Savvy Move or Illegal Anticompetitive Action?

Merck, which markets Remicade® in Europe, may have stepped over an anticompetitive line when Pfizer’s Inflectra® biosimilar was first made available, according to the U.K.’s Competition and Markets Authority. In the US, however, this activity would be considered routine. Certainly, nothing prevents this action and it would be fully expected, in terms of net costs.

According the UK’s Competition and Markets Authority, Merck took unfair advantage of “dominant position through a discount scheme for Remicade that was likely to restrict competition” from the biosimilar infliximab when it was launched in 2015. In this scheme, the drugmaker “unfairly” discounted the product to customers who remained loyal to the product.

Is this really different than offering rebates for preferred positioning? Anecdotal reports in the US indicate that Janssen Biotech, which markets the originator agent in North America, has taken similar action with rebates against Inflectra® (infliximab-dyyb). In fact, Amgen did the same to ward off competition from Zarxio® (filgrastim-sndz). In their cases, they did not discount the wholesale acquisition cost (WAC) to meet the biosimilars’ but simply increased the rebate to yield an equivalent net cost.

This action may be more attractive because it may have fewer implications for “best pricing” discounts required by Medicaid and other payers. Certainly, the maker of the originator product can cut their WAC costs if they desired; at the biosimilars’ modest 15% discounts, this would simply roll pricing back to 2015 levels.

In other news…A case report has been published from New York City, in which a patient switching from the reference infliximab agent to the biosimilar version experienced papulosquamous lesions a few days after the change in medication. Skin biopsy revealed the existence of a lichenoid eruption. This adverse event has not been cited previously in the literature with the reference agent Inflectra®. The direct cause of the drug reaction is unknown but further monitoring is warranted, according to the authors.

On June 2, the European Medicines Agency accepted Sandoz’s application for biosimilar infliximab and adalimumab. Sandoz has not filed a 351(k) application with the US Food and Drug Administration for either product.

Pfizer’s Epogen® Biosimilar Gets FDA Advisory Committee Backing

Pfizer purchased Hospira in 2015, and one of its prizes was a biosimilar version of Epogen® and Procrit® that was already being reviewed by the Food and Drug Administration (FDA). The FDA rejected that 351(k) application and issued a complete response letter. Pfizer’s Hospira unit resubmitted its application for its Retacrit™ version of epoetin alpha in 2016. They received good news this week from the agency.

According to the FDA’s staffers’ summary released ahead of the May 25th Oncology Advisory Committee review, Retacrit fulfilled the requirements for biosimilarity. Today, the Advisory Committee added further support to this conclusion by voting 14-1 to recommend approval for all extrapolated indications, despite some safety concerns expressed by committee members.

According to the staff review, “The totality of analytical data support the determination that ‘Epoetin Hospira’ is highly similar to US-licensed Epogen/Procrit notwithstanding minor differences in clinically inactive components.” Nor were any clinically meaningful differences in immunogenicity risk found. The FDA staff review documents also concluded that Retacrit’s biosimilarity evidence supports extrapolation across its intended indications.

Last month, the Food and Drug Administration removed the Risk Evaluation and Mitigation Strategy (REMS) on the originator product, indicating that it is no longer necessary to “ensure that the benefits of Epogen/Procrit and Aranesp® outweigh the risks of shortened overall survival and/or increased risk of tumor progression or recurrence, for the treatment of anemia associated with myelosuppressive chemotherapy.” The originator agent has been linked with cardiovascular safety concerns, which has affected utilization of epoetin alpha over the years.

The first epoetin biosimilars were approved for use in Europe in 2007; a tremendous amount of real-world data have accumulated on their use. However, the FDA Oncology Advisory Committee cannot consider this in their decision.

Members of the FDA Committee expressed “residual concerns with immunogenicity and safety.” For example, patients with chronic kidney disease who require hemodialysis may have a reduced response to Retacrit.

The rather unique “dual” originator products (Epogen/Procrit) resulted from a duel in the 1990s between Amgen and Johnson & Johnson. Amgen originally manufactured the product in the late 1980s and licensed it to J&J’s Ortho Biotech unit. A stormy relationship developed, with lawsuits passed back and forth. The result was a licensing agreement that the drug would be manufactured under license (sounds a bit like a biosimilar, doesn’t it?) by each company for different indications.

