Implications of UnitedHealthcare’s Preference of Remicade and Neulasta to Their Biosimilars

In a significant coverage move, UnitedHealthcare (UHC) has signaled that its commercial and Medicaid medical policies on infliximab and pegfilgrastim have changed direction in favor of the reference drugs.

UnitedHealthcare and biosimilars

Effective July 1, 2019, approximately 22.5 million commercial and 6 million Medicaid UHC members will not be able to access these biosimilars without trying the reference agents first (virtually eliminating biosimilar use). Both infliximab and pegfilgrastim are covered generally under the medical benefit as office-based infusions, and preferring Remicade® and Neulasta® (including OnPro®).

This move is important for a few reasons. First, it reverses UHC’s previous position, which preferred the biosimilars over the two originator products.

Second, it promotes a prior authorization practice that makes little sense—since the biosimilar and reference products are expected to work in the same way and produce similar outcomes, why would a patient who fails Remicade then be given Renflexis® instead of a different biologic medicine like adalimumab, ustekinumab, or others?

Third, it implies that both manufacturers have further reduced the net cost of these drugs to UHC and its customers, undercutting the current deals offered by the biosimilar manufacturers. If accurate, this is a positive development in that infliximab and pegfilgrastim prices are continuing to come down due to competition. It would also indicate that Amgen, maker of the pegfilgrastim originator Neulasta, is beginning to defend its prefilled syringe market more aggressively. This is significant, because Amgen had been more focused on defending the marketshare of its on-body injector (Onpro), which is dominant. Alternatively, Amgen may be bundling its filgrastim and pegfilgrastim products more effectively. Coherus and Mylan had previously announced pricing that would be one-third less than the list price of Neulasta. Coherus had specifically indicated that it would be seeking targeted deals with payers to ensure at least parity position for its prefilled syringe product Udenyca®. It did not, however, mention UHC as one of those payers.

Fourth, this move puts a further dent into the sustainability of the US biosimilar market. Obviously, preferring the originators will make access to their biosimilars considerably more expensive for patients. It can only promote greater price cuts by the competing brands and thus reduce profit margins for the biosimilar manufacturers. In the US, biosimilar makers need a little encouragement to stay in the market, as very few have had positive experiences to date (e.g., Pfizer, Boehringer Ingelheim, Momenta, Apobiologix to name a few).

No one denies the benefits of the increased competition meaning a halt to price increases and significantly lower net costs, but those benefits need to be extended across other biologic categories. Without a viable biosimilar industry, access to lower-cost biologics can only happen through price controls.

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.

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.

A Conversation With Steven G. Avey, MS, RPh

In May 2016, I interviewed Steven Avey, Vice President, Specialty Pharmacy, MedImpact, for the Center for Biosimilars. That conversation speculated on the potential for biosimilars, having only recently experienced the launch of the first biosimilar in the United States, filgrastim-sndz. At the Academy of Managed Care Pharmacy’s 2019 annual meeting last week, I sat down with Steve once again to gain his perspectives on changes in the biosimilar environment.

Biosimilars Review & Report: Congratulations on winning the Academy of Managed Care Pharmacy Foundation’s Steven G. Avey Award! This is sort of a double honor, first having the award initially named after you, and then many years later, winning it yourself!

Steve, you’re considered one of the real thought leaders in managed care pharmacy. What do you consider to be the main challenges facing your colleagues today?

Steven Avey, PharmD: Thank you. There are many real challenges today. First of all, we have the potential for drug rebates to go away. It’s clear that something is going to be done (and we don’t know what that is), and it could apply not only to Medicare Part D, but possibly Medicaid and commercial. We will need to wait and see.

Steven Avey, MS, RPh

Another challenge relates to the Administration’s emphasis on reducing list prices for drugs. This will not only influence the industry, but managed care pharmacy as well.

That challenge is part of the ongoing concern about the cost of specialty medications (and continuing price increases), and the greater call from payers for a better understanding of the value that they’re getting from these medications. Are the people who are taking specialty medications actually getting real benefit?

