The biosimilars are coming: Tackling uncertainty and interchangeability
Part 2 of a 2-part series on biosimilars and the 351(k) pathway
The EU and India have a nearly decade-long head start on the U.S. when it comes to biosimilars. The reason? Both regions have had abbreviated and relatively well-defined pathways for biosimilar approval since 2006. So even though Sandoz only recently filed for Zarzio’s approval in the US, it has already been used for years in more than 40 countries.
As a result, Sandoz has Zarzio data spanning the equivalent of more than six million patient-exposure days. Upwards of 100,000 people have been treated with Zarzio since its introduction in 2009 -- including patients who may not have had access to the drug Zarzio emulates, Amgen’s branded Neupogen, and needed a more affordable treatment option. In 2013, Zarzio crossed a major milestone and became the first biosimilar to outsell its reference product.
A question of cost
Some experts argue that biosimilars will not be appreciably less expensive than brand-name biologics because of their high development costs. Healthcare data company IMS Health estimates that the cost of developing a biosimilar ranges from $100 million to $250 million – a far cry from the $1 million to $4 million necessary for small-molecule drug development.
But the numbers coming in from Europe tell a different story. In the EU, biosimilars are roughly 30% cheaper than their branded counterparts. And these cost-savings are likely to be seen in the US, too, with some in the industry asserting that prices could be as low as half the cost of originator products. In fact, Express Scripts projects that the US could save $250 billion between 2014 and 2024 if Zarzio and 10 other biosimilars are approved.
Biosimilarity vs. interchangeability
Resistance from brand-name biologics manufacturers notwithstanding, companies like Sandoz and Boehringer Ingelheim are ready -- and willing -- to jump into the biosimilar fray. But there are still significant hurdles in the approval pathway that need to be addressed.
One existential hurdle -- defining biosimilarity itself -- was recently addressed by FDA guidance which categorizes biosimilars into four basic categories: “not similar;” “similar” (requires additional evidence in order to be considered for approval); “highly similar” (potentially approvable); and “highly similar with a fingerprint-like similarity” (a.k.a. the gold standard).
The other major issue -- defining substitutability, also known as interchangeability -- is a bit trickier. But it is also critical to develop a working definition for it. As the Generic Pharmaceutical Association (GPhA) puts it, “Interchangeability is the engine that drives generic competition.”
As the term suggests, interchangeability centers on a drug’s capacity to be used in lieu of another drug -- i.e., if a physician writes a prescription for a brand name product, a pharmacy can substitute it with the biosimilar and rest assured that the therapies are pharmacologically comparable.
But creating such a universal standard is easier said than done. Defining true interchangeability of a biosimilar versus an original biologic product requires a far greater understanding of the biochemical processes that are used to generate biologics and their biosimilar counterparts than is currently available. To put it bluntly, we are smack dab in the middle of the learning curve on this issue.
Many groups, including GPhA and the Biotechnology Industry Organization (BIO), are pushing hard for legislation to create a pathway specifically for the substation of interchangeable biosimilars. Crucially, the FDA has also expressed an interest in moving such a pathway forward.
“The [Affordable Care Act] expressly states that a pharmacist or other dispenser may substitute an interchangeable biological product for the reference product without consulting the presiding doctor,” said FDA Commissioner Margaret Hamburg in remarks at the 2013 GPhA annual conference. “This is important. Substitutability helped spur the growth of the generic drug industry at an earlier time and is similarly essential to help foster competition in the biological drug market.”
The wave of the future
The world at large and America specifically is, undeniably, headed for a future in which biosimilars play a major role in the healthcare system. Sandoz alone has seven phase III clinical trials for biosimilar drugs currently underway.
But the road there is bound to be a bumpy one. The FDA will surely get better at clarifying issues surrounding interchangeability and making the 351(k) pathway easier to navigate as it develops a track record of reviewing and approving biosimilars. For the time being, the stakes are high for everybody involved.
You can read Part 1 of this series -- The Biosimilars Are Coming: Why Basaglar and Zarzio Are Harbingers of a New Pharma Landscape -- here.