Jackie Syrop

A study of a managed switching program among patients with inflammatory bowel disease (IBD), who were treated with infliximab (Remicade) and then switched to its biosimilar CT-P13 infliximab (Inflectra/Remsima), found that switching delivered significant cost savings and resulted in no significant differences between the 2 medications in terms of drug persistence, side effects, adverse reactions, disease activity, or biochemical response. The study has been published in the 

The study followed 143 patients with IBD (118, Crohn’s disease; 23, ulcerative colitis; and 2, unclassified IBD), all of whom had been on reference infliximab and agreed to participate in the switching program. Evaluation outcomes included drug persistence, changes in drug acquisition costs, patient-reported side effects, adverse events, patient outcomes assessed using the IBD-control Patient-Reported Outcome Measures questionnaire (IBD-Control-8), serum drug and antibody levels, and routinely collected biochemical markers. Patients reported a similar incidence of side effects before and after the switch. No clinically significant differences were observed in mean C-reaction protein, albumin, hemoglobin levels, or platelet and white cell counts after the switch to CT-P13. The mean IBD-control-8 score improved from 10.4 to 11.2 (

 = .041). There was no significant difference in drug persistence between biosimilar and reference infliximab (

 = .94) and no increase in immunogenic response to the biosimilar.

Investment in the new program, including salary for an IBD specialist nurse and other support staff, was about 12% of expected cost savings. The analysis showed substantial cost savings to the health economy, part of which has been reinvested in not only delivering the program but also improving the service and quality of care for the whole IBD patient population in Southampton—not just for biologics-treated patients. The authors write that drug acquisition costs fell by £40,000 to £60,000 pounds (approximately $50,000 to $75,000) after the managed switching program began.

In the European Union (EU), interchangeability of approved biosimilars with reference biologics does not require prescriber approval. However, in the United States, pharmacy-level switching is not allowed unless a biosimilar has the FDA’s interchangeable designation; none of the US-approved biosimilars are yet deemed interchangeable. Switching studies such as this are likely to play an important role in demonstrating the interchangeability of US biosimilars and reference drugs, according to the recently issued FDA draft guidance for pharma.

 Some US experts consider biosimilar interchangeability critical to the successful market uptake of biosimilars and key to bringing down prices of biosimilars to significantly lower levels than reference drugs. However, other analysts suggest that interchangeability may become less important for commercial competitiveness because some 2017 formularies are already choosing biosimilars instead of reference brands.

Surveys of US pharmacists found that nearly three-quarters said they would feel comfortable or very confident substituting an interchangeable biosimilar for its branded biologic counterpart if the 2 products share the same nonproprietary name, had precise product identification, and complete and transparent labeling to ease follow-up on patient outcomes and safety.

Physicians, however, have expressed concerns about switching patients from reference biologics to biosimilars because biosimilars, unlike generics of non-biologic drugs, cannot be exact copies of biologics because of the complex nature of biological drug proteins.

 Surveys suggest the majority of physicians in the EU (63%) are open to the idea of biosimilar substitution.

US physicians and patients appear to have a little farther to go in acceptance of biosimilars in place of reference medications.

A 2015 survey of US physicians showed less (48%) support for biosimilar substitution; physicians say they are concerned patients could develop immunogenic reactions to biosimilars, forever threatening treatment response to the drug.

 Patients who are satisfied with their therapeutic response to the reference biologic may resist switching to biosimilars because of the unknown experience with a biosimilar.

Education is key to building up acceptance of biosimilars among patients and physicians because patients are open to shared decision-making with physicians—if physicians are open to using biosimilars, patients tend to trust their judgment.

Razanskaite V, Bettey M, Downey L, et al. Biosimilar infliximab in inflammatory bowel disease: outcomes of a managed switching programme [published online January 27, 2017]. 

Felix AE, Gupta A, Cohen J, Riggs K. Barriers to market uptake of biosimilars in the US. 

Slone WL, Murphy MF. “Stop the presses”: biosimilar development & interchangeability. Worldwide Clinical Trials website. Worldwide Clinical Trials website. 

www.worldwide.com/blog/2017/02/stop-presses-biosimilar-development-interchangeability/?utm_source=6326&utm_medium=Twitter&utm_campaign=voicestorm

Survey: Pharmacists are most confident substituting interchangeable biosimilars for brand biologics when products share nonproprietary name. 

http://www.pharmacytimes.com/association-news/survey-pharmacists-are-most-confident-substituting-interchangeable-biosimilars-for-brand-biologics-when-products-share-nonproprietary-name

. Published February 27, 2015. Accessed February 21, 2017.