BR&R: In addition to payers, employer purchasers and others have been requesting a better understanding of the value of specialty medications. This has been sought for 10 years or more. Are we any closer today in getting a grip on this?

Avey: I think we are. Many PBMs are getting more involved in data management regarding these medications. The better we get at analyzing the medical and pharmacy data together, the closer we will get to understanding the value of these specialty medications.

To give you an example, a PBM today is basically reviewed and assessed on what its financial picture looks like—are you able to bend that specialty cost trend? But if you don’t know what these specialty agents are really doing for the patient population, how can you tell if covering them is the right thing to do? In order for us to know that, we have to evaluate the medical and pharmacy data together and focus on the total cost of care of that individual member. Over time, you can say that our costs are either going down or not. Then, we can ask the question, am I using the right agent or should we be using those very expensive drugs for these patients?

Given the lack of the medical and pharmacy data, we just don’t know. That’s one of my greatest frustrations.

BR&R: Let’s switch to biosimilars. Do you believe that if the rebate safe harbor is removed for Medicare, payers will also stop seeking them?

Avey: Yes. It will definitely trickle into the commercial side. I can see a day in the not too distant future where we don’t rely at all on rebates. It will be a new world focused almost solely on list price reductions.

BR&R: Will that give biosimilar manufacturers an edge?

Avey: It will be a boon for biosimilar makers! When the rebate goes away, then all that remains is the list price. That will be a huge advantage for biosimilars.

BR&R: Well, if I’m a reference biologic maker, whose R&D costs were paid off a decade ago and whose profit margin is extremely high, I can still lower my WAC price considerably to compete with the biosimilars, right?

Avey: They can, but they will have to compete with three or even five biosimilars who do not have to spend millions of dollars on advertising or promotions like the innovators do to keep their brand’s exposure and visibility high. The innovator drug maker will do everything possible to avoid losing that high market share.

Now, I haven’t seen much of this in print, but payers are angry—they’re angry at these 10% to 20% increases in costs each year from the innovator drug manufacturers. As a payer, if a biosimilar is available, why would I want to support that innovator maker, who has dramatically raised costs for the last 10 years? That gives biosimilar manufacturers the advantage: “Hey, I’m the new guy helping you to reduce costs. How about supporting me instead?” I think many payers will act on this message.

BR&R: In our conversation in April 2016, that was the gist of what you said.

Avey: And I haven’t changed my mind.

BR&R: I asked, how soon are you going to drop the AbbVie contracts (when there was some expectation that biosimilars would be available before 2020), and you said, “As soon as humanly possible.” And you weren’t the only one who said this.

Avey: Absolutely. And now the timeline has been extended to 2023. This just made us all the more angry, because this is because AbbVie filed 100 patents on Humira®, which overwhelmed what the BPCIA was intended to address. The result is that AbbVie is going to make $16 billion a year (and more each year) for 4 more years before we’ll be able to see some competition for their market.

BR&R: Genentech (Roche) is coming out with subcutaneous forms of Herceptin® and Avastin®. Will these introductions change the way you position the biosimilars for these two cancer agents, when they are finally launched?

Avey: We’ve dealt with this 15 years: It’s really no different than what we’ve seen occur with conventional agents. Consider a sustained-release form of a brand that is approved around the time the generic for the immediate-acting formulary is launched. You look at the new product and ask, what does that premium in pricing buy us? Is it a site-of-care advantage? Maybe, but does it really offset the cost of using that more expensive agent? We generally decide to cover the lower-priced (albeit it not as convenient) dosage form. With biologics, the cost differential between the new agent and the biosimilar is very large, and there is very little advantage for the new subcutaneous formulation.

