|Company/Partner||Drug Name||Launch Date|
|Samsung Bioepis/Merck||SB5||June 2023|
|Mylan/Fujifilm Kyowa Kirin Biologics||Hulio||August 2023|
|Fresenius Kabi||MSB11022||September 2023|
|*Received FDA Approval.|
Since the October expiration of Abbvie’s EU patent, the potential Humira savings 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 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.
Just a few short weeks ago, Abbvie announced that it intended to rely on discounts as deep as 80% in parts of the EU to retain Humira® marketshare. One bellweather EU member country has signaled that it is signing tenders with other biosimilar adalimumab manufacturers.
The Center for Biosimilars reported an Email exchange with the Danish national tendering authority Amgros, which manages the country’s bidding system. Amgros confirmed that Abbvie did not provide the best bid for two tenders for adalimumab (covering January to March 2019 and covering April to December 2019). Five companies (including Abbvie) competed for the national tenders. Although Abbvie did not rank best for pricing, agreements were signed with all five companies.
According to the report, a spokesperson for Amgro said, “In both tenders for adalimumab 40 mg, we have entered into agreements with 5 companies—the agreements are ranked according to price. In both tenders, we have signed an agreement with Abbvie for Humira—but Humira does not have the lowest price (ie, is not the winner with the highest ranking).”
The importance of this action may extend beyond Denmark, as several European countries utilize others’ pricing decisions as a benchmark for their own. For example, the price for adalimumab in Bulgaria by policy cannot exceed that in 17 other EU countries.
We previously reported that Momenta Pharmaceuticals reevaluated its biopharmaceutical strategy going forward, deciding to move forward only with its investigational adalimumab and aflibercept biosimilars. Yesterday, Momenta announced that it has joined the long queue of pharmaceutical manufacturers signing a biosimilar licensing deal with Abbvie, which will allow commercialization of M923, its biosimilar to Humira, should it obtain regulatory approval. Momenta’s licensing deal is the fifth one signed by prospective biosimilar marketers in the US.
This agreement was pretty much a no-brainer for Momenta. The company did not have the stomach for attempting either an extended patent fight or an at-risk launch. However, the biosimilar licensing agreement only allows Momenta to market its adalimumab biosimilar in the US after December 2023, which will make it the fifth Humira biosimilar that will launch under the licensing agreements (Table). The main patents for Humira have expired in Europe, and these agreements have generally allowed the European launches to occur as of October 16 of this year.
Of the manufacturers signing biosimilar licensing deals with Abbvie , only Amgen and Sandoz have earned FDA approval for Amjevita® and Hyrimoz®, respectively. And Boehringer Ingelheim is still duking out patent litigation with Abbvie in the courts over its approved biosimilar agent Cytelzo®, for which it hopes to receive an interchangeability designation. The second through fifth agents entering the fight will be likely pounding away at subsequently smaller slices of revenue.
Perhaps the most frustrating part is that Abbvie is running a lucrative game; it will collect royalties from all of these manufacturers in 2023 and beyond, which will help offset declining marketshare from its biggest revenue contributor.
In Abbvie’s Web: Who Has Signed Licensing Agreements for Biosimilar Adalimumab?
Mylan/Fujifilm Kyowa Kirin Biologics
|*Received FDA Approval.|
Note: This post was revised and corrected, November 8, 2018.
The Food and Drug Administration (FDA) announced yesterday the approval of adalimumab-adaz from Sandoz. The new agent, dubbed Hyrimoz™, will not be launched in the US until 2023. The approval of Hyrimoz is the third for Sandoz (but only one, Zarxio®, is available for prescription in the US).
The FDA approval of adalimumab-adaz covered several indications, including adult Crohn’s disease, ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. The drug’s approval was based partly on the findings of a phase 3 clinical trial in patients with chronic plaque psoriasis, in which the biosimilar was found to be noninferior to the originator product Humira® in terms of efficacy (i.e., PASI 75 score) and safety.
Hyrimoz is the third approved adalimumab biosimilar, none of which have been marketed due to patent litigation. Abbvie has signed licensing agreements with Amgen and Samsung Bioepis to delay US launches.
