Boehringer Ingelheim Gives up the Fight, Signs AbbVie Agreement on Adalimumab

It seems that AbbVie has won the battle and the war. The last remaining holdout in the fight to bring a biosimilar adalimumab to market before 2023 has capitulated, as AbbVie announced May 14 that Boehringer Ingelheim agreed to the terms of a licensing arrangement. This agreement allows Boehringer Ingelheim to enter the marketplace July 1, 2023, getting a slight jump on some other licensees, but it effectively ends the protracted patent litigation that Boehringer hoped to win.

In an interview with BR&R, Molly Burich, Boehringer Ingelheim’s Director, Public Policy, Biosimilars and Pipeline, told us in October 2018, “We are committed to making Cyltezo® available to US patients as soon as possible and certainly before 2023.”

WHICH COMPANIES HAVE SIGNED LICENSING DEALS WITH ABBVIE?

Company/Partner Drug Name Launch Date
Amgen Amjevita* January 2023
Samsung Bioepis/Merck SB5 June 2023
Boehringer Ingelheim Cytelzo* July 2023
Mylan/Fujifilm Kyowa Kirin Biologics Hulio August 2023
Sandoz Hyrimoz* September 2023
Fresenius Kabi MSB11022 September 2023
Momenta M923 December 2023
Coherus CH-1420 December 2023
*Received FDA Approval.

However, at that time, Ms. Burich also disclosed that Cyltezo would not be commercialized in Europe; in October, the stampede of biosimilar manufacturers had just left the starting gate. In addition, Boehringer had earlier decided to drop plans to develop other biosimilars in the pipeline and focus solely on Cyltezo. That would seem to leave Boehringer out in the cold until July 2023.

In response to BR&R’s query, Susan Holz, Boehringer’s Director of Communications, Specialty Care, provided the following statement: “As we previously shared, at this point in time, our focus remains on providing patient access to our biosimilar Cyltezo in the US, and future biosimilars activities will be driven out of this market. Boehringer Ingelheim continuously evaluates our business portfolio, and we assess potential strategic partnerships to help enhance our pipeline and development capabilities. As you know, we have stopped development activities for the rest of the world, and I am not able to comment on specifics regarding our biosimilar in- or out-licensing strategy.”

Boehringer Ingelheim had reported that it is seeking the interchangeability designation for its adalimumab biosimilar. In the possible scenario where Cyltezo won its patent challenge, and gained the interchangeability designation from the FDA (note that FDA only issued its final interchangeability guidelines draft this week), the marketing potential was rosy indeed. However, suppose the FDA approves the interchangeability label for Cyltezo. It cannot leverage it until after Amgen’s and Samsung Bioepis’ adalimumab biosimilars have launched. Will it have the same advantage? That’s difficult to say. Payers will be anxious to grab immediate savings on this product, and interchangeability may not be considered such a great benefit. That is, in four years, will payers routinely switch available biosimilar agents anyway? My guess is that health plans and insurers will be leaning in that direction.

On the other hand, it will be easier to automatically switch patients in nearly every state. That lever will only be used if Boehringer gives payers a real reason to use it—a significantly better deal than the existing options. AbbVie offered huge discounts (on the order of 80% in some countries) in an effort to hang on to some marketshare once biosimilars were available in the EU. After all, why worry about interchangeability and switching when you can continue to use Humira® at a 75% discount?

Ms. Holz told BR&R, “In regards to interchangeability, this is a very important issue for many stakeholders, as it is the catalyst for automatic substitution at the pharmacy level, which in turn may help drive efficient use of biosimilars and maximize the cost-saving potential of these important medicines.” She added, “We were very pleased to see the Agency finalized interchangeability guidance that retained the appropriate balance between a high-bar to prove interchangeability and product-specific flexibility to make such a status attainable.”

In the next four years, the price of Humira will undoubtedly rise. This will mean that savings gained in 2023 will be little more than money lost to the system over the previous 48 months. As significantly, it represents tens of billions of dollars into AbbVie’s bottom line from a product that was approved in the US 17 years ago.

Apotex/Apobiologix: Success in Canada, but Are They Shelving Biosimilars in the US?

Apotex has recently made news in Canada, introducing biosimilars and obtaining marketshare there. However, the story of Apotex and its Apobiologix biosimilar subsidiary in the US is less positive.

Apobiologix

As we’ve listed in our updated table, Apotex had originally filed for approval for its pegfilgrastim biosimilar with the FDA in late 2014 and its filgrastim biosimilar in early 2015. In 2019, no announcement has been made with regard to the filing status of either biosimilar.