ASBM releases pharmacist survey: findings show strong support for distinguishable names for biologics and need for transparency in labeling. Biosimilar Development website. 

www.biosimilardevelopment.com/doc/asbm-pharmacist-distinguishable-biologics-transparency-in-labeling-0001

. Published October 13, 2015. Accessed February 21, 2017.

McDonald C. Biosimilars in the US: five potential sticking points. 

 www.pharmexec.com/biosimilars-us-five-potential-sticking-points

. Published April 21, 2015Accessed February 21, 2017.

Metcalf M. Biosimilars: bringing patients into the conversation. eyeforpharma website. 

http://social.eyeforpharma.com/column/biosimilars-bringing-patients-conversation

. Published January 20, 2017. Accessed February 17, 2017.

Articles

Will US Follow UK on Managed Biosimilar Switching of IBD Patients on Infliximab?

The Biosimilars Council, a division of the Association for Accessible Medicines (previously the Generic Pharmaceutical Association), 

an amicus brief with the Supreme Court arguing that the biologic manufacturers should not get an additional 6 months of market exclusivity beyond the current 12 years. Sandoz received 

of filgrastim-sndz (Zarxio), a biosimilar of Amgen’s reference filgrastim Neupogen, in March 2015.

is in advance of the Court’s April 26th hearing of oral arguments for the dispute between Sandoz and Amgen over whether a Federal Circuit Court ruled properly in granting an additional 6 months of exclusivity to biologic sponsors based on a provision of the Biologics Price Competition and Innovation Act of 2009 (BPCIA). The Biosimilars Council noted that Congress gave sponsors a period of exclusivity that is 12 years and 12 years only, extendable only based on pediatric research: “No one referred to the period as 12 1/2 years, as respondents would have it.”

Under the BPCIA, biosimilar applicants must provide notice to the reference product sponsor no later than 180 days before the date of the first commercial marketing of the biological product. Sandoz argues that the Federal Circuit “turned this mere notice provision into a grant of 180 days of additional exclusivity for all biological products beyond the exclusivity period Congress expressly provided—delaying the launch of all future biosimilars by six months.”

The Biosimilars Council argues that the notice allows patent litigation to precede a biosimilar’s launch, not to “make the parties wait for a ‘fully-crystallized controversy’ before litigation begins.”

The additional 6 months of exclusivity would translate into a huge loss of potential cost savings for patients and payers. The brief states, “For an individual Medicare Part B beneficiary responsible for thousands of dollars per year in cost-sharing payments for a biologic drug that costs $50,000 or even $200,000 per year, or for a patient with private insurance and similar cost-sharing obligations, the six-month savings could mean the difference between selecting and forgoing much-needed therapies for serious illnesses.” Sandoz believes that the additional exclusivity period will shift billions of dollars from patients, federal programs, and insurance premiums over to biologic sponsors.

For manufacturers of these biosimilars, too, the extra 6 months of market exclusivity is a very significant issue, because developing and manufacturing biosimilars is particularly costly and time consuming (an average cost of $100 million and $200 million, over a period of 8 to 10 years), on top of the $250 million to $1 billion investment required for companies to build, equip, and qualify manufacturing facilities. “A further delay before companies can begin to recover their substantial investment is likely to shrink the universe of potential candidates still further,” the brief adds.

However, the Biosimilars Council said the Federal Circuit Court was correct to hold that when a biosimilar applicant decides not to provide its confidential information to a biologic sponsor, the sponsor’s sole remedy is the one set out in the statute, which is a patent infringement action. Just last week, Genentech 

 against Amgen for withholding this information. The United States has the world’s longest period of exclusivity for biologics. Europe has 10 years; Canada, 8; and other countries (Australia, New Zealand, Japan, and South Korea) have 5 or 6 years of market exclusivity. 

Biosimilars Council Wants Elimination of 6-Month Exclusivity for Biologics 

 for review Mylan’s (and Mylan’s biosimilars partner Biocon’s) Biologics License Application (BLA) for the proposed biosimilar to Amgen’s Neulasta (pegfilgrastim), currently called  MYL-1401H. The proposed biosimilar to Neulasta is used to reduce the duration of neutropenia and the incidence of fever associated with neutropenia, in adults treated with chemotherapy for certain cancers. The FDA’s goal for a decision on the application, based on the User Fee Act, is October 9, 2017.