The Pitfalls of Pinning Savings on Biosimilars

With the recent capitulation by the Centers for Medicare and Medicaid (CMS) that its part B pilot on value-based purchasing was not going to be implemented, another organization has proposed 2 other avenues to value-based purchasing, which it thinks will encourage biosimilar use and save the part B program billions.

The Pew Charitable Trusts acknowledge the core problem, that payment of average sales price (ASP) plus 4.3% encourages use of the higher priced drug. To address this, Pew offers a consolidated rate plan or a least costly alternative (LCA) plan. They demonstrated the savings that could accrue with either by utilizing an economic model based on the introduction of 5 major biosimilars (1 already approved [infliximab], 3 filed for approval [bevacizumab, pegfilgrastim, and trastuzumab], and 1 not yet under review [rituximab]). Under the model’s assumptions (a few of which are questionable), either approach would cut costs dramatically with just these 5 biosimilars.

Under a consolidated payment rate, CMS reimbursements would be based on a volume-weighted ASP of all reference and biosimilar prescribing, similar to what is used in the conventional brand–generic arena. Pew suggests that “Part B drug spending could be reduced if providers responded by increasing their use of biosimilars over reference biologics (or increasing the use of the reference product if it were available at lower cost… A consolidated payment approach, which would effectively decrease Medicare payment for higher-cost reference biologics and increase payment for lower-cost biosimilars, would create a financial incentive for providers to switch to the latter.”

The second approach is the least-costly alternative, where the payment rate for a higher-cost therapy is set at the payment of a lower-cost, therapeutically comparable alternative—a form of maximum allowable cost (MAC) used in the generic marketplace.

Either approach would depend on the substitutability of a biosimilar for a biologic, as well as an acknowledgement that if the part B payment is lower than the providers’ purchase cost, they will avoid treating part B patients who need these agents and send them to potentially more expensive treatment settings.

Based on these two alternative payment policies, the Pew Charitable Trusts believes that the part B program can save, based on 2014 Medicare expenditures for the 5 reference products, $4.32 billion (or a 21% savings) with the consolidated payment approach and $3.56 billion (or a 35% savings) with the LCA.

These savings figures are unlikely, however, because the devil is in the details, once again. A few key assumptions are important to note:

These 5 biologics are assumed to have lost exclusivity and patent protection, and to have begun facing competition from biosimilars. The time horizon may be problematic here, as clearing the patent litigation is taking far longer than expected, meaning that launches are experiencing unanticipated delays, unless the manufacturer decides to launch “at risk.”

The price of each reference biologic remains constant at the average of its 2014 payment rate. Reference biologic and biosimilar ASPs do not change during the year. Unfortunately, we know this is not the case, as several biologics facing the possibility of biosimilar competition have been subject to alarming price increases, often twice a year, which affect the ASPs.

Biosimilar prices are 35% lower than those of reference biologics. The authors of the analysis based their assumption on pricing differentials found in Europe. So far, the pricing differential of 15% for the 2 launched biosimilars would result in minimal savings, according to the Pew Charitable Trusts’ sensitivity analysis. A 35% decrease may not be evident until competition intensifies, with more than 1 biosimilar available for the reference product.

Under the current payment policy, use of biosimilars is 50% of the total biologic utilization. This assumption is also based on the uptake in Europe, and will not likely be seen in the US without steep price discounts.

Biosimilar prices and uptake are not affected by the number of biosimilars available. The launch of multiple biosimilars for the same reference biologic does not create any additional effect on prices or utilization. This would seem to violate a basic precept of competition in this area, but it could mean that model savings are understated. We’ll have to wait and see how far prices are driven down by additional competition.

The concept of a value-based payment model, which would help encourage use of the lower priced, effective product, is laudable, but savings calculated based on economic modeling (here and for other estimates of biosimilar adoption) have been overly optimistic. Perhaps the numbers pan out over the long term, but today, they may not present a strong enough case to influence CMS or legislative action.

ICER: Current Biologics for Rheumatoid Arthritis Well off the Mark for Cost Effectiveness

The Institute for Clinical Effectiveness and Research (ICER) released its report on biologic treatment of rheumatoid arthritis on April 10th, and it wasn’t pretty. The group, which assesses the value of therapies based on effectiveness and cost, found that none of the available immunomodulators approach the cost-effectiveness threshold of $100,000 to $150,000 per quality-adjusted life-year (QALY).

