. As more biosimilars are approved for marketing by the Food and Drug Administration (FDA), reports of positive clinical trial results seem a bit rote.

Like successful space launches, routine expectations begin to set in—until something goes wrong. Of course, news about a prospective biosimilar not meeting its clinical study goals is news. That also applies to the recent story of Momenta’s abatacept biosimilar, whose phase 1 trial surprisbiosimilar topics surveyed scientists by not demonstrating pharmacodynamic similarity to the originator product.

But it made me think that perhaps the biosimilar topics that compel me to write do not align with what you want to read. I’d like to gauge what you are most interested in reading about biosimilars.

I’m offering two $20 Starbucks gift cards, chosen at random, to people who complete this 5-minute survey. Hopefully, it will enable me to understand where your key biosimilar interests lie.

The survey closes early next week, so please click now at

Let’s not Knock Innovation, but Biosimilars Exist for the Sake of Competition

A recent Twitter conversation between a blogging colleague of mine and a German advocate of precision medicine propelled this post: What is the real benefit of biosimilars? Does biosimilar development detract from efforts to produce innovative medicines? Is the main societal benefit biosimilar cost savings?

biosimilar cost savings

Biosimilar Development Is Separate From Innovation Development

The main reason that the Biologics and Biosimilars Price Competition and Innovation Act (BPCIA) was signed into legislation was related to cost containment. For biologics, there was no pathway for the evaluation and approval for lower-cost copies in the US health system, akin to the generic-brand name dynamic for conventional drugs. Adding competition has been the first and only point. The specialty drug trend had been rising rapidly, and the long-term estimates were frightening: Costs associated with specialty drugs like biologics threaten to eat 48% of the total drug spending pie in the United States by 2020.

Two factors were responsible. The first, increasing specialty drug utilization, has been especially difficult to address. The pipeline is congested with biologics. Medical societies are increasingly incorporating biologics into their guidelines and clinical pathways. Prescribers have grown more comfortable with these agents, and payers have limited tools at their disposal to put the brakes on their use.

The second, price increases, are well known and publicized. Without competition, drug companies tend to test what the market will bear, and to this point, they have borne quite a bit. Unlike in Europe, where the tender system of pharmaceutical purchasing has resulted in better cost containment, the US payers have been accustomed to stomaching large price increases through increased use of rebate contracts with price guarantees. But the overall costs continue to rise, as contracts expire and new ones are drawn up. Thus, the list prices for drugs like Enbrel® and Humira® have skyrocketed, with Humira’s more than doubling in a few years.

There is no evidence to say that biosimilar manufacturers would have engaged in the development of innovative new agents had they not devoted resources to this area. Indeed, pure-play biosimilar makers, like Coherus or Adello, were only introduced to produce biosimilars. Other makers, such as Samsung Bioepis, are joint ventures of existing manufacturers to do the same. Biogen recently raised its stake in Samsung Bioepis to nearly 50% of the company’s shares. This could be construed as a case of an originator company pouring $700 million into a biosimilar manufacturer, which could be using that money directly for other purposes. Finally, firms like Apotex, Mylan, Sandoz, and Hospira (now part of Pfizer) are heavily involved in generic drug manufacturing. Biosimilar development was a natural extension for them. Even big pharma players, such as Amgen, Merck, and Pfizer, are more commonly engaged in biosimilar marketing partnerships rather than purely R&D efforts (e.g., Amgen/Allergan, Merck/Samsung Bioepis, Pfizer/Celltrion).

One can also make an argument that pharmaceutical innovation is more evident at the drug discovery level. These days, big pharma seems less interested in pursuing drug discovery than in purchasing it.

The Societal Benefits of Biosimilars

The EMA and FDA biosimilar pathways were created to introduce competition that would lower drug costs. This in turn would make innovative biologic therapy available to more patients. Biosimilar cost savings could drive greater access to important drug technologies.

With the EU’s longer and more extensive experience with biosimilar medications, costs have indeed been saved. Although this has varied by country, it is undeniable.