Pegfilgrastim is a long-acting version of Amgen’s Neupogen (filgrastim). Biosimilars of Amgen’s filgrastim have been on the European market for years, and Sandoz’s biosimilar of Neupogen (Zarxio) is the first US biosimilar to have been approved and marketed. However, Neulasta is a bigger and more complex biologic than Neupogen, and biosimilar makers have not yet been successful in gaining FDA or European Medicines Agency (EMA) approval for proposed biosimilars to Neulasta.

The complexity of Neulasta is largely due to the presence of the polyethylene glycol (PEG) molecule, which is bonded to filgrastim. The presence of PEG on filgrastim slows the rate at which the molecule is metabolized and eliminated from the body, which reduces the frequency of dosing. PEG is what makes Neulasta long acting. However, the presence of PEG also makes it more difficult to develop a biosimilar to Neulasta. Other companies have experienced rejections of their applications for Neulasta biosimilars in the United States and in Europe. The FDA 

 Sandoz’s application for its Neulasta biosimilar in July 2016; Sandoz may be submitting additional data to the FDA in support of the application in 2018. The company has also had difficulties in its European submission for a Neulasta biosimilar, and withdrew its application to the EMA for a Neulasta biosimilar. Sandoz will not be able to provide additional data to the EMA within that agency’s permitted time frame.

Other drug makers have faced similar problems gaining approvals of their Neulasta biosimilars, including Gedeon Richter, which withdrew its application to the EMA in 2016, and Apotex, which is still waiting for an FDA advisory committee meeting on its Neulasta biosimilar, although its application was accepted for review in December 2014. Several other Neulasta biosimilars are also being reviewed by the EMA and FDA, and it remains to be seen how the products will fare.

FDA Accepts Mylan-Biocon Pegfilgrastim Biosimilar Application

 with the recent FDA final guidance on how biosimilars and their reference biologics are to be named. In comments about the posted guidance, the companies criticized the 

, which requires retroactive changes to the nonproprietary names of existing biologics and biosimilars.

The FDA’s guidance specifies that product names are to include a four-letter meaningless suffix after a hyphen that follows the nonproprietary name. The suffix will be a requirement for all previously licensed originator biologics, related biological products, and biosimilars. The addition of the suffixes is part of the FDA’s plan to improve pharmacovigilance for reference biologics and their biosimilars.

“Retroactive application of the naming policy is not only unnecessary ‘for the proper performance of the functions of the agency,’ but it also is likely to undermine FDA’s objectives in adopting distinguishable nonproprietary names, ie, to ensure safe prescribing and robust pharmacovigilance,” AbbVie commented.

Both Novartis and AbbVie said that changing the nonproprietary names of existing products does nothing to support safe prescribing or pharmacovigilance. Novartis disagrees that the revised naming system will improve patient safety. “We believe such suffixes will not provide additional value beyond that of the current naming system, which has been used successfully for over 6 decades,” Novartis added.

AbbVie believes that changing the nonproprietary names of currently marketed products would impose significant burdens on industry, FDA, and the healthcare system that do not arise when manufacturers of both originator and biosimilar products are asked to adopt unique nonproprietary names before product approval.

Other stakeholders also weighed in. CVS Health’s Vice President of Policy and Regulatory Affairs, Donald Dempsey, 

 the FDA’s guidance could have negative effects on the marketplace and slow the development of affordable and accessible biosimilars. The FDA’s rule to create unique names could cause a situation where biosimilars with the same active ingredient but not an identical international nonproprietary name would be in different categories than originator products in provider databases, “creating a situation where each database warehouse would make these decisions independently of other warehouses, resulting in confusion and unnecessary complexity.” The company also expects there to be an impact on member and client website and mobile applications, along with client reporting. “Our mail and specialty pharmacies systems will also be impacted by this guidance,” Dempsey said, and each will have to be carefully assessed and enhanced to avoid negative client and provider impacts or member disruption. CVS Health estimates this effort would cost in excess of $1 million.

The Biologics Prescribers Collaborative, which includes several patient and physician organizations, including the American Gastroenterological Association, Endocrine Society, and the Alliance for Patient Access, commented that 80% of physicians in their groups 

 a meaningful, not random, suffix to be used for the biosimilar name.

