What You Need To Know To Launch Biosimilars Globally

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

As the U.S. makes progress on its own unique biosimilar regulatory path, I’ve become increasingly interested in how other countries are approaching biosimilar policies and development in general. I’ve written a few articles focused specifically on tackling emerging market regulatory pathways, many of which have slight differences from each other. And just last week, I published an article discussing how Europe has approached biosimilar naming and switching. But I found myself particularly surprised by some of the country-level insights I gleaned from Suzette Kox, senior director of the Biosimilars Medicines Group and chair of the biosimilars committee of the International Generic and Biosimilar Medicines Association. In her speech at the GPhA Biosimilars Council Leading on Biosimilars Conference, Kox laid out the unique regulatory frameworks in several countries, highlighting the challenges facing companies planning to launch products globally. 

Impact Of Real-World Data, Physicians On Biosimilar Switching

Real-world data is getting a lot of buzz in the biosimilar industry. And rightfully so. It sometimes feels as though new studies relevant to the biosimilar space are released daily. For instance, results from the highly anticipated NOR-SWITCH study were announced a few weeks ago. And just this week, two more publications came to light, one revealing the level of biosimilar awareness of U.S. specialty physicians, and the other discussing the role and safety of biosimilars in the oncology space. 

The increasing amount of positive data surrounding biosimilar use has encouraged international regulators to launch new policies or amend older policies. Take switching, for example, in which a patient is switched from the biologic to the biosimilar by their doctor. Kox pointed out there have been three countries — Holland, Finland, and Germany — that have become particularly proactive in encouraging the use of biosimilars in place of reference products. But not all of these countries were originally open to the concept of switching. “Two years ago, Holland believed biosimilars should only be prescribed to naïve patients,” she described. “Now based on the data, real-world evidence, and the experience within the country, they have altered their position.” In addition, France, Italy, Belgium, Portugal, and other countries are working on revisions to their switching policies, as well as striving to bolster harmonization among regulators.

The payer’s role in ramping up biosimilar use also continues to be a hot topic of discussion in the U.S., as several key payers recently prioritized biosimilars on their 2017 formularies. Abroad, Norway and Denmark are often hailed as key examples of successful payer-based switching because hospital tenders have sparked rapid biosimilar uptake. However, according to Kox, this isn’t an accurate model of payer-based uptake. “The doctors in these countries are in the driver’s seat,” she stated.

The IMS Institute for Healthcare Informatics report released earlier this year discussed the important role physicians play in the Norwegian Drug Procurement Cooperation (known as LIS), which organizes procurement for the hospital tender. The panel evaluating the drugs for the tender primarily comprises physicians. These experts determine which drugs to place on the tender based on clinical- and cost-related factors. Naturally, this results in greater trust and confidence from physicians, which is, obviously, an important factor for all markets. Kox stated, “A multi-stakeholder approach is important for building confidence in biosimilars from the start. Doctors must be in the loop, because they will react negatively when they have not been part of the decision making process.”

A Glance At Global Biosimilar Markets

Though it really goes without saying, there are clearly many regulators, regulations, and data requirements facing biosimilar makers. A topic Kox touched on briefly was international convergence efforts. At the DIA conference at the end of October, it was clear global regulators are dedicated to uniting efforts to streamline development requirements for biosimilar makers. But the following markets reveal some of the interesting differentiations in policy or market dynamics that companies will likely come across as they consider expanding their biosimilar programs.  

• Australia earned its spot on biosimilar makers’ radars when its Pharmaceutical Benefits Advisory Committee (PBAC) came out in support of substitution at the pharmacy level without the doctor’s involvement. This process, known as ‘a-flagging,’ is currently recommended by the PBAC for infliximab, insulin glargine (though, with some controversy), and, most recently, etanercept. But what is most interesting to note is that ‘a-flagging’ has had little to no impact on biosimilar uptake. For infliximab in particular, the drug has only garnered 2 percent market share after six months — regardless of its ‘a-flagged’ status. Though Kox did not offer reasons for this slow uptake, it’s important to note doctors and patients are able to request brand-name treatments only. It’s likely Australia’s slow uptake stems from overall caution about biosimilars, which is being observed in a majority of markets. Australia has dedicated $20 million to launch a biosimilars awareness campaign, though progress with that is also slow. There seem to be some contradictory methods of addressing the slow uptake. For instance, there have been recommendations the country should only start naïve patients on the biosimilar, as well as calls for lower co-payments to incentivize use.

 

• Canada became known for its decision to not grant extrapolation to gastrointestinal indications for the first infliximab biosimilar. The regulator has since amended this decision following the review of additional data. Perhaps one of the biggest challenges facing biosimilar companies approaching Canada is the lack of transparency over deals with innovators to use the reference products. “Many private payers have nontransparent listing agreements with the originators, in turn negatively impacting biosimilar uptake,” explained Kox. (I plan to cover the regulatory landscape of Canada more thoroughly in an upcoming article, so stay tuned.)

 

• Japan: By Cox’s count, there are seven or eight biosimilars on the Japanese market, and biosimilars have brought in around $89 million in sales. In the past, the country has emphasized a more local approach to drug development and treatment, prioritizing Japanese patients, products, and Japanese-sourced reference products. But this has begun to shift. According to Kox, “Japan has agreed, like the U.S. and EU, to accept a non-Japanese sourced reference product in comparability exercises, provided this reference product is representative of the biologic approved and marketed in Japan.” The country also boasts a different naming strategy than we’ve seen in the U.S. or Europe. Biosimilars must have a suffix of the company name, followed by BS (for biosimilar) and the number 1, 2, or 3, which designates the order of approval. (Kox said it best: this policy is “not very sexy.”)

 

• In Mexico, biosimilars are known as “biocomparables/biocomparable products.” This is because the term “similares” is connected to small molecule products on the market which are regarded negatively. (Interesting to note, Europe considered using the term “biocomparable product” between 2001 and 2005 as the nation approached the approval of its first biosimilar in 2006.) Kox also introduced the term “biolimbos,” which describes biosimilar products in Mexico that have not been subject to a review which embodies the global standards for biosimilar approval. The regulatory pathway for biosimilars in Mexico was established in 2012, but it did not take effect until 2015. As such, manufacturers that have launched “biolimbos” are expected to carry out the necessary tests to meet the safety, efficacy, and quality standards and reapply for approval of their products as biosimilars.