In the US, with very limited economic experience with biosimilars (filgrastim and infliximab), savings figures are more theoretical than real. Although the infusion of a biosimilar into the new market may reduce wholesale acquisition price of the reference drug a bit, it will have a greater effect on net pricing, after rebates. And, of more immediate importance, the new biosimilar has the potential to halt further price increases for the originator product. This aspect of biosimilars cost savings cannot be overemphasized. Between the first adalimumab biosimilar approval and the initial availability of these products in 2023, the list price of Humira can increase upwards of 40% (or more, if Abbvie veers from its pledge to limit price increases). The initial price of the first adalimumab biosimilar will thus be much higher than if it was launched last year. On the other hand, adalimumab biosimilars will launch in the EU in October of this year, which should effectively lower cost products and limit their EU members’ exposure to future Humira price increases.

Biosimilar cost savings can have real benefits in terms of improved access. Payers’ incentives to use biosimilars (if they are motivated to implement them) can result in lower patient cost sharing. For example, a fourth-tier biologic may be subject to a 20% cost share, whereas a third-tier biosimilar may carry a flat copay of $100. This can make a difference in terms of therapeutic choices available to patients.

In conclusion, the German correspondent is only partly right. Biosimilars are not innovative. They are highly complex, cost-control medications. Do they detract the focus of manufacturers from new innovative products? There’s no evidence of this. However, we are beginning to see limited evidence in the US of the societal benefits, namely cost savings, they can bring.

An FDA Filing for Momenta’s Adalimumab Biosimilar Coming Soon?

Momenta seems to be in final preparations for its first 351(k) filing to the Food and Drug Administration (FDA). In its recent investor conference, the company disclosed that it is ready to send M923, its adalimumab biosimilar, to the agency for approval.

Momenta's Adalimumab Biosimilar
Craig Wheeler, CEO of Momenta Pharmaceuticals

Despite this promising news, Momenta is facing strong headwinds. Even if it gains approval, Momenta expects that the US launch of the adalimumab biosimilar will not occur until 2023, owing to pending patent issues with Abbvie’s Humira®. The company does not yet have a marketing partner for this agent, though there appears to be plenty of time.

In addition, Momenta received a setback in November 2017 on another looming biosimilar candidate, when its biosimilar version of abatacept failed its phase 1 trial. Apparently, its M834 produced pharmacokinetic results that differed from the originator Orencia® in this early clinical study. Momenta is still studying the data and trying to come to grips with the surprising findings.

The company is also set to begin “pivotal” clinical trials on its other drug candidate M710, a biosimilar to aflibercept. The originator product is Eylea®, and it is indicated to treat wet age-related macular degeneration.

Momenta’s partnership with Mylan is moving forward with preclinical work on four other nonspecified biosimilars, according to the company. But all of this development costs money, and Momenta has acknowledged that it may need to raise cash for future development.

Momenta received approval in January for a generic form of the multiple sclerosis drug Copaxone® (glatiramer acetate). The approval of this agent, produced in partnership with Sandoz, had been delayed because of manufacturing issues. The company recognizes that the entry of Mylan (ironically) into this market may hinder its financial outlook.

As a result of these developments, Momenta stated it would entertain a sale of its adalimumab biosimilar “or other assets.”


The Patent Games: Another Sequel Underway

Roche/Genentech has filed suit in Delaware, citing the alleged violation of 37 patents by Amgen in its intent to market its biosimilar version of Herceptin®.  

The litigation was filed in response to Amgen’s stated intention of launching their product in October 2018, based on a May approval. Unfortunately, the Food and Drug Administration decided not to approve Amgen and Allergan’s initial 351(k) application in early June.

Roche has been engaged with Pfizer and the team of Celltrion and Teva on their trastuzumab biosimilars as well.

Infliximab Biosimilars Savings Could Exceed $400 Million Dollars Annually

Everyone with an opinion believes that biosimilar drug use will save the health system considerable money. Calculations for biosimilar savings have been hampered by several factors. For example, previous high estimates have not been based on real-life scenarios. Only 3 biosimilars have been launched and utilized in the US; so little experience has been gained on which to base calculations.

Yet, isolating the savings associated with a single approved biosimilar does put their potential into perspective. It also demonstrates the promise of cumulative biosimilar savings with their launch and uptake. Based on current infliximab average sales prices (ASPs), wBiosimilar Savingshich considers discounts and rebates, one organization believes that a 50% marketshare for biosimilar infliximab could result in well over $400 million in annual savings system wide.