Jillanne M. Schulte, JD, director of Federal Regulatory Affairs for the Association of Health-System Pharmacists also 

 on the burden of the FDA naming convention, not simply for drug makers but for others who would have to change current systems to work with the new policy. This would mean hospitals, payers, and providers would need to spend thousands of hours on IT redesign and reprogramming.

AbbVie, Novartis Unhappy With FDA Guidance on Naming Biologics and Biosimilars

 to biosimilars of 2 important anticancer antibodies—the blood cancer treatment rituximab (Rituxan) and breast cancer drug trastuzumab (Herceptin)&mdash;and the arrival of these biosimilars are expected to slash costs and expand patient access to these expensive oncology treatments. Biosimilars of these 2 drugs have previously seen a lot of delays.

While approval of biosimilar rituximab from the European Medicines Agency (EMA) is pending, preparations are being made for the launch of Celltrion’s rituximab biosimilar. The EMA’s 

 shows the agency is assessing 2 rituximab biosimilars and 3 trastuzumab biosimilars. The Mylan/Biocon trastuzumab biosimilar may be first of the 3 to be approved later this year in Europe. (There are biosimilars of both trastuzumab and rituximab in Asia, but Europe would be the first large market for these biosimilars; any launches in the United States are farther in the future.)

Although there are concerns about how quickly physicians and patients will adopt the new trastuzumab and rituximab biosimilars, worries about the ability of European healthcare systems to pay for current and future biologic reference drugs are leading cancer experts and healthcare providers to say they plan to support and use the biosimilars because they will save money and increase patient access. In Britain, the National Health Service (NHS) spends more than £300 million ($375 million) on rituximab and trastuzumab, and recently 

 patients treated in NHS hospitals to get biosimilars in the future. Pharmacists in the country are on board, too. The British Oncology Pharmacy Association recently 

 it was committed to optimizing the use of biosimilars in cancer treatment.

Some experts believe the adoption of trastuzumab and rituximab biosimilars in Europe will follow the model of how doctors there adopted biosimilar anti-tumor necrosis factor (TNF)-alpha drugs, used for rheumatoid arthritis (RA) and other immune disorders. It took a few months for physicians to become comfortable with the first biosimilars, but then demand for them took off. More importantly, competition has substantially driven down prices. Biosimilar anti-TNF-alpha agents now sell at approximately a 50% discount in Europe, and Novartis (it’s Sandoz division develops biosimilars) believes discounts could increase to as much as 75% in some cases. If the pattern for biosimilar RA drugs in Europe holds true, biosimilars for trastuzumab and rituximab are likely to start out at about 30% of the reference product price.

Newly diagnosed cancer patients are expected to be the first to receive the biosimilar anticancer agents. According to biosimilar drug maker Napp Pharmaceuticals, which will sell the Celltrion rituximab biosimilar in Britain, uptake of the drug will not be instant in every area but is expected to be much faster than has been seen in the past with biosimilars.

Herceptin, Rituxan Biosimilars Might Soon Reach Oncologists in Europe

A recently published meta-analysis of the clinical efficacy, safety, and pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha biosimilar agents concludes that the biosimilars had an overall comparable efficacy and safety profile compared with their reference agents in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), supporting their use to treat these conditions.

The investigators searched electronic databases (PubMed/MEDLINE, Google Scholar, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials) and abstracts from medical conferences for randomized controlled trials assessing the efficacy and safety of biosimilars of anti-TNF-alpha agents, compared with their reference agents, in patients with a variety of immune-mediated diseases. The analysis used 9 studies encompassing treatment outcomes in 3291 patients with RA and AS who used infliximab (5 studies), adalimumab (2 studies), and etanercept (2 studies).

One primary outcomes of the study was the rate of clinical response and adverse events among patients treated with biosimilars compared with their reference drugs. Risk ratios of American College of Rheumatology 20% (ACR20) and 70% (ACR70) response were calculated for RA patients, and Assessment of SpondyloArthritis International Society 20% (ASAS20) response rates were calculated for AS patients, respectively. Response rates were analyzed at short (12 to 16 weeks), medium (24 to 30 weeks), and long-term (48 to 54 weeks) intervals. The second outcome studied was the occurrence of anti-drug antibodies (immunogenicity) with the use of biosimilars compared with immunogenicity rates to reference agents at short (14 weeks), medium (up to 24 to 30-weeks or at 30 weeks), and long (48 to 54 weeks)-term periods. Immunogenicity is a concern because it can potentially limit clinical efficacy and safety.