HUMIRA PRICE DISCOUNT IN THE EU
This biosimilar is being marketed in the EU, competing with several others for the Humira marketshare overseas. However, signs of real competition are heating up in Europe, as Abbvie has offered a Humira price discount of as much as 80%.
According to an article published in Fierce Pharma, Abbvie is hoping to squash the biosimilar competition and prevent it from gaining valuable European experience ahead of US launches in 2023. The article cited a report by Bernstein analyst Ronny Gal, indicating that even at an 80% discount, Humira will still be profitable for Abbvie. “The objective is to defend the US market by denying the biosimilars in-market experience [in Europe] and then arguing the Europeans ‘chose’ Humira over the biosimilars for quality reasons beyond price,” according to Gal’s report.
On the other hand, this puts the biosimilar makers in a tight spot on the continent. They need to earn back their R&D costs and may be unwilling to face an immediate low-profit reality. Revenues within the EU for Humira are $4 billion. Even if it offered tenders of 80% for every member country (and they were accepted), revenues would still be in the range of $800 million. This would drastically reduce the size of the revenue slices for the European biosimilar competitors. It could be possible that some may drop out of the market, at least until the time of the US launches.
The Centers for Medicare and Medicaid Services (CMS) has decided drugs covered under Medicare part B may be subject to step therapy, if so desired by Medicare Advantage plans. UnitedHealthcare has become the first to publicly implement step therapy policies for these drugs. However, biosimilar step therapy is not the typical utilization management tool that industry executives are used to seeing.
Traditional step therapy or step edits for prior authorization policies are typically used to require the use of an effective, low-cost drug class before trying a more-expensive treatment. For example, a plan might have a step in place before a patient can receive Humira®, such as requiring documented failure on other disease-modifying anti-rheumatic drugs, like azathioprine or methotrexate. This makes very good sense when supported by practice guidelines or treatment pathways, based on solid supportive evidence.
For biosimilar manufacturers, the perspective on the revised CMS policy, seems to imply trying the biosimilar before receiving the branded originator product. This biosimilar step therapy would make very little sense. A doctor would not be practicing evidence-based medicine if he or she prescribed Remicade® to a patient after failure of Renflexis®. There is no evidence to show that the biosimilar will work in a patient who did not receive adequate clinical benefit from the reference product (and vice versa). Similarly, there is no information to show that a patient who has an adverse effect while taking Remicade will not have that adverse effect after injecting with Renflexis (or vice versa). In other words, after failing one, a new mechanism of action should be tried, not a product with a very similar structure. This may be a different argument, if a subcutaneous form of infliximab was introduced, and this might be reason to step the infusible form through this drug.
In United’s announcement, they are clearly seeking to increase biosimilar utilization, as designated preferred part B agents, at the expense of Remicade use, the nonpreferred agent. Therefore, it may make more sense that new patients will have to use a biosimilar before being prescribed the reference product. Step therapy in this case is almost an aside.
Ironically, the Department of Health and Human Services has also expressed its desire to move part B agents like self-administered injectables to part D. This may not apply to infliximab, as it is given as an in-office infusion. Should this be the case, plans will have many pharmacy tools at their disposal beyond biosimilar step therapy.
In other biosimilar news…Fresenius Kabi has signed an agreement with Abbvie to delay its adalimumab biosimilar market entry in the US until 2023. The manufacturer is currently trying to secure European approval for the product. A 351(k) application has not yet been filed by Fresenius in the US.
When Pfizer first announced its lawsuit against Janssen’s parent Johnson & Johnson in September 2017, it pointed to exclusionary contracting, “anticompetitive” behavior of Remicade®’s maker as the reason for its very limited market access.
The lawsuit claimed that Janssen has withheld or threatened to withhold rebates if payers do not keep Remicade in an exclusive preferred position. The degree to which health plans knuckled under to these demands may only be inferred from the 3% marketshare Pfizer’s Inflectra® now holds. For these drugs, which are still typically covered under the medical benefit, “nonpreferred positioning” usually means no coverage. For drugs covered under the pharmacy benefit, this is not the case.