In April 2018, we spoke with Apobiologix executives, who told us that the company “were still in discussions with the FDA” about the path forward for its G-CSF biosimilars. Unfortunately, this statement has not changed at all on its website. If there were discussions, they didn’t go far. And so the mystery continues.

There is some support for the view that the parent company is seeking to shed the Apobiologix subsidiary, and has been actively seeking a buyer for some time. This would make sense to a degree, as any of its newly approved biosimilars would be facing a difficult crawl to US marketshare, being the third or fourth filgrastim or pegfilgrastim biosimilar to launch.  Realizing that its marketshare potential would be substantially limited, why spend the additional developmental dollars?

In April 2018, Canada had granted the company approval to market its pegfilgrastim biosimilar (Lapelga™), and in Canada’s provincial systems, it has become a dominant player. Filgrastim was approved in Canada in 2016 (and in the EU in 2014).

According to its website, Apobiologix had been developing the following products for the US market:

  • Epoetin alfa (reference drug, Epogen®), in Phase 3
  • Darbepoetin alfa (Aranesp®), in preclinical study
  • Bevacizumab (Avastin®), in Phase 1
  • Rituximab (Rituxan®), in Phase 1
  • Trastuzumab (Herceptin®), in preclinical study

Although the pipeline lists the epoetin, bevacizumab, and rituximab biosimilars in clinical trials, no mention of any of these specific investigations can be found on www.clinicaltrials.gov, under Apotex or Apobiologix as a sponsor. A request for comment from Apobiologix was not answered by the time of this publication.

If this is the case, it is less the FDA than the parent drug maker who has lost faith in their biosimilars’ potential in the US. We can ill afford fewer active players in this market.

An Eventful May Upcoming for Biosimilars

The Food and Drug Law Institute held May 2-3, in Washington, DC, offered a few nuggets of information that are well worth mentioning here and serve as a reminder of some of the important events to happen later this month.

Janet Woodcock
Janet Woodcock, Director of CDER at FDA

At the meeting, FDA’s Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research, confirmed that the long-awaited final guidance for biosimilar interchangeability will be released by the user fee goal date of May 17, 2019. This much-delayed document should close the door on requirements for obtaining the interchangeability designation, and may well allow biosimilar makers to move towards this elusive goal.

Dr. Woodcock also emphasized that interest in biosimilars from prospective manufacturers is far from dead: “As of April 2, 2019, 77 programs (for 36 different reference products) were enrolled in the Biosimilar Product Development Program to discuss development of proposed biosimilar products or interchangeable products,” she stated. Of course, this figure includes products that are not yet off-patent. Yet it is a hopeful number that implies fairly broad interest from industry players.

As part of the Biosimilar Action Plan, HHS Commissioner Alex Azar included attempts to speed drug approvals and access through the use of “skinny labels.” That refers to granting approvals to only a subset of indications held by the reference product. This draft guidance will be issued soon.

Furthermore, revised draft guidance on comparative analytical assessments are to be released by the user fee goal date of May 21, 2019. This document may bring some clarity to the potential use of a global comparator, which could obviate the need for bridging studies for an EU-licensed reference product to a US-licensed agent. We’ll have to wait and see on this one.

On May 13, 2019, a Part 15 hearing will be held on “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.” Dr. Woodcock said that FDA will be seeking input on “biosimilar and interchangeability development requirements for insulins, use with insulin pumps and over-the-counter insulins, aspects of patient experience important in evaluating proposed biosimilar, and interchangeable insulins.

Senate Bill on Patents Could Turn the Purple Book Into Something More Useful

The Biologic Patent Transparency Act (BPTA), a Senate bill introduced by Senator Susan Collins (R-ME) in March, is an independent, bipartisan attempt to address patent thickets. It does so largely by clarifying an individual biologic product’s patent situation. In achieving this, it can also create a real reason for the existence of the Purple Book.

Biologic Patent Transparency Act

Today, the Purple Book is nothing more than a listing of biologic agents, their original FDA filing dates, and whether there are any biosimilars of the originator biologic. It provides very few dates when a biologic’s exclusivity period ends. One day, it may list whether a biosimilar is interchangeable with a reference drug, but there are no designated interchangeable biosimilars today (and that seems to be the case in the near future, at least).