The researchers write that their study is the first to comprehensively analyze and combine the available data by meta-analysis. They conclude that their study showed biosimilars of anti-TNF-alpha agents had overall similar clinical efficacy, safety, and immunogenicity compared with their reference agents in RA and AS up to 54 weeks of follow-up. The only exceptions were that biosimilars of infliximab were associated with an increased risk of upper respiratory tract infection and biosimilars of etanercept showed a significantly lower occurrence of anti-drug antibodies.

The authors believe that their study demonstrated that patients with RA and AS treated with biosimilars had no significant differences in the frequency of overall treatment-emergent adverse events, severe treatment-emergent adverse events, infusion reactions, malignancies, and infections compared with their respective reference biologics. “The results of our study support the use of biosimilars in the treatment of RA and AS,” they conclude.

Komaki Y, Yamada A, Komaki F, et al. Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-α agents in rheumatic diseases; A systematic review and meta-analysis [published online February 14, 2017]. 

 http://dx.doi.org/10.1016/j.jaut.2017.02.003.

Efficacy and Safety of Anti-TNF-alpha Biosimilars Comparable to Reference Drugs in RA and AS

Despite the fact that there are at least 5 biosimilar products with review timelines scheduled to come up for FDA review this year, and several previously rejected applications that could also be in line for review, 2017 may turn out to be a year that will be regarded as “a lull” in biosimilar approvals and marketing in the United States.

 This will further delay the  development of a robust competitive environment with multiple biosimilars of the same reference product, which could potentially result in meaningful price reductions and improved access to important, expensive medications.

The FDA faces a year of changes and unknowns in 2017. There is a March 20 deadline for public comments on the agency’s recently released draft guidance on biosimilar interchangeability—a designation considered key to the long-term success of biosimilars&mdash;but it is not known when (or if) the FDA will make any such interchangeable designations. Another regulatory issue facing the FDA is the need to renew the Biosimilar User Fee Act (BsUFA) program, which expires September 30, 2017. The BsUFA must first be approved by Congress and the Trump Administration before it takes effect. A renewed BsUFA agreement would provide a huge funding boost for biosimilar regulation and review activities, potentially improving FDA’s capacity for much-needed guidance development and educational initiatives for biosimilars.

In addition, several federal court decisions that will be made in 2017 are expected to have a great impact on US biosimilar approvals. The Supreme Court will rule on the Amgen-Sandoz Zarxio dispute over patent information exchange and biosimilar launch provisions in the Biologics Price Competition and Innovation Act (BCPIA). Additional hearings and trials for several other patent cases involving reference pharmaceuticals and biosimilars will affect whether new biosimilars will reach the US market this year. There are also reported to be a large number of BPCIA litigations that promise to be complex and continuing: one is AbbVie’s suit against Amgen over alleged infringement of Humira (adalimumab) patents that will potentially slow any launch of Amgen’s adalimumab biosimilar Amjevita, and the other is Amgen’s patent litigation against Novartis/Sandoz’s Erelzi (etanercept), an Enbrel biosimilar.

Finally, hanging over all of these issues is the possibility that the changes promised by the Trump administration with respect to repealing and replacing the Affordable Care Act (ACA) will affect the BCPIA, which was enacted in 2010 as part of the ACA. There are also questions about the administration’s 

 and whether it will affect the FDA’s user fee-funded positions that affect drug approvals and review.

Sutter S. Biosimilars in 2017: Crowded US FDA review queue, key legal decisions. 

 Legal and Regulatory Decisions Likely to Drive Biosimilar Approvals in 2017

, describes a question raised at the 2017 CBI Biosimilars Summit in Alexandria, Virginia: Is 2017 going to be a “standstill” year for biosimilars? She reports that despite the many positive steps that have been taken to establish the biosimilar industry to date—including recent FDA guidance and several approvals&mdash;its success is still “looking hazy.”

Although small, the conference boasted an impressive array of speakers from a variety of stakeholders including physician and patient groups, payers, small biosimilar companies, and big Pharma, Welch said, and at every event she attended the focus was on the challenges facing the industry and concerns over regulations being established. The theme of the conference was strategic and tactical decisions for long-term success in the biosimilar market. Each presentation was structured as a discussion that aimed to get all attendees interacting with each other and the speaker.