BR&R: We are seeing something similar playing out right now with pegfilgrastim. Most of the market has moved to the use of Amgen’s on-body injector OnPro®, and the biosimilars are being launched using prefilled syringes. To the extent that payers are interested in eroding OnPro’s marketshare, assuming the price difference is substantial, OnPro does represent a bit more patient convenience. Some payers may be thinking this way. To the extent that this will happen may predict some similar effect for the trastuzumab and bevacizumab markets.

Avey: You have to remember that payers are receiving a lot of criticism that we’re not doing a good job of supporting the biosimilars. Quite frankly, the biosimilar drugs that have been approved up until now are really covered under the medical benefit. We have a little trickle that can be covered under the pharmacy benefit. Payers have only so much bandwidth. They know that under present conditions, a new biosimilar has to build market share from scratch. Some have said, “You know, it’s not worth the effort. We have other fish to fry. We’re not going to get too excited yet about these products.”

We have an HMO client that did an amazing job moving market share away from Neupogen® to Granix®. But they own their prescribers and they can easily analyze the combined medical-pharmacy spend. They saw a dramatic lowering of expenditures.

BR&R: Are you expecting biosimilar products for trastuzumab and bevacizumab to be managed under pharmacy?

Avey: We see those drugs under the pharmacy benefit now. Remember that those drugs have a greater utilization than the other biosimilars that have been launched to date. I do think that they will attract a lot of attention. And if the rebates do go away, that takes the market share question right off the table. The biosimilars will do quite well.

BR&R: The four-letter suffixes: The FDA recently came out with an updated guidance, saying that the agency will no longer consider adding four-letter suffixes to previously approved reference agents. However, they will continue to add suffixes to newly approved biosimilars and interchangeable agents.

Avey: Everybody is trying to figure out what’s next here. When we look at biosimilars’ pharmacokinetic information, one biosimilar is going to be somewhat different than another. I don’t think it will be an insurmountable problem, but just a headache. We’ll just have to be more in synch with our specialty pharmacies to ensure that they stock and dispense this one biosimilar with this one four-letter code.

BRE&R: Have we made any progress from an educational standpoint here? Do providers and patients still think that a product with a four-letter code is not comparable to the originator brand? What is the level of discomfort today?

Avey: I’ve watched this carefully over the last year. I don’t think there will be huge angst from the payer. The prescribers and to some degree the patients that will need more educating to make them feel more comfortable. We will need better educational materials and communications for them. The situation is really no different than when we started instituting the generic substitution laws. We heard a lot of claims that docs will never prescribe generics, patients will never take them. We had to do a lot of educating to alleviate their fears, and to help prescribers understand that these drugs work like the brands work. At the end of the day, I don’t think that this will be a long-term challenge.

A Conversation With Doug Long, IQVIA

Doug Long, Vice President of Industry Relations at IQVIA (formerly QuintilesIMS), spoke with us about some of the intracacies of the filgrastim and pegfilgrastim marketplace, and regarding improving access to biosimilars in general. 

Doug Long
Doug Long, IQVIA

BR&R: Do you think interest by manufacturers in biosimilars is gaining or waning at this time?

Doug Long: It’s somewhere in between those two. A lot of people are staying in the game to see how it plays out. Maybe discouraged most accurately describes their feelings at this time. They are discouraged, because there are 17 approved products but only 5 are available. And the uptake of those on the market is not that great, particularly compared with the uptake in Europe.

BR&R: I can see how manufacturers and payers would be discouraged right now. You’re right, in the European market, we’ve seen a great deal of uptake and significant discounting as well. So many factors affect biosimilar coverage and uptake. It may also relate to the individual biosimilar’s disparate marketplace situations.

DISTINCT MARKETS FOR BIOSIMILAR DRUGS

In the US, based on the utilization numbers seen today, do you believe the infliximab, filgrastim, or pegfilgrastim markets will best characterize how other biosimilars (e.g., Avastin® or Herceptin) will perform when available?

Long: Well, with the filgrastim molecule, you need to look at both filgrastim and pegfilgrastim, and their routes of administration (prefilled syringes and on-body injectors). Granix® and Zarxio® have the majority of the dollar share on the filgrastim side. It’s too early to tell on the pegfilgrastim side, though Amgen has a 61% share of that Neulasta® molecule with its Onpro® formulation. The addressable market for the molecule is really only the remaining 39%.