Under the Senate BPTA proposal, the originator manufacturer must disclose all relevant patents to the Secretary of Health and Human Services. It states that “…a ‘patent required to be disclosed’ is any patent for which the holder of a biological product license approved under subsection [351](a) or (k), or a biological product application approved under section 505 of the Federal Food, Drug, and Cosmetic Act and deemed to be a license for a biological product under this section on March 23, 2020, believes a claim of patent infringement could reasonably be asserted by the holder, or by a patent owner that has granted an exclusive license to the holder with respect to the biological product that is the subject of such license…” We assume that the patent lists will be provided via the Purple Book, which is supposed to be a reference for prospective biosimilar manufacturers.

The BPTA strives to make the patents held by a manufacturer as transparent as possible. It would require drug makers to list exclusivity periods or any exclusivity extensions received, information related to interchangeability or biosimilarity of a product, approved indications, and mandates updates every 30 days. Of course, this language does not prohibit, restrict, or redress any existing patents. Any changes in the patent law is not the addressed in this proposal.

The seven bill cosponsors (as of May 2, 2019) include a group as diverse as Tim Kaine (D-VA) to Rand Paul (R-KY).

In other biosimilar news…Sandoz announced a partnership with Taiwan-based EirGenix to commercialize the latter’s investigational trastuzumab biosimilar. This agent is currently in phase III trials. Under terms of the agreement, Sandoz will market the agent globally, except for China and Taiwan.

Second Etanercept Biosimilar Receives FDA Approval

Samsung Bioepis scored another biosimilar approval in the US, as the Food and Drug Administration gave its nod to etanercept-ykro on April 25, 2019. Formerly known as SB4, Samsung Bioepis dubbed this agent Eticovo™. It is the second
Enbrel® biosimilar to to receive US approval.
 
This approval covered all of the reference product’s autoimmune indications, including ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, and rheumatoid arthritis. Clinical studies were performed in patients with moderate-to-severe rheumatoid arthritis, finding that in combination with methotrexate, Eticovo achieved ACR20 scores that were equivalent to that of Enbrel by week 24 (78.1% vs. 80.3%, respectively). Safety and immunogenicity were also comparable with those of the reference agent.

Eticovo has been approved in the EU and Canada, in addition to other parts of the world, under the brand names Benepali and Brenzys. Samsung Bioepis has not announced a launch date in the US for its biosimilar, and this can be delayed for quite some time. Sandoz’s Erelzi® was approved in 2016, but has not yet reached the market because of patent litigation. Amgen, which manufacturers Enbrel, believes its patents extend effectively into 2028, which would provide for nearly 30 years of product exclusivity.


Both Coherus and Lupin have investigational etanercept biosimilars that are in phase 3 trials. Neither has publicly filed for FDA approval to date.

Managed Care Pharmacists Survey: We’re on Board With Biosimilars, and Maybe Even Switching

Few suspected that payers were doubters of the clinical value of biosimilar agents, and as the first biosimilars were approved (2015-2016) managed care medical and pharmacy executives were somewhat reluctant to embrace them. However, within the past couple of years, managed care pharmacists told me these concerns were dissipating rapidly. (See the recent interview with Steven Avey as an example.)

A new survey on biosimilars released by the Academy of Managed Care Pharmacy (AMCP) confirmed that managed care pharmacists are on-board with biosimilar safety, efficacy, and the potential for switching. Conducted in October 2018, this survey offers solid evidence of the most recent thinking by pharmacy professionals on biosimilar access and promise.

Investigators from the Academy, PRIME Education, and the University of Pennsylvania analyzed the first 300 responses to their broad solicitation of AMCP members and associated professionals. Thirty-eight percent worked within a health plan or insurer setting, 22% in a pharmacy benefit management organization, and 40% in a specialty pharmacy.

The researchers stated, “84% agreed or strongly agreed that FDA-approved biosimilars are safe and effective for patients who switch from a reference biologic.” Although this does not specifically endorse switching to biosimilars from reference products, it does imply that the payers have no problem with the concept. They were still a bit wary of extrapolation of indications, however. A slight majority (54%) agreed or strongly agreed that extrapolation of indications for biosimilars was safe and effective.

