Biosimilars: Dead Before They Really Got Started?

That was a conclusion that it was possible -- even feasible -- to draw after listening to several of the sessions at the European Generics Association's International Symposium on Biosimilar Medicines in London last week.

Most overtly, it was a suggestion by Alan Sheppard, Principal and generics expert at IMS Health. After showering the audience with numbers, he concluded -- albeit with the caveat that this was his personal view, not IMS'-- that, "as we move towards modified biologics, it may be nearly the end for biosimilars already."

You'd think that with billions of dollars' worth of patent expiries happening now or due before the end of 2012 and the rash of austerity drives by payers across the globe, it would be biosimilars' hey-day. They're copies of those most expensive biologics, after all. And those biologies are what's helping push the global drugs bill up and up -- by about $50 billion each year.

But no. Global biosimilar sales might have doubled each year since 2007, but the global market was still worth only $235 million in mid-2010, according to IMS. And in the one example of a biosimilar capturing decent (60%) market share, EPO in Germany, "it looks as if penetration may be slowing off," Sheppard ventured. Meanwhile, biosimilar growth hormone in Germany just hasn't happened: with less than 4% market share, it has been a failure.

"If I'm absolutely honest, people are disappointed," admitted a former senior executive at Teva during coffee.

Some of the problems are well-known. Lack of interchangeability is probably the most significant: if pharmacists can't automatically substitute an originator drug with a biosimilar, it means doctors need to actively prescribe biosimilars. Most don't feel confident doing so. "At the moment, biosimilars create uncertainty in the doctor's office. Innovator drugs offer a solution. Biosimilars don't have that clear advantage, and actually, they may carry some unknown risk," given the limited trial results supporting their use, relative to that of the innovator drug. That was the view of Arnold Vulto, a practicing pharmacists and Deputy Head Hospital Pharmacy at Erasmus University Medical Center in Rotterdam, Holland.

His point: doctors need reliable and accessible information, particularly around proof of bioequivalence, to change their minds. That information is missing, for now.

Meanwhile, originators have got their act together and are busy launching life-cycle managed enhancements to their drugs -- new delivery pens or longer-acting versions.

They're also enjoying biosimilars' effective lock-out of the US, where the regulatory pathway remains unusable, Sanford Berstein analyst Ronny Gal reminded the audience in London. That' because it's so easy for originators to sue hapless biosimilar firms for infringement, thus blocking approval for up to 42 months -- however shaky the infringement claim may be.

And Europe hasn't escaped the lawsuits either: Norway, a land of low drug prices, embraced biosimilars enthusiastically, adding biosimilar filgrastim to its automatic substitution list in mid-2010. The country's health department had, via a hospital tender system, secured a price for the biosimilar copy that was less than a third of that of the original, Amgen's Neupogen. But Amgen sued -- and was successful, in part because the country's laws aren't sufficiently up to date, according to Steinar Madsen, Medical Director at the Norwegian Medicines Agency. The health department will shortly decide whether to appeal the decision.

Madsen reported that Norway's doctors -- like those elsewhere across Europe -- want to see interchangeability studies, proving the drugs' safety even through several switches backwards and forwards, and robust pharmacovigilance tracking systems. New European-wide pharmacovigilance legislation will help a bit.

But fundamentally, said Madsen -- a doctor himself -- the only way to increase biosimilars' market share is reduce the influence of doctors, and allow insurers to tender for the cheapest drugs and ensure they are used from the start of treatment. "EMA should modify their position that choice [of treatment] should be left to the doctor," he declared.

That's hardly likely. But all is not lost. The generics proponents are waiting for the next, they say far more valuable chapter in biosimilars' short history: antibodies. "Biosimilar antibodies have far more potential than this first round of drugs," the former Teva executive told The In Vivo Blog. They'll go into less competitive markets than the likes of growth hormone, GCSF and EPO, and will thus support higher prices," he said.

Given their complexity, mAb lookalikes are hardly going to coast past the regulators, though, nor past those uncertain doctors seeking a reason to prescribe. Still, the tough reality of health care economics -- plus the commitment of large players like Teva, Sandoz and Merck, who continue to invest despite the challenges -- mean we haven't seen the last of biosimilars yet.

image by flikrer TuTuWoN used under creative commons