You also have to make a distinction between how much of the market is controlled by the pharmacy benefit managers compared with the hospital group purchasing organizations (GPOs) or buying groups. Most of the filgrastim and pegfilgrastim is controlled by the hospital buying groups, and that’s also going to be the case for the cancer-treating biosimilars. There’s no doubt in my mind that when Humira® or Enbrel® are available, the PBMs will embrace the biosimilars. There are just so more complexities on the hospital side of the market that it makes it more difficult for them to move towards the biosimilars.

DEEPER INTO THE FILGRASTIM/PEGFILGRASTIM SCENARIOS

BR&R: There’s an interesting situation brewing in the filgrastim market. The success of Granix and really Sandoz’s Zarxio penetrating the market has contributed significantly to the drop in total sales revenues for filgrastim sales combined. However, how much of this decrease is attributable to migration to pegfilgrastim, and Neulasta Onpro in particular?

Long: Sure, look at their revenues today. Filgrastim is at $611 million in annual sales and pegfilgrastim is at $4.3 billion. Of that $4.3 billion, Onpro accounts for 61%.

BR&R: At Coherus’ fourth-quarter earnings conference call, their CEO indicated that he thought the Onpro marketshare might be vulnerable to the pegfilgrastim biosimilar, which is available today in prefilled syringes. Obviously, that would mean selling Undenyca® at a more enticing price, below the 33% discount currently offered. Do you think that Onpro sales erosion is likely or does the formulation offer real value?

Long: That could work, but the thing about Onpro is that when you finish your chemotherapy for the week, they put the injector on you and you don’t have to go back to the doctor’s office for a pegfilgrastim injection the next day. That’s one of the reasons it is as popular as it is—it reduces hospital and doctor expenses at the end of the day, and is more convenient for the patient.

BR&R: Biosimilar manufacturers like Coherus have expressed interest in developing its own on-body injector for its biosimilar. It seems to present distinct advantages. Does that mean that the biosimilars will be relegated to fighting only for that prefilled syringe market, the remaining 39% of utilization?

Long: It’s probably too early to say. Fulphilia® has only been marketed since July, and the other one [Udenyca] was launched only recently. We’ll have to see what kind of uptake it gets. Also, we’ll have to see what happens when other players come to the market. The more drugs you have available, the more share erosion from the originator you’ll likely see. Yet that did not happen with Remicade…

BR&R: That may be more of a special situation, considering the actions taken by Janssen Biotech to prevent coverage of both Pfizer and Merck’s products.

The filgrastim/pegfilgrastim markets are also different for that reason: Amgen did not aggressively defend their market share on the prefilled syringe originator products (i.e., Neupogen® and Neulasta). Rather, they focused on getting conversions to Onpro. So the biosimilar manufacturers were not facing aggressive defensive tactics, like those employed by Janssen. 

Long: Yes, but they will defend Onpro as much as they can.

BR&R: And Amgen established Neulasta and the Onpro formulation at the same price point.

Long: It made sense. It was a good defense mechanism.

BR&R: It does force the biosimilar manufacturers to work harder to gain business.

AN UNCLEAR FUTURE

BR&R: The Administration has several initiatives that may directly or tangentially affect the biosimilar market. These include the Medicare International Pricing Index, the move to place Part B drugs into Part D (and allow step therapy and other UM tools), the reevaluation of drug rebate safe harbors, and of course, the individual components of the Biosimilar Action Plan. Do you think this will ultimately result in artificial price deflation? Would that be helpful or harmful to biosimilar makers?

Long: That’s a question that I really don’t have an answer for. Who knows what’s going to happen? People have started to make moves to reduce WAC prices, like Amgen on their PCSK9 inhibitor and Gilead on their hepatitis C treatment. Gilead created an “authorized generic” to reduce its price dramatically.