The surveyed payers were asked to select the most effective strategies for increasing biosimilar utilization (i.e., overcoming barriers to biosimilar use). The responses rated the following strategies “extremely likely to be effective”:

  1. Clear FDA guidance for substituting reference biologics with lower-cost biosimilars that meet requirements for interchangeability (54%)
  2. Expanded Medicare and Medicaid policies that promote biosimilar use (41%)
  3. Educational programs for prescribers focusing on evidence from studies in which patients switched from reference biologics to biosimilars (39%)
  4. Formulary policies that promote biosimilar use for treatment-naive patients (39%)
  5. Educational programs for prescribers focusing on real-world evidence from postmarketing studies on biosimilars, including European studies (34%)
  6. Reduced cost sharing for patients using biosimilars (34%)
  7. Incentivizing providers by adjusting fee schedules for biosimilars (34%)

It should be noted that of the 16 potential strategies presented, only 2 (see below) did not garner more than 50% of respondents believing that they were at least “likely” to be effective.

In contrast, the strategies least likely to be effective were:

  1. Requiring therapeutic drug monitoring for patients who switch to biosimilars to address concerns about immunogenicity (28%)
  2. Incentivizing providers by using quotas for prescribing biosimilars to treatment-naïve patients (28%)
  3. Educational programs for prescribers focusing on streamlined billing, coding, and reimbursement processes for biosimilars (12%)
  4. Laws that promote greater public transparency on pricing of biosimilars and reference biologics (11%)

This survey does demonstrate that pharmacists’ comfort levels with biosimilars are fairly high. At the time of the study, it is likely that they had significant experience with only filgrastim and infliximab biosimilars (based on launch dates of the other approved agents, including epoetin and pegfilgrastim).

Challenges Extremely Difficult Difficult or Extremely Difficult
Concerns about biosimilar safety and efficacy among prescribers 16% 61%
Pricing and contracting issues 22% 57%
State laws for substitution and interchangeability 17% 53%
Concerns about biosimilar safety and efficacy among patients 13% 49%
Formulary management issues 8% 35%
Concerns about biosimilar safety and effiacy among payers 7% 23%
Data adapted from
https://www.jmcp.org/doi/full/10.18553/jmcp.2019.18412 .

In terms of these pharmacists’ opinions as to the most challenging barriers to biosimilar adoption, they rated as “extremely difficult”: pricing and contracting issues (22%), state substitution and interchangeability laws (17%), and prescriber concerns about efficacy and safety of biosimilars (16%).

When asked what biosimilar manufacturers can do, their responses emphasized pricing: Use contracting “to overcome the current [biologic reference] products’ substantial rebated dollars” and “come to market with more aggressive discounts off [average wholesale price].”

A Quick Look Back: Why We Misread the Signs

In the biosimilars arena, at least in the US, history seems to be truncated. Policy changes occur in rapid fire succession these days, and access scenarios don’t evolve—they just happen or they don’t! Along this brief journey, I’ve taken the opportunity to focus on some of the sign posts that were exceedingly poor maps for navigating the future.

One of the first blogs I wrote for The Center for Biosimilars in early 2016, involved a defeat for Amgen in its patent litigation with AbbVie regarding Humira®. No one was sure what the implications of this decision would be. Amgen was on the road to gaining approval of the first biosimilar adalimumab. The payer and investment community sensed momentum building towards the imminent takedown of the number 1 biologic in terms of sales. I referenced 2016 Humira revenue estimates of $14 billion for AbbVie, and mentioned two other prospective biosimilar makers—Baxalta and Momenta—being hot on Amgen’s heels.

In that same article, many in the investment community was under the belief that a US marketed adalimumab biosimilar would be available by 2020. Instead, January 2023 is looking more inevitable. I wrote, “The investment community believes that Amgen will come out on top; they believe that AbbVie will have $6 billion—not $18 billion—in Humira sales by 2020.”

I’m not sure that I could have been more wrong in my assumptions or sentiments, thinking that AbbVie’s maze of 70 patents (at the time) could be severely damaged at that time by the process to challenge patents. This may happen today through Boehringer’s efforts, but I wouldn’t count on it. The other major players don’t have the stomach for fighting this battle.

In 2017, Baxalta and Momenta have dropped out of the biosimilar contention for Humira’s marketshare, replaced by Sandoz, Boehringer, Coherus, Samsung Bioepis, and perhaps others. Baxalta and Momenta , one being taken over by Shire and the other facing financial realities.

Unfortunately, it will take a miracle, in the form of a Boehringer victory or even less likely, adoption of Dr. Peter Bach’s biologic pricing proposal, to get adalimumab to the payer market. The fact that the proposal that Dr. Bach and his colleagues at Memorial Sloan Kettering laid out received as much attention as it did tells quite a bit about our serious frustration today with access to biosimilar savings.

