United Kingdom to Save 75% on Annual Humira Spending

Since the October expiration of Abbvie’s EU patent, the potential Humirsavings seem to be truly mind-blowing. After implementing its contracts for adalimumab, the UK National Health Service (NHS) should save about three quarters of the $514 million (£400 million) it spends each year on this product alone.

In a fixed-budgeted system like that in the UK, the real implications of these savings become clear. According to the NHS, this additional $385 million (£300 million) will enable it to pay for 11,700 community care nurses or 19,800 treatments in patients with breast cancer.

And to earn these Humira SavingsHumira savings, the NHS does not exclude using the originator product Humira. It has signed contracts (with large price cuts) with Abbvie, as well as with biosimilar manufacturers Amgen, Biogen, Mylan and its partner Fujifilm Kyowa Kirin, and Sandoz.

Could the US see such savings on adalimumab in 5 years? Although the competition may be fierce when the brand loses patent protection in 2023, Abbvie has created a stepped-launch scenario with its licensing agreements. Rather than a jailbreak of competition, as we are seeing in the EU with patent expiration there in October 2018, the timing of the licensing agreements may limit the drop in per-unit price, at least for the first year or so.

After that time, payers will be able to choose from all biosimilar adalimumab manufacturers, which should then drive pricing down (or rebates up) considerably, resulting in long-sought lower net costs. However, this will happen only after years of price increases by Abbvie. Abbvie has not claimed, while it is drastically slashing its price in the EU, that it will be losing money. In part, that is because its US revenues on Humira will continue to be at over $10 billion a year. Furthermore, its revenues largely reflect pure profit on the manufacturing of the product today, as its research and development costs were covered 15 years ago and ongoing marketing costs are a tiny fraction of this figure.

Despite repeated protestations in the US that healthcare resources are not unlimited, our system is not based on a fixed budget. It is not disingenuous to consider savings in the terms posed by NHS. Defining the large savings in terms of other useful expenditures give people a concrete idea of how the money can be better used. The need for savings on drug expenditures is acute in this nation, and biosimilars will eventually lead the way.

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.

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.

Mylan Rethinking Its US Business Strategy?

In reporting lower earnings on its second-quarter revenues, Mylan may have surprised industry observers by offering the possibility of some changes in strategic direction. Although Mylan executives sounded hopeful notes on the company’s biosimilar portfolio, the hints CEO Heather Bresch provided may affect the marketing of the biosimilars as well as its other pharmaceutical business.

Mylan CEO
Heather Bresch

Chief Executive Officer Heather Bresch said that Mylan’s generic drug business was the main reason for the declines in overall revenues, with adjusted gross profit from US business down 6% from the previous quarter last year. Sales revenues from North America as a whole were down 22% compared with an increase of 10% for the rest of the world.

On a conference call to announce the earnings, she noted that “our efforts to serve patients in the U.S. have been shaped by the industry’s transformation there, and our results and guidance for 2018 are directly correlated with the ongoing rebasing of the US healthcare environment.”

According to Rajiv Malik, President of Mylan, “This past quarter, Mylan continued to execute on its commitment to expand access to medicine through the advancement of our complex product portfolio across our global diversified platform. For example, we launched Fulphila™, our pegfilgrastim biosimilar, in the US, and CHMP issued a positive opinion for our biosimilar of Humira in Europe.”

The Board of Directors released its own statement, however, indicating that it may take a number of actions that could dramatically change the picture (though not specified, these could include selling off assets, seeking a merger, or restructuring the organization). In a press release, the Board said, “we believe that the US public markets continue to underappreciate and undervalue the durability, differentiation and strengths of Mylan’s global diversified business, especially when compared to our peers around the globe. Therefore, while we will continue to execute on our best-in-class, long-term focused sustainable strategy, the Board has formed a strategic review committee and is actively evaluating a wide range of alternatives to unlock the true value of our one-of-a-kind platform. The Board has not set a timetable for its evaluation of alternatives and there can be no assurance that any alternative will be implemented.”

Observers will be greatly interested in how Fulphila performs in the third quarter and beyond, particularly around the deep discount offered by Mylan. This could be a considerable shot in the arm to Mylan’s US revenues or simply a ratification of its opinion that the US health system is incentivized by higher prices.

