“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.
Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.
“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”
Concerns about safety
But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.
“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”
“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”
The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.
Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.
While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.
“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.
“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.
“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.
Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.