Of course, the price of this drug class plays a large role in ICER’s calculation, utilizing a discounted wholesale acquisition cost (WAC) that reflected rebates and discounts. The base WAC was the price obtained from the February 2017 Red Book. Although this figure may not be accurate for individual payers, the conclusion of the study was that Humira® would have to be sold at roughly half its quoted $40,415 annual cost to reach an acceptable level of cost effectiveness. At the current net price used and when used as monotherapy, its cost per QALY was $232,644. AbbVie’s Humira adalimumab originator took the brunt of the heat in the study, because it was considered the most costly anti-TNF inhibitor. However, even Janssen’s Remicade® (infliximab), the least expensive anti-TNF inhibitor cited (at $28,906 per year), was not deemed cost effective, at $202,824 per QALY.

Of any biologic used to treat rheumatoid arthritis, Genentech’s interleukin-6 inhibitor Actemra® (tocilizumab, subcutaneous injection) was deemed to have the best monotherapy cost per QALY, at $168,660.

One issue for the immunomodulator class is that a major component of the calculation‑the number of QALYs over the time horizon (the lifetime of the patient‑was closely bunched. They ranged from 12.95 for adalimumab to 13.35 for tocilizumab IV, compared with 10.75 for conventional DMARDs. These figures were slightly lower when the immunomodulators were added onto conventional DMARD therapy (although drug costs were somewhat lower).

Although the calculation did not consider the real issues of dose escalation for certain medications, a sensitivity analysis showed that virtually under all scenarios, the biologic drugs failed to meet the ICER threshold for cost effectiveness. However, it should be pointed out that ICER’s evidence of efficacy was based on patients achieving a fairly low standard: 20% improvement in American College of Rheumatology scores. Therefore, the actual cost to treat patients to a higher standard of improvement should be greater.

The evaluation was done by the New England Comparative Effectiveness Public Advisory Council, an ICER group. According to ICER’s value-based benchmark prices for these targeted immunotherapies, WAC discounts must be slashed from 29% (for tocilizumab subcutaneous) to 55% (for adalimumab) to reach the $150,000 cost per QALY level. In other words, for a biosimilar of Humira to be deemed cost effective by today’s reckoning, it would have to require a WAC discount (or net cost through rebating) of 55% below that of February’s Humira pricing.

This magnitude of reduction in net costs would effectively bend the specialty cost curve in the US. However, without several biosimilar competitors for the same drug, this is unlikely for the monoclonal antibodies. Cost reductions of 50% or more have been seen in certain European countries for first-generation biosimilars, but this would represent an alarming “race to the bottom” for US manufacturers and might dissuade future biosimilar development.

Biosimilar Immunogenicity, Antibodies, and Extrapolation

Based on the clinical studies to date, most clinicians and policy makers would be surprised if a biosimilar did not yield the same patient efficacy outcomes as the originator biologic. We’ve become accustomed to seeing these equivalent results. However, one of the greatest concerns of physicians and patients in biosimilar development has been the potential safety of the biosimilar when it replaces an originator product.

This concern is largely driven by the type of immunogenetic response the biosimilar molecule might elicit. What is the likelihood that it will result in the production of neutralizing antibodies, which would affect the clinical effectiveness of the product? The appearance of antidrug antibodies could theoretically cause serious immunogenic reactions, beyond just injection-site reactions, including anaphylaxis. Years of experience gained in the US and Europe with the first generation of approved biosimilars (filgrastim, epoetin, etc) have demonstrated that these concerns are unfounded. The question is just beginning to be addressed for the first biosimilar monoclonal antibodies approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). Clinical studies of patients who received Inflectra®, Amjevita®, or Erelzi® showed that immunogenicity was not significantly different between these and the originator products. However, their use for other approved autoimmune disorders (i.e., extrapolation) seem to concern those clinicians expressing discomfort with biosimilar prescribing. Usually, studies of the biosimilar do not address ankylosing spondylitis if the principal clinical studies involved rheumatoid arthritis. This is why the FDA weighs so heavily the importance of analyzing the equivalence of a compound’s structure and characterization. Even these characterizations do not necessarily predict the risk of immunogenicity in practice.