People are starting to play around with it. Maybe to get adopted, a biosimilar maker may actually have to raise their drug’s WAC price higher than the originator, and then give a larger rebate.

Biosimilar Maker Adello Biologics Bought by Pharma Research Company

The assets of biosimilar drug developer Adello Biologics were sold to Kashiv Pharma, LLC, the companies announced on January 4, 2019. The new company will now be known as Kashiv Biosciences, with its headquarters in Bridgewater, New Jersey.

Adello Biologics

Adello Biologics had been one of a handful of “pure-play” biosimilar companies, in that it was not involved with any other pharmaceutical sectors. Its two biosimilar products in most advanced development (filgrastim and pegfilgrastim) would be subject to heavy competition if approved. The acquisition by Kashiv now broadens the pipeline. In a press release, Kashiv cited “As a result of the acquisition, Kashiv BioSciences’ broad business offering includes drug delivery platforms incorporating delayed-release technology and gastric retention systems that improve the efficacy and safety of known drugs; a 505(b)(2) pipeline of seven development products targeting unmet clinical needs.” It does not appear that any of the 505(b)(2) agents are currently being evaluated for approval by the FDA.

A privately held company, it had been known as Therapeutic Proteins International since November 2016. Adello filed for Food and Drug Administration (FDA) approval for its filgrastim biosimilar in September 2017, with a decision expected in the third quarter of 2018. The delay in approval lends speculation to the possibility that FDA issued a complete response letter to the company. This filing was based on the submission of phase 1 data only. In March 2018, Amgen filed a lawsuit against Adello in New Jersey District Court, claiming patent violations and that Adello failed to follow the necessary biosimilar development protocol outlined by law.

The company’s pegfilgrastim biosimilar (TPI-120) had completed two phase 1 studies by the beginning of 2018, and it was hoped that the company would submit its FDA 351(k) application before the end of the year. Executive Vice President & Chief Business Officer Pavan Handa confirmed in an E-mail that the pegfilgrastim program “is in active development and we continue to make significant progress towards a filing. ”

Adello’s journey highlights the potential financial problems that biosimilar-focused companies may face. As a privately owned company, its capitalization was likely limited, and delays in reaching the market become even more critical for companies without other revenue-generating products. The deal with Kashiv breathes new life into the enterprise, but Kashiv, too, does not yet have an approved biosimilar product (nor approved innovative drugs) to its credit. Before the acquisition, Kashiv had focused on “applying novel technologies to improve the delivery of compounds with otherwise problematic physical and/or chemical properties” and on abuse-deterrent technologies for opioid products.

It appears to us that the purchase of Adello by Kashiv, another private company, is an effort at doubling down, to attain more immediate revenue from drug sales.

Udenyca to Launch January 3, Same WAC as Mylan’s Fulphila

Coherus Biosciences surprised many on its third-quarter earnings call late yesterday. It will rely not on a lower price than its biosimilar competitor to gain marketshare after Coherus’ Udenyca launch, but on its ability to pull through on its patient and provider services and supply chain to gain significant marketshare for its biosimilar version of Neulasta®.

This is not to imply that Coherus will not offer contracts to group purchasing organizations (GPOs), hospitals, and payers.  The company intends to do so. However, the wholesale acquisition cost (WAC) for Udenyca® will match that of Mylan’s Fulphila®—$4,175 per vial, or a 33% discount from Amgen’s reference product. Denny Lanfear, CEO of Coherus added that the company’s contracting plans “will deliver additional value to payers.”

Jim Hassard, Coherus

AWAITING HCPCS CODING

Unlike other biosimilar manufacturers, this is their first product to reach the market. Not only was manufacturing and production a priority, but company infrastructure had to be ready for launch. Although Coherus pointed out that the sales force for Coherus is fully in place, they are holding back the Udenyca launch until the Center for Medicare and Medicaid Services (CMS) designates a Q code for claims and billing purposes. Therefore, the goal is a Udenyca launch date of January 3, 2019.

