Bertrand Liang of Pfenex addresses the state of the biosimilars industry, including key policy and drug pricing issues.

Biosimilars continue to gain momentum in the U.S. To date, two biosimilars have been approved in the U.S., with many more in production and going through clinical trials.

“Two biosimilars have been approved, both with full extrapolation across all indications of the reference product (for which there was not existing exclusivity), demonstrating the U.S. Food and Drug Administration (FDA) is experienced and comfortable with the 351 (k) approval pathway,” said Bertrand Liang, M.D., Ph.D., M.B.A., Founding Chief Executive Officer (CEO) of Pfenex and Chair of the Generic Pharmaceutical Association Biosimilars Council.

But, as we know, biosimilars are not new to the pharmaceutical industry—only to the U.S. pharmaceutical market as of 2015. With this youthful emergence, many industry experts and consumers yet remain in the dark as to what biosimilars truly are. According to a survey by PricewaterhouseCoopers (PwC), 67 percent of consumers do not know what a biosimilar is.

Despite this, the biosimilars market continues to possess a significant amount of potential—namely that of changing the landscape of the biopharmaceutical market.

“Data from RAND Corporation and Express Scripts reveals that projected savings from biosimilars in the U.S. could range between $44 billion to $250 billion over the 10 years spanning 2014 to 2024,1,2” said Liang. “With the dollar amount of biologic patents set to expire by 2020, we anticipate an increase in the number of biosimilars approved in the U.S. in the coming years.3

Biosimilars Around the Globe

Unlike the U.S., biosimilars aren’t new to countries such as Europe and India.

“Europe is celebrating 10 years of experience and more than 400 million patient days of safe and effective treatment using biosimilar products since the first biosimilar was approved and marketed in 2006,4” said Liang. “Europe currently has more than 20 biosimilar medications approved with requisite increased patient access.5 For example, since the introduction of biosimilar filgrastim in the UK, about double the number of patients have been able to receive this life-saving drug than before the advent of biosimilars.4

India has been utilizing biosimilars since 2000 and has more than 25 approved biosimilars today.6

In addition to Europe and India, Australia currently has 11 approvals and Japan currently has seven.7,8

“Biosimilars are relatively new to the U.S. in comparison to these geographies, having been ushered in when Congress enacted the Biologic Price Competition and Innovation Act (BPCIA) in 2010. Since then, FDA has released a number of guidance documents to help clarify this pathway in the U.S.,” said Liang.

What’s on the Horizon for Biosimilars

“In the U.S., we anticipate seeing the rate of biosimilar approvals increase in the coming years as patents for blockbuster biologics expire,” said Liang.

Approximately $71 billion of biologic patent exclusivity in the U.S. is expected to expire by 2020, according to IMS Health.3

“As the market grows, we anticipate increased uptake of biosimilars in the U.S. and across the world as providers and patients experience the cost-savings and increased access they can provide,” said Liang. “For example, a survey by the European Crohn’s and Colitis Organization found that 44 percent of physicians surveyed consider biosimilar infliximab interchangeable with the reference product, compared to only 6 percent feeling that way in 2013.8 Furthermore, in the U.S., the evolution of the regulatory pathway should include the release of draft guidance documents around interchangeability as well as statistical approaches by the end of this year.”

U.S. Biosimilars Market Trends

“The biosimilars market is nascent, given that only one product is being marketed, although the other product which has been approved certainly is anticipated to be launched sometime soon,” said Liang. “However, there are at least a couple of areas we see becoming apparent.”

At the biosimilar panel at the most recent Generic Pharmaceutical Association meeting, Brian Lehman from OPERS said he expected that his organization would have tiers just for biosimilars—given the overall savings and increased access these medications are likely to afford patients.

The marketplace is also likely to be affected by policies which will tackle the high costs of biopharmaceuticals—and biosimilars are likely to take a center stage as part of the solution to this problem.

Biosimilars are priced differently in different countries. In some countries, there is a tender system, while others there is a mix of reimbursement components including state and/or provincial resources.

“The state of pricing in the U.S. will depend on the reimbursement schema, whether by the federal government, and the component pricing mechanism thereof (Medicaid, Medicare, 340B etc.), or private third party payers,” explained Liang.

Liang said that they are hopeful that policies allowing for even-handed competition will arise and be supported to help mature the “fledgling market.”