According to the FDA, a head-to-head study in treatment-naïve patients is the most sensitive way to detect potential immunogenicity differences. The FDA believes, however, that a single crossover design, in a subgroup of patients, from originator to biosimilar agent, should help quantify the immunogenicity risk. Critical measurements include the formation of antibodies (measurement of their concentrations or titers), how quickly they develop and how long they persist, and their implications for pharmacokinetics and clinical sequelae. Additionally, researchers should monitor for the neutralization by antibodies of the drug’s activity.

An interesting question that could be raised is whether the immunogenicity of the product varies in patients with different autoimmune disorders (e.g., Crohn’s disease vs. rheumatoid arthritis). Although this has not been extensively studied, the use to date of Inflectra®, for instance, in its various indications, has not revealed a significant problem.

The key is that biosimilars in clinical trials and in experience have not elicited immunogenicity responses that are significantly or clinically different than those of the originator. Comprehensive efforts at tracking and surveillance postmarketing will either put these concerns to rest or raise red flags, rather quickly.

Action at the Capitol to Improve Access to Biologic Samples by Biosimilar Developers?

The Trump Administration has indicated a desire to streamline marketplace rules to improve the efficiency of the Food and Drug Administration (FDA) and to enhance manufacturers’ access to the marketplace. “President Trump issued an executive order to this effect,” said Mary Jo Carden, RPh, JD, Vice President of Legislative and Pharmacy Affairs, Academy of Managed Care Pharmacy (AMCP). But “what that means is still a question.”Image result for Mary Jo Carden

Efforts are underway to clear away a roadblock to manufacturers who are trying to bring a competitive biosimilar to the marketplace. Step 1 in the process of building a biosimilar, before a drugmaker can begin to develop and characterize a biosimilar version of an originator, is to obtain samples of the licensed biologic. This is not as simple as it sounds. Those companies producing the originator may be unwilling to provide samples or charge extremely high rates for the use of their product, as a way of stalling competition. Some manufacturers have used REMS and internal distribution restrictions as a reason not to sell to biosimilar drug developers.Image result for US Capitol

Reginia Grayson Benjamin, JD, Director of Legislative Affairs for the Academy, said that two separate initiatives are being developed in Congress to address this problem. First introduced in June 2016 by Senator Patrick Leahy (D-VT) (S. 3056), the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, will need to be reintroduced in 2017. It is an effort to assist competition in the biologics market, by facilitating entry of biosimilars (and small-molecule generics). The CREATES Act,” according to Ms. Grayson Benjamin, “seeks a legal solution to the sample access problem, by creating a right to a civil cause of action for failure to provide sufficient quantities of a covered product.”

Second is the Fair Access to Safe and Timely Generics (FAST) Act, which may be reintroduced into the House of Representatives. It was first brought to Congress in June 2015 by Representative Steve Stivers (R-OH) as H.R. 2841, and did not make it out of the Subcommittee on Health. Ms. Grayson pointed out that it is not a companion to the CREATES Act, but it “would create a regulatory solution,” she said.

However, these proposals, which have not yet been formally debated or sent to committee, and other health care–related bills that have been introduced, have received little consideration because of actions surrounding and the ultimate vote to reject the American Health Care Act.

UPDATE: On April 6, H.R. 2051 was introduced in the House by Representative David B. McKinley (R-WV). This is a reboot of the FAST Act, and has been referred to the Referred to the House Committee on Energy and Commerce.

Cost Savings, a Boon to Biotechs, Both, or Neither?

I was watching a You Tube recording of speakers at a recent meeting sponsored by IBD Horizons. Anita Afzali, MD, Co-director of the IBD program at University of Wisconsin’s Harborview Medical Center, presented her arguments for a cautious approach to extrapolation of autoimmune biosimilar agent use in inflammatory bowel disease. One of her concluding slides caught my eye.

Since the testing and approval of biosimilar agents is specifically geared towards demonstrating similarity in analytical characterization and noninferiority in clinical trials, the obvious singular reason for their existence is lower cost. The cost savings associated with the 2 biosimilars marketed to date have not been impressive, both of which being launched at only a 15% discount in wholesale average cost (WAC). In fact, most payers are treating them as new “me-too” brands, not critical medications that save vital specialty drug dollars. True, the manufacturers of Inflectra®, Zarxio®, and Basaglar® (a follow-on biologic) have gotten some contracting wins, but no one is claiming that these few products will significantly affect the cost curve. In fact, this may not occur until multiple biosimilars of the same originator drug are introduced. Only then, may competition reach a critical mass for significant cost savings.