 

Mylan’s Fulphila Pegfilgrastim Biosimilar Launches at Big Discount

The first pegfilgrastim biosimilar (Fulphila™) in the US has begun marketing, and Mylan/Biocon are offering a 33% discount to the wholesale acquisition cost (WAC) of the originator product Neulasta®. The Center for Biosimilars reported a communication from Mylan confirming the action. This is a watershed moment for the pegfilgrastim category and could signal the beginning of large savings opportunities for payers and patients.

At a WAC of $4,175 per syringe, the pegfilgrastim biosimilar may be very attractive to health plans and insurers. It is also assumed that this will effectively drive down the average sales price (ASP) of the category over time. The ASP includes the WAC as well as any rebates or discounts given by the manufacturers.

The pegfilgrastim biosimilar, like the reference drug, Amgen’s Neulasta, is approved to decrease the incidence of infection as manifested by febrile neutropenia in patients receiving myelosuppressive chemotherapy.

Although patent litigation between the partners and the maker of the originator product (Amgen), Mylan/Biocon have decided to launch at risk. This means that if the District Court sides with Amgen, Mylan’s could face large financial penalties, including profits on the sales of the biosimilar.

FDA Advisory Committees on Biosimilar Applications: Mylan’s Latest Muddies the Waters Further

When the Food and Drug Administration (FDA) approved the first biosimilar pegfilgrastim (Mylan’s Fulphila™), it broke precedent in more ways than one. Not only was this the first biosimilar member of the pegfilgrastim class to be approved, but its approval did not require an FDA Advisory Committee recommendation.

The FDA has been a bit fuzzy with respect to when an FDA Advisory Committee will be necessary. In the past, however, these AdComms had been required for all first biosimilar approvals to a new reference product. This was the case for filgrastim, infliximab, etanercept, trastuzumab, bevacizumab, adalimumab, and epoetin. Second biosimilars did not always require an AdComm, most recently last September with Boehringer Ingelheim’s Cyltezo®, the second adalimumab approved by FDA.

FDA Advisory CommitteeVarious problems with the 4 pegfilgrastim biologic license applications and resubmissions have provided the FDA ample time to review data and mull the consequences of approval or rejection. This case could be an exception. A greater challenge may be upcoming though.

Not that a great deal was achieved with the biosimilar AdComms. In general, votes for recommended approvals have been unanimous or lopsided. A recommendation for approval does not always result in approval—sticky manufacturing issues have gotten in the way (e.g., for Pfizer’s Retacrit). The FDA Advisory Committee meetings does give the public and other stakeholders a chance to air their views. Generally, this has been not for or against the biosimilar being reviewed but for or against biosimilars as a whole.

In March, I raised the case of Adello Biologics, which is attempting to gain approval of its filgrastim biosimilar without any phase 2 or phase 3 clinical data. This may be the second filgrastim biosimilar approved, so the FDA can avoid an AdComm on this basis. More importantly though, this agent could be the first biosimilar approved without any patient-based clinical testing (phase 1 is usually conducted in healthy volunteers). The next FDA Blood Products AdComm is not scheduled until November 29, 2018, and we do not know if Adello’s product will be part of that discussion. With a submission date of September 2017, one would expect a decision from FDA in the third quarter of this year.

In other biosimilar news… Celltrion resubmitted its 351(k) application to the FDA for its biosimilar version of trastuzumab. The original application resulted in an April 5 complete response letter for the Celltrion/Teva team.

Mylan and Biocon Land First Pegfilgrastim Biosimilar Approval

The race to bring a pegfilgrastim biosimilar to market officially started on December 17, 2014. The checkered flag fluttered 3½ years later on June 4, 2018, with the Mylan/Biocon team winning on a slow track. The partners earned approval from the US Food and Drug Administration (FDA), becoming the first biosimilar to challenge for this $4 billion market.

Mylan will market the product in the US, and it is assumed that the product will be launched shortly,= to take advantage of their window of opportunity. The drug will be called Fulphila™, and the FDA assigned a formal name of pegfilgrastim-jmdb. The next likely competitor, Coherus, is expected to receive word from the FDA by November 2. Mylan will have the chance to quickly grab marketshare if they produce attractive deals for payers.

FDA Approval Eludes Amgen for Biosimilar Trastuzumab

Amgen will have to wait a bit longer to market its biosimilar version of trastuzumab . On Friday, June 1, the Food and Drug Administration (FDA) rejected Amgen’s 351(k) application for its Herceptin® biosimilar. biosimilar trastuzumab approvalIn a brief press release, Amgen announced receiving the complete response letter for ABP 980. In the announcement, it also said that the delay in its biosimilar trastuzumab approval should not “impact our US launch plan.” This may signal that even if it received approval, it would not market the biosimilar trastuzumab immediately.