Three themes ran through every session, Welch noted: risk, uncertainty, and frustration. In the biosimilar industry a number of external risks and uncertainty surround patient, physician, and payer response and adoption of biosimilars. Biosimilars are facing litigation and other defensive strategies mounted by originators, as well as market evolution. The United States, often a market leader, is following the rest of the world when it comes to biosimilars, Welch points out. Many unknowns remain with respect to future FDA regulations and the repeal of the Affordable Care Act (ACA). And there is frustration from biosimilar companies and payers that biosimilar uptake is going to be pushed by the payers. Formulary decisions made by CVS and UnitedHealth helped integrate biosimilars into treatments for new patients, but the actions of 2 payers is not necessarily going to be a rule for other payers who wish to wait and watch.

Some health insurers at the conference expressed disappointment in the small discounts offered by biosimilar makers, Welch reported. Small discounts mean that patients are unlikely to realize savings, giving smaller payers more reason to hesitate. Although the insurers understand that it will take time and more competition to drive sharper discounts, Welch explains that their experience with biosimilar pricing is colored by their experience with generic drugs, which offer much steeper discounts. There was too much optimism at the start that biosimilar prices would be lower right off the bat, which reflected a lack of knowledge of the complexity of biosimilars. Concerns over low biosimilar discounts can possibly be mitigated, but it will mean tremendous efforts must be made to communicate with and educate physicians and patients to “sell the biosimilar story,” perhaps dispelling patient concerns about biosimilar efficacy. Another issue to consider is that as reference drug makers negotiate with health insurers to renew contracts for the next year, payers may need to weigh whether savings for the patient can overcome the potential inconvenience of switching therapies.

Developments that are likely to affect the future of the biosimilar market in 2017 include the opportunity to pursue interchangeability. Welch notes that it isn’t likely that there will be an approval and marketing of an interchangeable biosimilar in 2017. There will be a Supreme Court ruling on the “patent dance” and timing of the 180-day notice of biosimilar marketing, however, and there will be a determination of what will happen to the ACA.

“The overarching message I took away from this conference was that it will be key in 2017 for companies to temper expectations and become familiar with uncertainty,” Welch concluded. The biosimilar industry will never have certainty, said summit chairman Edric Engert, senior vice president of biosimilars at Teva. Will 2017 turn out to be a “standstill year?” That depends on how the legal, development, and healthcare challenges play out. As Engert told conference attendees, 2017 may be an inflection point for companies. “We won’t so much be hitting a ‘pause’ button, but 2017 will be a time for many companies to slow down and consider just how involved they wish to be in the biosimilar market.”

Will 2017 Change the Fate of Biosimilars? An Update From the CBI Summit

Inflectra, Pfizer’s infliximab biosimilar to Johnson & Johnson  (J&J)’s Remicade, and the first FDA-approved infliximab biosimilar, became available in the United States in November 2016.

 There is still only a short history of how the first infliximab biosimilar is competing with its reference product, Remicade in the United States, and there is much interest in whether Inflectra has the potential to become a top seller for Pfizer, cut into the blockbuster Remicade’s sales, and potentially offer a cost savings.

Some clues about how Inflectra might compete with Remicade may be seen by looking at fourth-quarter 2016 sales figures. Analysts also look at how the 2 drugs are competing in Europe, where Inflectra, which is also marketed as Remsima, has been available since 2015. Merck markets Remicade in Europe.

In 2015 J&J and Merck reported Remicade sales of $6.56 billion and $1.8 billion, respectively. But in 2016, after infliximab biosimilars launched in both Europe and the United States, sales of the drug fell, first in Europe, and then, in November, in the United States.

Merck reported a year-over-year drop in sales of 29% in 2016, and J&J reported a 1.7% year-over-year drop in US sales of Remicade in the fourth quarter, following a 9.4% year-over-year growth in the third quarter. According to J&J statements, Inflectra is not yet affecting Remicade’s market share, suggesting that J&J may be discounting Remicade’s price in order to maintain market share.

Pfizer’s fourth-quarter earnings showed that its biosimilars’ revenue rose 48% from 1 year ago, largely because of Inflectra’s US market launch in November 2016. In the fourth quarter, Inflectra had $61 million in sales (up from $30 million a year ago) despite the fact that Inflectra is selling in the US at only a 15% discount to Remicade—a reduction that is far lower than the savings Remicade biosimilars offer in Europe, where they have been sold at discounts of 45% and higher.