Dr. Afzali’s point, however, was that without these anticipated cost savings, from the payer’s and—more importantly—from the patient’s perspective, “biosimilars will be a multibillion industry to profit insurances [sic], shareholders, and the biotechnology industries, in an abbreviated pathway generated by the Congress and FDA.”

I’m not sure that payers will really profit from it, because they may hesitate to cover, and certainly not strongly encourage, a biosimilar that does not produce savings. Therefore, it is unlikely that Pfizer’s Inflectra will attain blockbuster status without steep discounts or rebates. With more than $8 billion in annual US revenues for adalimumab, however, who is to say that the result wouldn’t be 4 or 5 biosimilars with drug sales exceeding $1 billion? What manufacturer would pass on that opportunity (especially when the cost of bringing the drug to market will be less than $1 billion)? This rosy future for the biosimilar industry can only happen, though, if the medications are approved, reach the market quickly, and patients can (and wish to) access them.

It is clear from Dr. Afzali’s presentation that physicians like her will not jump at the chance to use biosimilars approved on the basis of rheumatoid arthritis clinical studies to treat Crohn’s disease. That level of comfort will only come with time and experience. The problem is, biosimilars may not have a great deal of time, if the payers and patients are not convinced of the cost savings.

Real-World Evidence Shows Biosimilar Epoetin Outcomes as Good as the Originator

The erythropoiesis-stimulating agents (ESAs) are among the first biosimilars approved for use in Europe, a decade ago. As more real-world evidence accumulates on the comparable outcomes of several classes of biosimilars, support increases for their utilization abroad. This past week, researchers from Rome, using a real-time patient registry, have confirmed the safety and efficacy of biosimilar versions of erythropoiesis-stimulating agents (ESAs) compared with the originator product (epoetin-alpha).

Dr. Francesco Trotta, Department of Epidemiology, Lazio Regional Health Service, Rome, led a team of investigators who evaluated the use of ESAs in nearly 13,500 patients with chronic kidney disease or undergoing treatment for cancer in a region of Italy (total population, 6 million) over a 3-year period, assuming a 6-month course of the agents. They assessed all-cause mortality and need for blood transfusion and the incidence of major cardiovascular events and blood dyscrasia, which comprised a composite endpoint of effectiveness and safety.

The results of this study were published in BMJ Open. In comparing 3 ESA biosimilars (Abseamed®, Binocrit®, and Retacrit®) to the epoetin alpha originator drug (Eprex®), the researchers found that in patients with chronic kidney disease, the risk estimates for the effectiveness and safety measures were not significantly different. Using a composite outcome, the biosimilars demonstrated an adjusted hazard ratio of 1.02 compared with Eprex. The biosimilars were also compared with other ESAs, including darbapoetin alpha, epoetin beta, epoetin theta, and methoxypolyethyleneglycol-epoetin beta. Though not considered biosimilars to these agents, the epoetin alpha biosimilars recorded an adjusted hazard ratio of 1.09 compared with these other ESAs. For patients receiving oncology treatment, the biosimilars demonstrated a better hazard ratio for the all-cause mortality outcome (adjusted HR, 0.82), which was on the “margin of statistical significance.” In terms of the composite outcome, the biosimilars exhibited a slightly improved adjusted hazard ratio (0.91). Subgroup analysis revealed some minor differences in outcomes, but none that would alter a patient’s clinical approach.

The authors concluded, “In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes measured during the follow-up period.”

These results should not be surprising based on the success (and proliferation) of the ESA class since 2007. The fact that a US version of epoetin alpha has not yet been approved is surprising: Pfizer’s Retacrit was submitted in 2014, with hopes of being the first biosimilar on the market, but a complete response letter from the FDA the following year short circuited this plan. No other epoetin biosimilar is on record as being filed for approval with the FDA at this time.

Mylan Clears the Way to Potential Trastuzumab Biosimilar Launch

A settlement reached with Genentech and F. Hoffmann-La Roche Ltd. should allow Mylan to launch its biosimilar version of Herceptin® soon after the completion of its Food and Drug Administration (FDA) review in September. Mylan, which holds a partnership agreement with Biocon, will market the new trastuzumab biosimilar once approved.