Biosimilar Interchangeability, Naming, and Coding

“Current key biosimilar policy and regulatory issues in the U.S. have to do with interchangeability, naming, and coding,” said Liang. “Interchangeability refers to the substitution of a biologic with a biosimilar at the pharmacy level.”

In addition to meeting the biosimilarity standard, an interchangeable biosimilar is expected to produce the same clinical result as the reference product in any given patient.

“Thus, within the definition of interchangeability, for a product that is given to a patient more than once, the risks associated with safety and efficacy when alternating or switching between the interchangeable and the reference product is not greater than that associated with administration of the reference product,” Liang explained.

A number of states have passed laws allowing for substitution of interchangeable biosimilars consistent with the pharmacy practice around such substitution seen with, for example, generic drugs. This stance, according to Liang, treats an interchangeable biosimilar and the corresponding reference product the same when it comes to pharmacy dispensing.

“The FDA expects to publish guidance for industry around interchangeability this year," said Liang. "Many states have already passed legislation permitting biosimilar substitution at the pharmacy for biosimilars that have been deemed interchangeable by the FDA.11 The industry is looking forward to long-awaited interchangeability guidance."

Last year, the U.S. FDA and WHO released proposals for naming biosimilars that “advocate the addition of ‘qualifiers’ to the International Nonproprietary Name (INN) to distinguish the medication as biosimilar” Liang explained.

“We do not believe that there is a need for any such qualifier and that it might create confusion among providers and administrators. In Europe, the INN has been used for biosimilars without any type of modifier for 10 years, and there have been no issues with safety or traceability,” said Liang.

Another area for improvement has to do with changes to the Healthcare Common Procedure Coding System (HCPCS) that the Centers for Medicare and Medicaid Services (CMS) announced in 2015.

“The changes required all biosimilars of a particular reference product to have the same J-code, and one that is different from that of the reference product as it relates to Medicare Part B reimbursement,” said Liang. “Because biosimilars are developed in comparison to a reference product, rather than to other biosimilars, it makes little scientific sense to blend all biosimilars into the same J-code, as opposed to having either independent codes or codes shared with the reference product to which the biosimilar was compared. Linking reimbursement to other molecular entities to which the biosimilar was not initially compared does not make sense.”

Going Forward

“The key issues and drivers behind the biosimilars market in the U.S. relate to solidifying the policy and regulatory environment that expedite the development of a robust and competitive market,” said Liang. “In order to further support the development of the biosimilars market, there must be a concerted effort toward the education of providers, patients, payers, and policy makers as to the safety and efficacy of biosimilars.

“The FDA has begun this effort, targeting physicians—having recently launched an online Continuing Education course for physicians to learn about biosimilars. We anticipate seeing more education from the FDA and industry expanded to additional audiences going forward.”

  1. RAND Corporation, “The Cost Savings Potential of Biosimilar Drugs in the United States,” by Andrew W. Mulcahy, Zachary Predmore, Soeren Mattke. Nov. 3, 2014.
  2. Express Scripts, “The $250 Billion Potential of Biosimilars,” by Steve Miller, MD. Apr. 23, 2013.
  3. Presentation, “The Business of Biosimilars,” by Doug Long, Vice President, Industry Relations, IMS Health, March 2015, p. 8. Source: IMS Midas, 06/2014, Rx bound, IMS Patent focus.
  4. Medicines for Europe, “Biosimilar Medicines: Did You Know?” Accessed Apr. 2016.
  5. Generics and Biosimilars Initiative, “Biosimilars Approved in Europe,” updated Feb. 5, 2016.
  6. Generics and Biosimilars Initiative, “'Similar Biologics’ Approved and Marketed in India,” updated Apr. 22, 2016.
  7. Generics and Biosimilars Initiative, “Biosimilars Approved in Australia,” updated Feb. 5, 2016.
  8. Generics and Biosimilars Initiative, “Biosimilars Approved in Japan,” updated Apr. 22, 2016.
  9. European Crohn’s and Colitis Organisation, “P312 Has IBD specialists’ awareness of biosimilar monoclonal antibodies changed? Results from a survey amongst ECCO members,” by S. Danese, G. Fiorino, and P. Michetti. Accessed Apr. 2016.
  10. IMS Health, “Medicines Use and Spending in the U.S.: A Review of 2015 and Outlook to 2020,” by IMS Institute for Healthcare Informatics. Apr. 14, 2016.
  11. Generic Pharmaceutical Association, “GPhA and Biosimilars Council Praise New State Laws to Allow Automatic Substitution for Interchangeable Biologics,” May 13, 2015.

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