The timing of the FDA announcement on the biosimilar trastuzumab approval contrasted with the near-simultaneous marketing authorization of this same trastuzumab biosimilar by the European Medicines Agency. The biologic will be marketed in Europe under the trade name Kanjinti™.

Mylan/Biocon’s Ogivri™ remains the only biosimilar trastuzumab approved by the FDA. It is not yet marketed, however. Separate trastuzumab biosimilars by Teva/Celltrion and Pfizer have been stalled by the FDA. Samsung Bioepis’s entry is due for an FDA approval decision in the fourth quarter of 2018.

In related biosimilar news… in September 2017, Mylan filed a 505(b)2 application for its insulin glargine agent. The manufacturing duo of Mylan and Biocon received a rejection from the FDA on June 1. The complete response letter specified issues raised by a change in manufacturing site (from one in India to a new facility in Malaysia). As reported by the Economic Times, the complete response letter was expected by Mylan and Biocon. They told the Economic Times, “Together, Mylan and Biocon are already executing on all required activities we had agreed upon with the FDA, and they are progressing according to plan,” the statement said.

Although insulins are not currently approved through the 351(k) biosimilar pathway, they are among the “transitional agents,” which by 2020 will be considered biosimilars by the FDA.

What Is the Biosimilar Pegfilgrastim Market Opportunity?

We’ve covered the contest to bring a biosimilar pegfilgrastim to market, with considerable depth. The progress and setbacks of Mylan/Biocon, Coherus Biosciences, Sandoz, and Apotex have been tracked. Other drug makers are also working on plans towards 351(k) applications for approval. Eventually—likely sooner than later—one or two will hit the market.

Biosimilar Pegfilgrastim, Neulasta®, and Onpro®

Amgen, maker of the originator product Neulasta®, disclosed in its first-quarter financial report that the total sales for the product in the US is $1.0 billion, $146 million for the rest of the world, for a total of $1.15 billion. This means a US market of approximately $4 billion for one year of sales. Amgen also noted that 62% of its first-quarter Neulasta sales are associated with its Onpro® kit. Although the major patents for pegfilgrastim have expired, Onpro is still protected by patent. Onpro does have some significant advantages in that the patient does not need to go to the doctor’s office for an injection after receiving chemotherapy. The sales figures indicate that doctors prescribe it in preference to the injectable form of pegfilgrastim.

Neulasta OnproAt a current 62% marketshare for Neulasta Onpro, the initial total slice of the pie available for biosimilars may only be $1.5 billion (not considering WAC discounts). If we assume a 20% discount, this may be closer to $1.2 billion. It may not seem logical for Amgen to make great efforts to defend its share of injectable pegfilgrastim because of its successful conversion to Onpro. Also, Onpro does have marketable advantages over the injectable form.

The list price of Neulasta is upwards of $7000 per injection, and Amgen does not charge additionally for the Onpro kit. This stance may prove an incentive to health plans and insurers to not encourage biosimilar use over Onpro.

Will Physicians Resist Moving From Onpro to a Biosimilar Pegfilgrastim Injection?

The $1.2 billion to $1.5 billion estimate also assumes that Amgen cannot convert more patients to Onpro prior to approval of a new biosimilar. That would further shrink the revenue opportunity. Physicians may also resist payer efforts and not prescribe the injectable form if they favor the Onpro kit. To the extent that payers may prefer the biosimilar (or otherwise restrict the use of a more expensive originator agent) when it becomes available, that slice of the pie could increase quite a bit. Furthermore, the picture could also change in a few years as biosimilar manufacturers develop delivery systems that gain the same advantages as Onpro.

In its earnings report, Amgen indicated the sales of Neulasta have been decreasing, by 5% from the same quarter last year. This may be the result of movement to other, less-toxic cancer chemotherapies or other treatments to prevent neutropenia and its related infections.

The Onpro market for the rest of the world may be given a boost soon, as Amgen also announced that the European Medicines Agency issued a positive opinion for the drug maker to include the Onpro Kit in its EU label.

As reported in BR&R, Coherus CEO Denny Lanfear thought the pegfilgrastim market may be split in a manner similar to that for filgrastim (i.e., 30%/30%/40% shares for 2 biosimilar makers and the originator). That may possibly mean 30% of a $1.2 billion US market (not $4 billion), if payers do not emphasize the use of the biosimilar over Onpro.