Jim Hassard, Vice President for Marketing and Market Access, emphasized that “Our overall launch strategy goes beyond pricing, to reliable supply and services. We’re committed to world-class execution and salesforce effectiveness.” The company’s Coherus Complete, patient and provider service site, is operational, and this will include copay support for eligible patients. Mr. Hassard stated, “This price is attractive to payers without diminishing our value proposition. We can deliver significant savings to the health system versus Neulasta.”Coherus Biosciences

CAN UDENYCA GRAB SOME ONPRO MARKETSHARE?

One interesting statement made during the call was the expectation that Coherus will go after some of Neulasta Onpro’s share of the market. Amgen’s on-body injector accounts for about 60% of all Neulasta utilization today, “but this growth has flattened out,” Chris Thompson, Vice President of Sales, emphasized. “We’re looking at the whole market, not just prefilled syringe market,” he said. “We think we’ll be able to sell through the Onpro market,” meaning that their pricing and services will attract some of this marketshare. In fact, Coherus executives believe that biosimilars may eventually garner nearly 70% of the pegfilgrastim market.

Coherus believes that there is pent-up demand for the biosimilar in the hospital segment today, which is why GPOs may represent promising contracting opportunities. They are seeking parity positioning at the payer and pharmacy benefit manager level.

This sounds fairly reasonable. Yet the vast majority of biosimilar consultants and payers with whom I had communicated had anticipated that Coherus would launch with at least a modest WAC discount relative to Mylan’s Fulphila. On the conference call, the investment banking participants wanting information on the Udenyca launch seemed caught off guard as well.

UDENYCA REVENUE TO SUPPORT COHERUS FOR NOW

Perhaps this strategy gives Coherus ample room for contracting while retaining a respectable net cost. Mr. Thompson said, “We’ll roll out a comprehensive contracting strategy for GPOs in the next week or two. It will be competitive and designed to win.”

It may need to be. Relying on better services and perhaps even a better supply chain (albeit one that is brand new) may not be sufficiently persuasive to hospital and payer P&T Committees. And Coherus needs to generate revenue from its sole product to feed its new sales team, new product development, and hungry investors.

Coherus Gets FDA Approval for Its Pegfilgrastim Biosimilar

With the Food and Drug Administration (FDA) approval today of Coherus Bioscience’s Udenyca™ (pegfilgrastim-cbqv), the second pegfilgrastim to compete with Amgen’s Neulasta®, much attention will be now focused on the company’s November 8 earning call.

The FDA approved Udenyca on the basis of a supportive analytical similarity package, but with phase 1 data only. Over 600 healthy subjects were given the agent to test its pharmacokinetic, pharmacodynamic, and immunogenicity safety.

We should learn a great deal by the end of the week about the nature of the competition for the injectable pegfilgrastim marketplace into 2019. In the press release announcing the approval, the company said it will reveal its launch plans, including pricing, during its week’s call. On Monday, November 5, we should hear the first information about whether Mylan’s first-to-market entry, Fulphila®, has gained some traction against the injectable form of Neulasta. Mylan launched Fulphila at the end of July.

In a previous post, we discussed how Amgen’s Neulasta Onpro® patch has already captured upwards of 80% of the pegfilgrastim business. Because of the convenience of the patch formulation, it would be surprising if Onpro’s share of market eroded significantly. However, Amgen must ensure that the net cost difference between the biosimilars and Neulasta Onpro is not noteworthy. Otherwise, payers’ can be expected to try to disadvantage Onpro through step edits or greater patient cost sharing. That would take a sizable bite out of Amgen’s large slice of the $4 billion pegfilgrastim pie.

The FDA approved Udenyca for the following indication: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. It was not approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. This indication language does not differ from that for Fulphila. Neulasta has the additional indication of increasing survival in patients acutely exposed to myelosuppressive doses of radiation.

Undenyca was also approved for sale in the EU, although Coherus has not launched there, awaiting a marketing partner.