Of course, very few actions taken by the current Administration have yet to be implemented. These are intended to bolster the biosimilar industry and move from promised to actual savings. However, the signs are telling me that we’re not in an evolutionary phase of biosimilar development–an extinction event may be around the corner.

New Proposal: Forget Biosimilars, Move to Fixed Price Formulas

Claiming that US savings would accrue from $200 billion to $300 billion within 5 years, a group of authors published in a Health Affairs blog a different concept for controlling the cost of biologic agents. They believe that biosimilars will never gain the savings intended by the Biologics Price Competition and Innovation Act (BPCIA). Savings of more than $87 billion for Medicare and Medicaid, they believe, could be a strong inducement.

ADDRESSING BIOLOGICS AS A NATURAL MONOPOLY

Emphasizing that today’s biologics are a form of a “natural monopoly,” biosimilar manufacturers will be generally disincentivized to crack the market. The authors from Memorial Sloan Kettering Cancer Center and Massachusetts Institute of Technology explained that a natural monopoly is the result of a market where the barriers to entry are too high to encourage significant competition. The current biologic market exclusivity of 12 years, the cost to develop a biosimilar (relative to that for a generic agent), patent issues, and the barriers to substitutability have collectively limited the number of drug makers willing to enter the competition today. This natural monopoly has thus resulted in the marketing of only eight biosimilars in just four drug classes since 2012.

Addressing this issue requires a much more aggressive regulatory approach, they believe. After loss of market exclusivity, the price of biologic products should be subject to a formula that drops the price commensurate with the actual cost of maintaining the supply chain. They write, “The lowered price should equal the costs of production (including facility repair and replacement) and market distribution, plus an appropriate profit.”

Although the development of the formula can vary, they emphasize that transparency is the key element. “What is critical is that the formula be clear; be relatively easy to determine and audit; protect payers from prices substantially above the economic marginal production cost; and protect manufacturers from excessively low prices resulting from the government regulator exerting monopsony buying power.” The entity deciding on the lower price must also be a completely independent body, without connection to the manufacturers or the purchasers.

A REGULATORY APPROACH TO BIOLOGIC COSTS

This approach would parallel how Medicare pays for hospital services; profit margins are not set by the manufacturers on drugs for which market exclusivity has expired. The assumption is that these drug makers will have long ago earned several multiples of the research and development cost, and can produce these agents at a profit for 70% to 90% less than current pricing.

This regulatory proposal has a couple of interesting positive features. First, it decouples patent issues from access to far lower drug costs (an essential, failed objective of the BPCIA). Second, it eliminates any discussion of rebates and rebate traps. Third, it removes any question of prescriber/patient discomfort with the use of biosimilars.

POTENTIAL FOR DRUG SHORTAGES

However, it does not answer the longer-term concerns: What happens when the manufacturer of etanercept, for example, decides that he or she does not want to spend their opportunity cost on producing a drug that produces now relatively low profits? That manufacturer will either stop producing (i.e., there will not be any etanercept available because there are also no biosimilar manufacturers of it) or sell the product to another drug maker, which may then have to essentially be regulated as an interchangeable biosimilar maker. That might even be an opportunity for EU biosimilar makers to obtain US marketshare.

Furthermore, what would happen to the biosimilar makers who have already exposed themselves to very high development costs and financial risk? For those currently marketing their products, the target pricing ranges are certainly well below the net prices they offer today. Are their interests in the specific biosimilars “bought off” by the government or reference biologic makers? The authors believe that this will need to be the case, and they set aside up to $20 billion of their $200–$300 billion savings for this purpose.

POLITICALLY UNREALISTIC OR ECONOMIC REALISM?

The reference drug manufacturers would strongly oppose this proposal, whereas the payers, providers, and patients will appreciate the price savings. It would be a bloody battle indeed, exposing biologic makers to widespread price controls.

True, the attrition in the biosimilar space is already high, and the regulation of biosimilars in different countries has not resulted in consistent outcomes. For example, several agents are approved for use in Europe but have gained little more than rejection letters in the US.

The need for such a proposal is further evidence that few are satisfied with access to biosimilars in the US and the price reductions that have been seen to date. The authors’ proposal offers a measure of “pricing justice” for those who are greatly frustrated with the games that have been played by an industry bent on serving their shareholders by retaining maximum profit margins until the bitter end. Yet it does have the potential to result in new drug shortages, and wipe out the biosimilar industry as we know it in the US.

