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Can Pharma Learn To Stop Worrying And Love Biosimilars?

This article is more than 8 years old.

Another important milestone in the evolution of the biosimilars market appears close. Earlier this week, an FDA advisory committee overwhelmingly recommended approval of CT-P13, a biosimilar version of Johnson & Johnson's TNF-inhibitor Remicade developed by the Korean biotech Celltrion . Assuming the agency follows recommendation of the AdCom, it will be marketed in the U.S. by Pfizer , which obtained marketing rights via its acquisition of Hospira last year. Furthermore, AdCom recommendation extends to extrapolation of all seven indications for which Remicade is approved (recognizing orphan exclusivity will apply to one), based on Celltrion's study data in just two of these indications.

Based on the precedent it set last year in approving Novartis' Zarxio (biosimilar filgrastim), the FDA can be expected to approve the second U.S. biosimilar--and the first biosimilar monoclonal antibody--within the next few months. As Bernstein analyst Ronny Gal suggested in a note to investors last week, the biosimilars pathway works. In addition, unlike Zarxio--a "rather simple protein, supported by near perfect data, multiple years of EU experience and a brand-name sponsor, CT-P13 is a complex monoclonal antibody, with an open question on at least some of the data, modest EU experience and sponsored by a company without a single product on the U.S. market."

Furthermore, "the FDA was far more emphatic in their support of CT-P13 during this advisory committee meeting," Gillian Woollett, FDA practice lead at Avalere told me this week. She added that "during the Zarxio meeting (in January 2015) they were more neutral in their discussion. This time the FDA was more active in clarifying why it had reached its conclusions."

If last week's AdCom has provided some clarity on one key question--extrapolated approval for monoclonal antibody biosimilars--the key outstanding issue is interchangeability; a designation the FDA has said it is willing to consider and grant for biosimilar products. This would have profound commercial implications, by encouraging greater use of a biosimilar among patients already established on the originator product.

It is important to note that at this point, neither Novartis or Celltrion have sought interchangeability status for Zarxio and CT-P13, although both companies have presented some switching data at their respective AdCom meetings, which could be used to support future applications. The FDA has indicated that it will publish guidance on interchangeability later this year, although it has been promising this for the past 24 months.

Woollett outlines a scenario which could keep branded pharma companies awake at night; while guidance is unlikely to be as detailed as many are expecting, she believes the FDA could approve an interchangeable biosimilar irrespective of when guidance is published. Citing manufacturing changes for originator biologics, which the FDA says result in versions of the product that are "interchangeable with themselves and have been recognised in the vast majority of cases without any clinical or switching studies," many of the concepts around biosimilar interchangeability are already well understood and routinely applied by the FDA, says Woollett. Remicade has undergone more than 37 such manufacturing changes since initial approval in 1998.

Similarly, the FDA requested Celltrion provide a single-switch analysis (presented at the AdCom) and concluded in its briefing documents that "the single transition from EU-approved Remicade to CT-P13 during the long-term extension studies in rheumatoid arthritis and ankylosing spondylitis did not result in worse safety or immunogenicity profile. This would support the safety of a clinical scenario where non-treatment-naïve patients undergo a single transition to CT-P13." There is speculation the agency may look to establish a category below full interchangeability, which would allow a single switch from brand to biosimilar and could theoretically be included in CT-P13's label. In a recent note to investors, analysts at BMO Capital Markets suggested that "payers care much more for a single transition from brand to biosimilar as opposed to interchangeability."

Rather than fight this threat--and for some companies (AbbVie, we are looking at you) the threat is more pronounced than for others--the branded pharmaceutical industry should embrace the opportunity offered by biosimilars, suggests Woollett. “After all, the same science applies to everyone.” She is not arguing that more originator companies should necessarily invest in biosimilars as Pfizer is doing; nore does she believe these players will deliver a greater return on biosimilars versus innovative drugs, and she argues that some companies that are active in the market still don’t fully appreciate the necessary level of investment. Instead, Woollett believes that a more proactive stance towards access to biosimilars would provide the industry a suitable conduit to tackle the growing pressure it faces over pricing and the value that drugs provide.

Severin Schwan--the CEO of Swiss pharmaceutical giant Roche--echoes this view; he told me in 2013 that biosimilars are part of the industry's "contract with society." Interestingly, biosimilars represent a notable threat to Roche in particular, given the high proportion of revenues it generates from the three oncology biologics Avastin, Herceptin and Rituxan. Nevertheless, Schwan has argued that it is in the company's interest for biosimilars to exist, "in order to ensure protection of the current model." Presciently, given the scrutiny that pharma is currently attracting, Schwan suggested in 2013 that perpetual ever-greening of expensive products would ultimately trigger a backlash from payers in the long term.

It should be noted that Roche has not stood down completely when it comes to the biosimilar threat. Illustrating the significance of interchangeability, the company has previously led efforts in the U.S. to push through state-level bills designed to limit, or at least raise the regulatory hurdles necessary to support biosimilar substitution with originator brands. However, Roche has pursued a "biosimilar defense" strategy centered primarily on the development of innovative new products that are designed to advance the treatment paradigm and reduce its exposure to biosimilar competition.

The successful approval and launch of Perjeta--for HER-2 positive breast cancer--is the best case example of this strategy to date. It has not proven perfect; Perjeta is used in combination with Herceptin and has not relegated the older therapy from the first- to second-line setting as Roche has hoped. With momentum for biosimilar antibodies accelerating, however, Roche's strategy appears well thought through and supplemented by its strong track record in "pulling R&D rabbits from the hat," notes Bernstein analyst Tim Anderson.

If its peers can follow a similar path, the advent of biosimilars in the U.S. may provide a good opportunity for the branded sector to placate politicians and the public as debate over drug prices continues.

Simon King is an Executive Editor at FirstWord Pharma PLUS.