The analysis, conducted by Wayne H. Winegarden, PhD, Senior Fellow in Business and Economics, Pacific Research Institute, accrued the lion’s share of the annual savings to employer-sponsored health plans ($262 million to $315 million, compared with no sales of infliximab biosimilars). Medicare accounted for up to $150 million savings annually.

Dr. Winegarden tested several scenarios. The calculation considered the cost of the infliximab regimen based its various indications. He calculated biosimilar savings using different add-on percentages to ASP (including the current ASP + 4.3% payment and up to ASP + 20%), as well as different marketshares of the biosimilars (from 10% to 90%).

The current marketshare of the two available infliximab biosimilars—Inflectra® and Renflexis®is below 5%, based on data from the first quarter of this year. This is partly because of Janssen’s tactics in matching the net costs of biosimilars with additional rebates on Remicade. This raises two important points: Dr. Winegarden’s analysis reveals savings accruing to the health care system (not necessarily to the payer). Also, the very existence of infliximab biosimilars has resulted in significant net savings compared with the price increases seen prior to their introduction.

It is a bit more difficult to pinpoint the system savings resulting from the use of the first biosimilar approved in the US, filgrastim-sndz (Zarxio®). The other branded product, tbo-filgrastim (Granix®), was launched a couple of years earlier and gained its own marketshare from the reference brand Neupogen®. No doubt, Zarxio contributed to some level of cost savings. In other words, the infliximab example is an easier calculation with a cleaner result.

With eight biosimilars for six reference products awaiting their turn to hit the market, and drugs like adalimumab and etanercept among them, it is easy to see how biosimilars savings can easily exceed $10 billion. Just not yet.

Is Celltrion Paving a New Road for Biosimilars? A New Route of Administration Being Tested for Infliximab

When payers, patients, or physicians discuss biosimilars, they assume that the biosimilar works just like the reference product. They also assume that the biosimilar is administered in the same way as the originator biologic. Celltrion is actively researching a new subcutaneous infliximab. This could result in a first for the biosimilar industry.

Sponsored by Celltrion and conducted in multiple sites, the research results were announced at the annual meeting of the European Congress of Rheumatology in June. The investigators presented outcomes data on the use of a subcutaneous (SC) form of infliximab-dyyb. Currently, infliximab is only available as an intravenous (IV) infusion at the physician’s office that takes at least 2 hours. Subcutaneous infliximab was given on a biweekly basis.

subcutaneous infliximabThe researchers studied 48 patients with rheumatoid arthritis, finding that outcomes were not clinically different through 30 weeks of follow-up. Three dosages were tested, and in this small study, no ACR20 differences were reported in any subgroup receiving infliximab infusions or SC injections.

Hypersensitivity reactions did occur in one patient each receiving the lowest dose (90 mg) SC and the middle dose (120 mg). None were seen in the group receiving the highest infliximab SC dose (180 mg). Injection site reactions occurred in two patients apiece in the 90 mg and 180 mg dose cohorts. receiving subcutaneous infliximab. The formation of antidrug antibodies was detected in nine patients receiving the standard infusion, but less than half that number in each of the subcutaneous groups.

Currently, infliximab treatment requires a lengthy office visit for each infusion (every 8 wk in the maintenance phase). It is one of the key limiting factors to its use. A self-injectable formulation should result in lower administration costs, and the potential for covering the agent through the pharmacy benefit.

A phase 1, open-label trial of subcutaneous infliximab has already been conducted by Celltrion in patients with Crohn’s disease. That trial found similar outcomes between the SC and IV formulations. Another phase 1 trial is wrapping up, this one evaluating safety and pharmacokinetics in healthy volunteers. Celltrion is also sponsoring a phase 3 trial of more than 300 patients with rheumatoid arthritis. Preliminary results will not be available until December 2018.

It is not yet clear, however, what type of data the Food and Drug Administration would require for approval of a new formulation of a biosimilar. The regulatory agency may decide to treat this as it would a new route of administration for any approved product, which would focus on pharmacokinetic and pharmacology factors. Celltrion seems to be covering all of its bases.