Boosting biosimilar uptake in the US: what needs to change?

There are several key regulatory differences between the US and Europe that have helped to create the disparity in their respective biosimilar experiences. On the simplest level, the European Medicines Agency (EMA) was much faster to define a biosimilars pathway and provide guidance on their development.

EMA’s biosimilar guideline was in place in 2005, setting the stage for Europe’s first biosimilar approval of Sandoz’s recombinant human growth hormone Omnitrope in 2006. In the US, meanwhile, a firm guideline didn’t appear until 2009-2010 with the introduction of the BPCIA. This slower pace, coupled with biosimilars getting bogged down in the FDA approvals process, meant the approval of the US’s first biosimilar, Zarxio, took until 2015 to materialise.

“There has been a lot of interest and a lot of anticipation of the development of the [US] biosimilars market; it hasn’t occurred as quickly as many of us would like,” says Christine Simmon, executive director of US trade group The Biosimilars Council.

Another crucial point of divergence between the US and Europe is their stances on biosimilar interchangeability, which vary dramatically. In Europe, the EMA provides a biosimilar approval, with national medicines authorities providing guidance on interchangeability to prescribing physicians who may decide to switch patients on to a biosimilar.

“It’s relatively straightforward and it gives doctors comfort to make that kind of switch,” says van den Hoven. “I think that was the best approach because these are very complex drugs, often injectable drugs, so therefore there’s a lot of physician involvement in these processes.”

The FDA has taken a more cautious approach, and one that may have hampered the development of its biosimilar market. The US ‘interchangeable’ designation is separate from the basic biosimilar approval, and requires the substitution of a biologic drug for its biosimilar counterpart at the pharmacy level, without prescriber involvement. Although 38 of 50 US states have now passed legislation to support biosimilar substitution in pharmacies, van den Hoven argues that the whole substitution debate is premature at a time when – even now – no fully interchangeable biosimilar has been approved in the US.

Beyond regulation, the complexities of the US payer system and the actions taken by pharma companies to block competition to their originator biologics have put biosimilars at a disadvantage in the market. Biologic manufacturers often offer massive rebates on originator products to undercut biosimilar competition, setting an almost impossible barrier to market entry – a move that would likely set off a competition investigation in Europe, but which seems to fall into a grey area in the US.

“Once biosimilar makers see that the system is rigged against them, what’s the incentive for a biosimilar maker to pour money into future investments to develop these lower cost alternatives?” asked FDA commissioner Dr Scott Gottlieb during a speech in March.

“Biosimilar utilisation may unfortunately be disincentivised due to the rebating and reimbursement structures of the payer system,” says Simmon. “You see current litigation with Pfizer and J&J in the courts battling over the rebate agreements in the private contracts with others in the supply chain, preventing the uptake of Pfizer’s version of Remicade. That is a concern.”

Many approved biosimilars are locked in patent litigation disputes, further slowing down the market and scaring off potential new entrants. “They are facing so many patents, some of which would perhaps be viewed as deliberately fought in order to thwart competition, maybe without merit,” Simmon adds.

Other market issues tie back into regulation; the fact that no biosimilar is currently approved as interchangeable by the US definition has prompted payers to place them on non-preferred tiers, further disincentivising their use, says Dharmarajan.

Given these disadvantages and the huge potential impact that biosimilars could have on US healthcare costs, what needs to be done to turn the situation around? From a regulatory perspective, FDA’s interchangeability requirements could be relaxed and a more prescriber-driven system adopted to encourage biosimilar uptake. The approval pathway could potentially also be accelerated with the use of real-world safety evidence from Europe, as long as post-marketing follow-up studies are conducted to catch any unexpected adverse events.

“One thing the FDA could consider is accepting real-world evidence about safety and efficacy from Europe,” Dharmarajan says. “Some of these biosimilars have already been on the market and physicians are fairly confident about them.”

Pharma market reform could also help boost biosimilar adoption and shield this developing market from unfair practices. The Biosimilar Council is lobbying in favour of the CREATES Act, which would make it harder for pharma companies to delay generic and biosimilar competition through, for example, denying access to reference product samples.

Dharmarajan isn’t expecting to see major regulatory changes until 2019 or 2020, but Simmon is hopeful that FDA guidance and reforms such as accepting EU safety data will be coming soon, especially in light of Gottlieb’s more proactive stance.