Under the agreement, Mylan will have a global license to commercialize the agent (except in Brazil, Japan, and Mexico). The agreement cancels all remaining patent litigation, including Mylan’s Inter Partes Review, which sought to invalidate 2 key patents on trastuzumab. It is assumed that Genentech and Hoffman-LaRoche will obtain royalty payments as part of the settlement, but terms of the deal were not released.

Filed in November, the current deadline for FDA action on Mylan’s 351(k) application is September 3, 2017. Theirs is the first (and only) trastuzumab biosimilar application filed in the US. In a press release, Mylan CEO Heather Bresch stated, “There is an unmet need for access to more affordable versions of biologic products such as trastuzumab. We look forward to enhancing access to this important treatment option, which complements our comprehensive cancer care offerings, in the US and around the world.”

Mylan and Biocon’s partnership breaks out commercial control as follows: Mylan will sell the product in North America, Australia and New Zealand, and in Europe; Biocon will hold rights to sell the product elsewhere.

Assuming the FDA approves the agent according to schedule, this would represent the first biosimilar agent to be marketed in the US for the direct treatment of cancer. However, Europe may see their first oncological biosimilar earlier: Mylan submitted its application for licensing with the European Medicines Agency (EMA) in November 2016, Celltrion’s CT-P6 was also submitted that month in Europe, but Samsung Bioepis applied for approval in August 2016 and may be the first reviewed by EMA.


Predicting Coverage Changes in the Psoriasis Field: Will Biosimilars Play a Significant Role?

If you haven’t noticed, there is a good bit of action occurring on the plaque psoriasis treatment front. One long-used anti-TNF drug (Cimzia®) may be nearing approval of its  psoriasis indication, one new interleukin drug was recently approved (brodalumab), and another interleukin inhibitor is being considered by the U.S. Food and Drug Administration for approval later this year (guselkumab).

The general idea that the interleukin inhibitors have superior efficacy to the anti-TNF agents is becoming more accepted, but this is rarely reflected in the formulary preferences of health plans and insurers. Typically, these plans prefer both adalimumab (Humira®) and etanercept (Enbrel®). As with most therapeutic classes, this is the result of marketshare and net cost. AbbVie maintains the number 1 position, meaning that forcing a change or encouraging the use of an alternative preferred product is more difficult—moving significant marketshare to another agent will take considerable resources, and competitors’ pricing may not justify this battle.

Image result for Psoriasis Activity Severity Index

There is evidence that etanercept is not the most efficacious of the anti-TNF inhibitors for the treatment of moderate-to-severe psoriasis, but few health plans manage the autoimmune category by specific indication (other than arming themselves with the usual prior authorization criteria). For instance, it may be a stretch to assume that FDA approval of a new psoriasis indication for a covered biologic will suddenly force plans to change its formulary positioning of the product.

Assuming that the interleukins do represent a better chance for complete resolution of plaque psoriasis symptoms (i.e., PASI 100 vs. PASI 75), albeit at a higher net cost, it means that biosimilars for etanercept or adalimumab won’t change the clinical outlook for patients. For example, a new study announced at this week’s American Association of Dermatology meetings found that Lilly’s interleukin-17A inhibitor ixekizumab (Talz®) beat Janssen’s interleukin-12/23 inhibitor ustekinumab (Stelara®) in a head-to-head trial. The point is that anti-TNFs cannot match this level of efficacy (based on PASI scores): 83% of those treated with the interleukin-17A product achieved PASI 90 scores compared with 59% of those treated with the comparator; 49% of those treated with interleukin-17A achieved PASI 100 scores compared with 23% of those treated with the interleukin-12/23 inhibitor.

Yet health plans have not decided that the clinical benefits of the interleukins outweigh their higher costs, making them preferred products or available as first-line biologic agents. Marketshare and price are the usual sticking points.

Furthermore, the basic problem of biosimilar pricing still remains. In personal correspondence with several health plan pharmacy directors, the 15% discount offered for Pfizer’s Inflectra®, the only biosimilar anti-TNF available, is easily matched by Janssen for its Remicade® originator. Health plans could actually wind up paying more for an aggressive campaign to replace the originator brand with the biosimilar at current pricing.

This will certainly play a role in deciding whether Enbrel® can be knocked off its preferred positioning perch. With billions of dollars in annual revenue at stake, Amgen will surely take measures to match any modest discount from Sandoz on biosimilar etanercept (or at least get closer to that net-cost neighborhood with increased rebates). This may well be all that is needed to discourage biosimilar uptake on drug formularies.