Fresenius Kabi and Celltrion Get Good News

A German manufacturer is considering its options after the successful completion of two clinical studies involving a pegfilgrastim biosimilar (MSB11455).

Fresenius Kabi, which completed its purchase of the biosimilar business from Merck KGaA in September 2017, announced its investigational biosimilar agent had proved sufficiently similar to the reference product Neulasta® in these phase 1 investigations (conducted in healthy participants). These may serve as pivotal investigations for the manufacturer, which said in its release, “Both studies are designed to enable the application for marketing authorization in the EU and US.” This may be the first indication that Fresenius Kabi seeks to be a player in the US.

Fresenius Kabi does not yet have an approved biosimilar on the European market. It hopes that MSB11455 may propel its fortunes on both sides of the Atlantic.

Food and Drug AdministrationIn its first study, the company reported that its biosimilar “met all primary pharmacokinetic endpoints, [maximum plasma concentration], and area under the curve, as well as the primary pharmacodynamic endpoints of absolute neutrophil count (ANC).” Fresenius Kabi added that there were no meaningful differences in the frequency of adverse events in these healthy volunteers. The second study focused on the biosimilar’s potential for immunogenicity, and this was also determined to be no different between the reference drug and the biosimilar. In addition, neutralizng antibodies were not found.

If Fresenius Kabi proceeds with an application for approval in either market, it will find a good deal of competition for pegfilgrastim biosimilars. In Europe, up to 5 biosimilars may be approved (2 already are). In the US, Mylan’s product is the only one to be approved, but another (Coherus Biosciences) is expecting a decision from the Food and Drug Administration (FDA) in early November. Two others (Sandoz and Apotex) are seeking US drug approval.

In other biosimilar news…The Food and Drug Administration’s Oncology Drug Advisory Committee voted unanimously (16-0) today to recommend Celltrion’s CT-P10 rituximab biosimilar for approval. If the biosimilar is approved by the FDA, it will be marketed by Teva….Mundipharma purchased European biosimilar maker Cinfa, which has a pegfilgrastim that has received a CHMP recommendation for approval in the EU.

Tidal Wave of Pegfilgrastim Biosimilars About to Hit Europe

We had mentioned the upcoming deluge of adalimumab biosimilars aiming to hit the European market in mid-October, but another biosimilar tidal wave may actually precede this.

The European Medicines Agency (EMA) has had an extremely busy week in the pegfilgrastim biosimilars arena. In addition to granting marketing authorization to Coherus Biosciences for its pegfilgrastim biosimilar, it has also approved the marketing of Pelgraz®, a pegfilgrastim produced by Accord Healthcare. In addition, the EMA’s Committee for Medicinal Products for Human Use has also recommended approval for three pegfilgrastim biosimilars—from Sandoz, Cinfa, and Mylan.

Mylan is the only drug maker with a marketed biosimilar version of pegfilgrastim in the United States. Its product Fulphila® hit the US market in early July. Coherus’ product, Udenyca™, is awaiting a November 2 decision from the Food and Drug Administration. Coherus is reportedly looking for a partner to market its pegfilgrastim biosimilar overseas, while it intends to market the product internally in the US. This means that Accord may have the first pegfilgrastim biosimilar to reach patients in the EU, though this advantage will be short lived should Mylan in particular gain approval.

In other biosimilar news…Boehringer Ingelheim announced positive results in its clinical study of Cylteza® versus Humira® in patients with moderate-to-severe plaque psoriasis. The study results were announced at the European Society of Dermatology and Venereology.

Samsung Bioepis Co., Ltd. announced that the FDA has accepted its 351(k) application for SB5, a biosimilar to adalimumab. Samsung is the fourth manufacturer seeking to enter the biosimilar market for Humira. Two have been approved (Amjevita® by Amgen and Cyltezo® by Boehringer Ingelheim) but are not yet marketed. A decision on Sandoz’s application is expected later this year.