In August, the Eastern Court of Pennsylvania ruled against J&J in its request that the lawsuit be dismissed. While discovery in the case may be ongoing, we could not find mention of a resolution date for the suit.
For the sake of argument, let’s say that the Eastern Court of Pennsylvania rules in favor of Janssen. In other words, exclusionary contracting was not an anticompetitive behavior. That means the status quo is intact, but some factors may affect this situation going forward. These include the Center for Medicare and Medicaid Services’ desire to move part B drugs (the medical benefit) to part D (the pharmacy benefit) for Medicare beneficiaries.
The scrutiny on rebate contracting coming from several sectors, and lack of transparency, may also independently influence future use of these pharmaceutical company tactics. I helped conduct a market research project recently on a nonspecialty drug. As part of these interviews, we were asked by the client to inquire about the range of rebates they were receiving from competitor manufacturers. Their responses were requested as a range (e.g., 20% to 30%), not specific contract details, and we had no intention of providing reports of individual payer deals, only anonymous, aggregate information. We expected little to no response to that query, and that is exactly what we received.
Let’s discuss the other potential outcome, in which the Court rules in favor of Pfizer. That implies that this exclusionary contracting practice is indeed anticompetitive. If this is the case, we may be on a very slippery slope. What is the difference between payers and pharma companies engaging in a “1 of 1” contract when there are multiple potential products and a “1 of 2” contract? In both cases, drug makers are committing payers to anticompetitive behavior (as perhaps defined by the Court’s new precedent).
The preferred drug tier (whether preferred generics, preferred brands or whatever) is supposed to be for products with proven clinical, patient care, or economic advantages. Truthfully, payers rarely place medications in the preferred tier for reasons other than net costs or rebate contracting, which is based on marketshare.
Now add in the potential effects of the Administration’s desired shift to part D, where pharmacy benefit rules can be applied. That exposes injectable products that were shielded under Medicare part B to commonly applied formulary placement practices.
To be complete, Janssen’s strategy was not solely based on Remicade. It may be found to have bundled Remicade with other agents in deals to exclude Pfizer’s products. The Court may also react specifically to Janssen’s contract stipulation that threatens to withhold rebates connected to future use of the product, to increase its leverage.
However, if the Court determines that 1 of 1 or exclusionary contracting with rebates are the root of the anticompetitive behavior, why should 1 of 2 or even 1 of 3 contracts in a drug category with 5 similar agents be less so? This is the slippery slope that could undo rebate contracting, and push us towards a system that more resembles a competitive bidding process like in Europe. Alternatively, it could accelerate the move towards outcomes- and value-based contracting. The result could be a system-wide revamping of the drug formulary and the pharmacy–drug maker relationship.
In other biosimilar news…Sandoz has signed a licensing agreement with Abbvie, allowing it to market its biosimilar version of Humira in 2023. The agreement, as with Abbvie’s settlements with other biosimilar makers, halts all patent litigation with Sandoz in exchange for a licensing royalty paid to Abbvie.
A recent Twitter conversation between a blogging colleague of mine and a German advocate of precision medicine propelled this post: What is the real benefit of biosimilars? Does biosimilar development detract from efforts to produce innovative medicines? Is the main societal benefit biosimilar cost savings?
Biosimilar Development Is Separate From Innovation Development
The main reason that the Biologics and Biosimilars Price Competition and Innovation Act (BPCIA) was signed into legislation was related to cost containment. For biologics, there was no pathway for the evaluation and approval for lower-cost copies in the US health system, akin to the generic-brand name dynamic for conventional drugs. Adding competition has been the first and only point. The specialty drug trend had been rising rapidly, and the long-term estimates were frightening: Costs associated with specialty drugs like biologics threaten to eat 48% of the total drug spending pie in the United States by 2020.
Two factors were responsible. The first, increasing specialty drug utilization, has been especially difficult to address. The pipeline is congested with biologics. Medical societies are increasingly incorporating biologics into their guidelines and clinical pathways. Prescribers have grown more comfortable with these agents, and payers have limited tools at their disposal to put the brakes on their use.
