Thursday, October 18, 2007

Biosimilars in Europe: Docs Decide

Biosimilars may have won a regulatory pathway in Europe, but they’re having a tough time getting to patients. Last week Spain became the second of Europe’s big five markets, after France, to announce this year that biologic drugs cannot automatically be substituted. Italy is expected to announce a similar decision before year-end.

In many European countries, pharmacists are required—sometimes incented—to dispense a cheaper generic equivalent of whatever brand a doctor has prescribed, if one is available. The rulings in Spain and France mean that this principle won’t hold for biologic drugs—a category for which substitution rules have not, until the advent of biosimilars, been needed at all.

It’s a blow for biosimilar firms, banking on their products’ lower price and perceived equivalence to reference biologicals in order to gain market share.

Doctors will henceforth have to specify which precise brand they want to dispense; if they don’t, “pharmacists will have to check back with the doctor,” according to Thomas Bols, Chair of EuropaBio’s Biosimilar Working Group and Director, Government Affairs, Amgen.

Now granted, for most biologicals we’re talking hospital docs, working in a specialized setting. But the situation still sounds somewhat complex, particularly given biosimilar firms’ apparent victory when Sandoz’s EPO was granted the same international non-proprietary (INN) name as its reference drug, J&J’s Eprex. (Both are epoetin alfa, and you can read more here.)

Same non-proprietary name, same drug, right? Wrong. Bols admits that this particular INN decision from the World Health Organization (in charge of INN naming), came as a surprise to the innovator lobby. But, he adds, any lingering questions over the appropriateness and enforceability of INN rules “only emphasize the need for good rules on automatic substitution.”

For him, a good rule is what’s emerged in France and Spain, as well as in the Netherlands and some Nordic countries: placing the onus on doctors to explicitly prescribe the generic. That means docs need to understand both sides’ arguments. Fine for the innovators—marketing is a big part of what they do. Not so fine for generics firms, for which marketing falls outside of their strategic and financial scope.

Now granted, in countries like Germany, doctors too are incented by budgetary restrictions to prescribe cheap drugs where possible. Similar cost-pressures apply in hospitals. But all doctors also hear innovator lobbyists emphasizing that “approval [of biosimilars] is based on a limited safety package,” as Bols clarified to IN VIVO Blog, and that there are “important therapeutic differences” between biosimilars and innovator drugs. What doctor is going to prescribe a biosimilar for which there’s little or no on-market experience, rather than a branded drug, in particular for chronic conditions?

The European Generics Association, representing biosimilar firms, calls all this scare tactics. According to Suzette Kox, the EGA’s Senior Director of Scientific Affairs, the Spanish decision “won’t impact [doctors’] prescription of biosimilar medicines” but “raises concerns because it is based on perceptions created by certain interested parties, and on a lack of scientific information and knowledge.” She argues, as EGA has all along, that manufacturing changes to any reference drug—a new plant, a new cell line or whatever—introduce variability within innovator products that’s analogous to that between an innovator drug and a biosimilar, yet all batches of innovator drugs like Eprex are assumed to be interchangeable. “The same scientific approach should apply to biosimilar medicines,” she asserts, “as there is no fundamental difference between biosimilar and their respective reference products.”

Some docs will believe that; some, too, might read the EMEA guidelines which state that trials of biosimilar medicines are required to demonstrate that there are “no meaningful differences between the biosimilar and the biological reference medicine in terms of safety or efficacy” before approval is granted.

The fact is that no-one really knows just how similar biosimilars are to reference drugs, and they won’t know until such products have had several years’ worth of market exposure. That’s why the question of how often and how widely these drugs should be prescribed is being passed like a hot potato: EMEA left the substitution decision up to member states, and governments have now passed it on to doctors.

That’s not, fundamentally, a bad situation: why shouldn’t prescribers decide? Brand-specific prescribing also makes pharmacovigilance easier; indeed, this is a key argument that innovators put forward in favor of the approach.

Once such pharmacovigilance data is available, splattered all over the web and in cost-conscious health ministries’ hands, it’s possible—granted no nasty surprises--that some of these rulings on non-substitution may be reversed. (And maybe by then the US will pass biosimilars legislation, too.)
In the meantime, though, biosimilars will be treated with caution--short of any radical new government cost-cutting measures that speak louder to docs’ pockets than clinical scare stories do to their scientific judgment.

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