Is this a sledgehammer approach? Absolutely. However, if the overall biosimilar situation does not improve rapidly in the US, this will likely not be the only proposal that moves towards a regulatory solution and away from competitive markets.

Senate Hearings on Drug Pricing: PBMs Pass Blame Back to Drug Makers

If you thought that the Senate hearings on pharmaceutical rebates and pricing was going to help clarify what might be the best avenue for the administration to promote biosimilar access, well, you should have known better. With enough finger pointing to go around, the pharmacy benefit managers and health plans represented at these hearings passed the ball about as well as the Harlem Globetrotters during their pregame routines. It was entertaining but not very elucidating.

Senate hearings on pharmaceutical rebates

One interesting view expressed by Steve Miller, MD, former CMO of Express Scripts and now Executive Vice President and Chief Clinical Officer for the PBM’s new parent Cigna, said that the problem was that marketing exclusivity was too long for the reference biologics. “One of the biggest problems facing the industry is the lack of biosimilars that have come to the marketplace,” he pointed out, placing the blame on the overwhelming patent issues. 

The hearing held on April 9 was chaired by Senator Chuck Grassley (R-IA) and co-led by Senator Ron Wyden (D-OR). Senator Wyden said, “This morning the committee is going to be looking at one of the most confounding gnarled riddles in American health care today…whether pharmacy benefit managers bring any value to the taxpayers is a mystery.”

At a previous hearing in February at which the pharmaceutical companies provided their side of the story, the drug makers pointed to the PBMs and the need for rebates, alleging that they failed to pass through the contracted discounts to patients.

On the other hand, the PBMs blamed the pharmaceutical companies for the high list prices and limited discounts, which require rebating tactics to gain an equitable net price. In its defense, CVS Health claimed that its ability to obtain significant rebates is “a powerful tool to offset” the WAC prices set by drug makers. In response to attacks on the confidentiality of rebating deals, which benefit plans and PBMs rather than patients, they responded that these negotiations do not contribute to higher drug costs. Instead, they help secure the deal-making power of the plan or PBM.

The PBMs did argue a strong case against drug licensing and pay-for-delay deals, which extend beyond generic drugs into the biosimilar space (e.g., AbbVie on Humira). The health plan representatives also emphasized once again that stripping away the rebates would likely result in higher premiums.

One would not call the hearings “clarifying” in any respect. However, it did provide the companies a more public forum to state their positions with regard to the rebate issue and as to the value of their negotiations to the health system in general.

Sandoz Resubmits Its Pegfilgrastim Biosimilar Application

Sandoz may be chomping at the bit to market its long-delayed pegfilgrastim biosimilar. First rejected by the Food and Drug Administration (FDA) in 2016, the manufacturer of Zarxio® (filgrastim) has completed its 351(k) biosimilar resubmission for its pegylated filgrastim agent.

The FDA’s complete response letter to Sandoz required new pharmacokinetic and pharmacodynamics data, which Sandoz has provided. According to Sandoz’s press release, “The resubmission includes new data from a pivotal pharmacokinetics (PK) and pharmacodynamics (PD) study. This was a single-dose, three-period cross-over study comparing Sandoz pegfilgrastim with US-sourced reference pegfilgrastim; Sandoz pegfilgrastim with EU-sourced reference pegfilgrastim; and US with EU-sourced reference pegfilgrastim.” Branded Ziextenzo™, this agent was approved in Europe and launched in November 2018.

Sandoz was hoping that its pegfilgrastim biosimilar would be first to market before its 2016 set back. Several other prospective pegfilgrastim biosimilar makers also received rejections from the FDA, including Mylan/Biocon’s Fulphila® and Coherus Biosciences’ Udenyca®, both of which are now marketed. If approved, Sandoz would be (at best) third to market. However, of the competitors, Sandoz is the only manufacturer that can boast both a filgrastim and pegfilgrastim biosimilar. Of course, Amgen produces both Neupogen® and Neulasta®, the respective reference products.

A FDA decision date has not yet been announced; a decision in the late third quarter of 2019 would be a reasonable expectation.

Besides Zarxio, Sandoz already has received approval for two other biosimilars (Hyrimoz®, a biosimilar of trastuzumab, and Erelzi®, a biosimliar of etanercept, but these two have not yet been launched because of outstanding patent litigation or settlements. Despite having received approval in the EU for its biosimilar of Rituxan®, Sandoz decided not to press for US approval after receiving a complete response letter from the FDA about a year ago.