The second, price increases, are well known and publicized. Without competition, drug companies tend to test what the market will bear, and to this point, they have borne quite a bit. Unlike in Europe, where the tender system of pharmaceutical purchasing has resulted in better cost containment, the US payers have been accustomed to stomaching large price increases through increased use of rebate contracts with price guarantees. But the overall costs continue to rise, as contracts expire and new ones are drawn up. Thus, the list prices for drugs like Enbrel® and Humira® have skyrocketed, with Humira’s more than doubling in a few years.
There is no evidence to say that biosimilar manufacturers would have engaged in the development of innovative new agents had they not devoted resources to this area. Indeed, pure-play biosimilar makers, like Coherus or Adello, were only introduced to produce biosimilars. Other makers, such as Samsung Bioepis, are joint ventures of existing manufacturers to do the same. Biogen recently raised its stake in Samsung Bioepis to nearly 50% of the company’s shares. This could be construed as a case of an originator company pouring $700 million into a biosimilar manufacturer, which could be using that money directly for other purposes. Finally, firms like Apotex, Mylan, Sandoz, and Hospira (now part of Pfizer) are heavily involved in generic drug manufacturing. Biosimilar development was a natural extension for them. Even big pharma players, such as Amgen, Merck, and Pfizer, are more commonly engaged in biosimilar marketing partnerships rather than purely R&D efforts (e.g., Amgen/Allergan, Merck/Samsung Bioepis, Pfizer/Celltrion).
One can also make an argument that pharmaceutical innovation is more evident at the drug discovery level. These days, big pharma seems less interested in pursuing drug discovery than in purchasing it.
The Societal Benefits of Biosimilars
The EMA and FDA biosimilar pathways were created to introduce competition that would lower drug costs. This in turn would make innovative biologic therapy available to more patients. Biosimilar cost savings could drive greater access to important drug technologies.
With the EU’s longer and more extensive experience with biosimilar medications, costs have indeed been saved. Although this has varied by country, it is undeniable.
In the US, with very limited economic experience with biosimilars (filgrastim and infliximab), savings figures are more theoretical than real. Although the infusion of a biosimilar into the new market may reduce wholesale acquisition price of the reference drug a bit, it will have a greater effect on net pricing, after rebates. And, of more immediate importance, the new biosimilar has the potential to halt further price increases for the originator product. This aspect of biosimilars cost savings cannot be overemphasized. Between the first adalimumab biosimilar approval and the initial availability of these products in 2023, the list price of Humira can increase upwards of 40% (or more, if Abbvie veers from its pledge to limit price increases). The initial price of the first adalimumab biosimilar will thus be much higher than if it was launched last year. On the other hand, adalimumab biosimilars will launch in the EU in October of this year, which should effectively lower cost products and limit their EU members’ exposure to future Humira price increases.
Biosimilar cost savings can have real benefits in terms of improved access. Payers’ incentives to use biosimilars (if they are motivated to implement them) can result in lower patient cost sharing. For example, a fourth-tier biologic may be subject to a 20% cost share, whereas a third-tier biosimilar may carry a flat copay of $100. This can make a difference in terms of therapeutic choices available to patients.
In conclusion, the German correspondent is only partly right. Biosimilars are not innovative. They are highly complex, cost-control medications. Do they detract the focus of manufacturers from new innovative products? There’s no evidence of this. However, we are beginning to see limited evidence in the US of the societal benefits, namely cost savings, they can bring.
Momenta seems to be in final preparations for its first 351(k) filing to the Food and Drug Administration (FDA). In its recent investor conference, the company disclosed that it is ready to send M923, its adalimumab biosimilar, to the agency for approval.
Despite this promising news, Momenta is facing strong headwinds. Even if it gains approval, Momenta expects that the US launch of the adalimumab biosimilar will not occur until 2023, owing to pending patent issues with Abbvie’s Humira®. The company does not yet have a marketing partner for this agent, though there appears to be plenty of time.
In addition, Momenta received a setback in November 2017 on another looming biosimilar candidate, when its biosimilar version of abatacept failed its phase 1 trial. Apparently, its M834 produced pharmacokinetic results that differed from the originator Orencia® in this early clinical study. Momenta is still studying the data and trying to come to grips with the surprising findings.
