Regulator Explains How Denmark Has Achieved Its Biosimilar Success

Among European nations, Denmark has been a standout in terms of its biosimilar uptake and the cost savings achieved. During the first day of the BioTech Pharma third annual Biosimilars and Biologics Summit, held March 21 to 22 in Porto, Portugal, Nikolai C. Brun, MD, PhD, chief medical officer and director of the division of medical evaluation and biostatistics at the Danish Medicines Agency, shared how his national agency has actively worked to adopt and benefit from biosimilars, and provided a clear reminder of the fact that biosimilar uptake does not occur without concerted effort on the part of stakeholders.

Brun explained that Denmark has undertaken “one of the most radical” programs of biosimilar switching in the world. “Even countries that we normally compare ourselves to are left behind” in terms of the scale of Denmark’s biosimilar switching initiatives.

He reminded the audience that, while in the United States, interchangeability is a legal matter that governs automatic substitution at the pharmacy level, in the EU, interchangeability, which is governed at a national level, is a medical issue that relates to the ability to switch among products.

In Denmark, said Brun, there is a de-emphasis on clinical studies that demonstrate switching between biosimilars and reference products, and instead, the emphasis is on manufacturing processes and validation that the compounds are the same; “In Europe, we believe that if you’ve proven biosimilarity, you can switch, given that the price is good.” In Denmark in particular, if the EMA has deemed products to be biosimilar, “you can switch between the products any way you want.”

A key part of the Danish success with biosimilars involves the centralized system under which the country conducts its winner-take-all tendering process. “They have been able to negotiate some tremendous rebates,” said Brun, under this system in which price negotiations are conducted after both cost and budget impact analyses are completed.

Another crucial feature of Denmark’s success with biosimilars is the fact that patients are not given a choice regarding a switch. “We’re simply not purchasing the drug that loses the tender,” said Brun, so all patients who are receiving a given therapy must switch when the tender winner changes, with the exception of a very small number of patients who may have extenuating circumstances (such as cognitive issues that could make a switch untenable). While patients who have a loss of efficacy after a switch can switch back to the originator, usually after at least 3 months, everyone must try the switch, which typically begins just 12 weeks after the European Commission authorizes a biosimilar.

The lack of patient choice has not, however, proven to be a difficulty for Denmark. According to Brun, the national view on biosimilars among politicians, patients, doctors, and authorities is positive; it has been clearly communicated to stakeholders, he said, that only safe and effective drugs are introduced into the health system. When biosimilars were new to Denmark, he acknowledged, “there was noise” from some with ties to industry, but “we do not hear that noise anymore” after undertaking a strategy of transparency with patients. “It comes down to trust,” he said.

Building that trust has a great deal to do with a policy of ensuring that patients can access the same data that regulators can; part of the Danish transparency effort is the fact that, for 2 years after a biosimilar enters the Danish market, both the originator and biosimilar products are subject to surveillance as a legal requirement to facilitate a comparison between the biosimilar and the reference. Batch numbers are used for traceability.

Brun presented a case study of biosimilar etanercept, Benepali, to which patients receiving the reference, Enbrel, were switched in the first quarter of 2016. After 2 years of surveillance, there were only 3 reports of loss of efficacy after the switch. Two patients were switched back to the reference, and 1 patient regained efficacy. There were 23 reports of adverse events (AEs) with the reference, 22 reports of AEs with the biosimilar, and 6 reports that were unknown.

Similar results were seen with infliximab, when a switch commenced in the first quarter of 2015 from the reference Remicade to the biosimilar Remsima (sold in the United States as Inflectra). During the 2-year mandated reporting period, when 98% of patients had been switched to the biosimilar, there were 2 patients who reported loss of efficacy related to the switch.

Brun emphasized the fact that the Danish data are not from a randomized controlled trial, but instead are the results of systematic observation over years of the effects of switches. But these data, he said, are “important information that only a regulator can gather,” and they have been crucial in earning patients’ trust.

“In this case, we have switched [patients] very hard, said Brun, but a key to biosimilar acceptance is in the fact that “we have done due diligence.”