 The US sales of Inflectra may be relatively lower because, unlike in Europe, it cannot be automatically substituted for Remicade—the FDA has not designated Inflectra as interchangeable with Remicade. In a 2015 interview, Adam Schechter, Merck’s president of Global Human Health and executive vice president, noted that the company was not seeing a major impact from substitution of a biosimilar for Remicade.

Thus, the 15% discount on Inflectra, viewed as an incentive to attract new patients to start on the biosimilar, may not be enough to influence stable patients to switch from Remicade. If health insurance companies embrace Inflectra because it is a lower-priced option for Remicade, Inflectra could eventually take more than the 10% to 15% of a US market share, which J&J estimates to be $4.4 billion.

Dangi-Garimella S. Biosimilar price wars: Pfizer's biosimilar to Remicade will be cheaper. 

http://www.ajmc.com/newsroom/biosimilar-price-wars-pfizers-biosimilar-to-remicade-will-be-cheaper

. Published October 18, 2016. Accessed February 8, 2017.

Campbell T. Pfizer’s new biosimilar is off and running. 

https://www.fool.com/investing/2017/02/04/pfizers-new-biosimilar-is-off-and-running.aspx

. Published February 4, 2017. Accessed February 7, 2017.

Mukherjee S. Why these copycat drugs aren’t slashing best-sellers’ prices. 

http://fortune.com/2016/10/18/pfizer-johnson-johnson-remicade-biosimilar

. Published October 18, 2016. Accessed February 7, 2017.

Serebrov M. Market impact of first biosimilar Mab contained—so far. 

http://www.bioworld.com/content/market-impact-first-biosimilar-mab-contained-—-so-far-2

. Published August 17, 2015. Accessed February 7, 2017.

How Will Pfizer's Infliximab Biosimilar Compete With Remicade?

Inflammatory bowel disease (IBD) specialists from the European Crohn’s and Colitis Organization (ECCO) issued a new consensus statement that supports switching patients from Remicade, the reference infliximab medication, to a biosimilar infliximab (in Europe, Inflectra/Remsima, Flixabi).

The new position statement, issued at the ECCO meeting in Vienna, Austria, in October 2016, represents a significant shift from the group’s 2014 position statement, which acknowledged the potential cost-savings from using biosimilars and the increased access to potentially life-changing medicines, but did not advocate switching. Rather, the 

 said there was a need for caution concerning the use of biosimilars and that switching from the originator infliximab biologic to biosimilars was inappropriate.

The new ECCO consensus statement on biosimilars states that based on the regulatory guidance from the European Medicines Agency (EMA) and evidence about the efficacy and safety of biosimilars in IBD patients, ECCO supports switching from the originator biological infliximab to the biosimilar. “When a biosimilar product is registered in the European Union, it is considered to be as efficacious as the reference product when used in accordance with the information provided in the Summary of Product Characteristics,” the statement declares.

According to the updated consensus statement, biosimilarity is more sensitively characterized by suitable 

 assays than through performing clinical studies. ECCO supports using clinical studies of equivalence in the medication’s “most sensitive” indication to provide a basis for extrapolating its use for other indications, and states that data for the usage of biosimilars in IBD can be extrapolated from another sensitive indication. However, other professional groups of European gastroenterologist—including 

 in gastroenterology, hepatology, and nutrition and 2 Spanish medical societies—have issued 

 expressing concern about extrapolating indications using clinical data from patients with rheumatoid arthritis to patients with IBD.

The consensus statement also points out that adverse events and loss of response due to immunogenicity to a biologic cannot be expected to be overcome with a biosimilar of the same molecule.

The ECCO statement explains that demonstrating the safety of biosimilars requires large observational studies with long-term follow-up in IBD patients. These studies should be supplemented by registries supported by manufacturers, healthcare providers, and patient associations, and traceability should be based on a robust pharmacovigilance system and the manufacturing risk management plan. ECCO’s statement also notes that although switching from the originator to a biosimilar in patients with IBD is acceptable, scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.

Switching from originator to a biosimilar should be performed following an appropriate discussion among physicians, nurses, pharmacists, and patients, and be done according to national recommendations. In particular, ECCO notes that the IBD nurse can play a key role in communicating the importance and equivalence of biosimilar therapy.

Danese S, Fiorino G, Raine T, et al. European Crohn’s and Colitis Organization [ECCO] position statement on the use of biosimilars for inflammatory bowel disease—an update. 