The company is also set to begin “pivotal” clinical trials on its other drug candidate M710, a biosimilar to aflibercept. The originator product is Eylea®, and it is indicated to treat wet age-related macular degeneration.
Momenta’s partnership with Mylan is moving forward with preclinical work on four other nonspecified biosimilars, according to the company. But all of this development costs money, and Momenta has acknowledged that it may need to raise cash for future development.
Momenta received approval in January for a generic form of the multiple sclerosis drug Copaxone® (glatiramer acetate). The approval of this agent, produced in partnership with Sandoz, had been delayed because of manufacturing issues. The company recognizes that the entry of Mylan (ironically) into this market may hinder its financial outlook.
As a result of these developments, Momenta stated it would entertain a sale of its adalimumab biosimilar “or other assets.”
The Patent Games: Another Sequel Underway
Roche/Genentech has filed suit in Delaware, citing the alleged violation of 37 patents by Amgen in its intent to market its biosimilar version of Herceptin®.
The litigation was filed in response to Amgen’s stated intention of launching their product in October 2018, based on a May approval. Unfortunately, the Food and Drug Administration decided not to approve Amgen and Allergan’s initial 351(k) application in early June.
Roche has been engaged with Pfizer and the team of Celltrion and Teva on their trastuzumab biosimilars as well.
Samsung Bioepis and Biogen has reached a deal with Abbvie that would enable it to market its biosimilar adalimumab (should it be granted approval) in June 2023. This is the second deal Abbvie has made with a potential competitor, confirming the solidity of its patent wall. The European patent expires in October 2018, and competitors will be able to sell biosimilars over the pond unhindered at that time.
However, without competition, most expect unencumbered price increases until a US biosimilar introduction. In other words, biosimilars will not make an appreciable impact on the cost of adalimumab in the US market, unless another biosimilar manufacturer decides to launch at risk in the near future.
A Deal Prior to FDA Approval
The agent, SB5 has not yet been filed for approval in the US. Samsung filed its application for approval in the EU in July 2016 and was authorized by the European Medical Agency in August 2017. Biogen will market the agent for Samsung, whenever it is launched.
Amgen inked a deal with Abbvie in September 2017, effectively ending its patent battle. This deal gives Amgen a jump on other competitors that reach settlements with Abbvie, by allowing a launch in January 2023. In addition, other manufacturers are working on adalimumab biosimilars, including Coherus and Sandoz. The biggest question though is Boehringer Ingelheim’s move, as they have the only other FDA-approved adalimumab biosimilar approved on the marketplace (but also unlaunched). Boehringer responded to our request but declined to comment on its plans moving forward with the product, including a targeted launch date.
Without Competition, Expect 45% Jump in WAC Price
As addressed earlier in this space, the time to effective competition for a US biosimilar adalimumab is crucial. Abbvie’s annual global revenue on the product may reach as much as $21 billion, with the last price increase registered in January, at 9.7%. Assuming Abbvie sticks to its pledge of no more than one
10% price increase per year, that would result in a wholesale acquisition cost (WAC) of more than $52,000 at the close of 2022, or a 45% jump from today’s WAC. This figure does not reflect individual negotiated rates (including rebates) that health plans and insurers actually pay. Yet, it does roughly indicate what type of discount will be necessary when biosimilars reach the market to simply attain the cost paid in 2018—that is, no more savings. Without competition before 2023, this may be the one area where payers pray for a rapid and bracing race to the bottom on price once 2023 rolls around. With Abbvie’s hand continuing on the tiller, don’t plan on it.
In other biosimilar news…Celltrion acknowledged that it is seeking to rectify the manufacturing plant issues that torpedoed its FDA approval of biosimilars for trastuzumab and rituximab. In the statement, it noted, “Celltrion is confident that the issues raised by the FDA will be resolved in a timely manner.
We can confirm that the resubmission will be in-place relatively soon. Then, we are expecting approvals in 6 months after resubmission according to regulatory timeline.”