Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
Norwegian Government-Funded Study Supports Switching Patients to Remicade Biosimilar
A trial funded by the Norwegian government has generated data to support switching from Johnson & Johnson’s Remicade to a biosimilar. Overall, participants with rheumatoid arthritis, Crohn’s disease and other conditions who switched to the biosimilar had comparable outcomes to patients who stayed on Remicade.
The study randomized 481 patients who were taking Remicade to either continue on the innovator biologic or switch to Celltrion’s CT-P13. After 52 weeks, the condition of 29.6% of participants in the CT-P13 cohort had worsened, compared to 26.2% in the Remicade arm. The difference between the two arms was not statistically significant. CT-P13 delivered comparable data to Remicade against a set of secondary endpoints, including incidence of anti-drug antibodies. The study team is claiming the safety profiles are comparable, too, although it has yet to post the data.
Armed with the data, the researchers concluded switching to CT-P13 was not inferior to continuing to take Remicade.
“The data shows that safety and efficacy are maintained post-switch and should give confidence to physicians looking to move their patients onto biosimilar infliximab for non-medical reasons such as cost,” Jørgen Jahnsen, a co-author of the study and professor of gastroenterology at the University of Oslo, said. “I am hopeful that switching will lead to financial savings that can in turn enable more patients to receive this life-changing medicine.”
The question, from a regulatory, healthcare and business perspective, is whether the finding can be used to support decisions about the interchangeability of Remicade and CT-P13 and, beyond that, extrapolated to other biosimilars. While the overall data were comparable, there was variability in the individual diseases studied. Among the 77 Crohn’s disease patients who switched to CT-P13, 36.5% experienced disease worsening. The condition of 21.2% of the 78 patients in the Remicade arm got worse over the course of the trial.
Even so, the data help to undermine one of the arguments Merck, which sells Remicade in Europe, has used to try and counter biosimilar competition in Norway. Orion Oyj has upended the market in Norway in recent years by offering its Remicade biosimilar at a discount of almost 70%. That resulted in many doctors switching to the biosimilar, turning Norway into a test case for the merits of moving stable patients from innovative biologics to copies. Merck fought back by noting the lack of evidence on the consequences of switching. The study begins to provide that evidence.
The accrual of evidence to support interchangeability has implications beyond Norway. Recently, the European Commission published a report on the fiscal sustainability of healthcare that called for more use of biosimilars. “Countries should seek ways to promote the availability of low price medicines, particularly of generics and biosimilars,” the authors wrote. “Pharmacies should be allowed to operate generic substitution, and biosimilars substitution under the supervision of a health care provider.”
Study Abstract, Press Release, EC Report
Italy Fines Aspen $5.7M for Increasing Cancer Drug Prices by up to 1,500%
The Italian Competition Authority (ICA) has fined Aspen $5.7 million for raising the prices of off-patent cancer drugs by up to 1,500%. Aspen bought the drugs from GlaxoSmithKline before going on to take a hard line in pricing negotiations with the Italian Medicines Agency (AIFA).
In a 96-page report, ICA accuses Aspen of adopting a negotiating position that amounted to a threat to disrupt the supply of the five products. As the sole supplier of the medicines, Aspen was in a strong position going into the negotiations and used this to seek price increases ranging from 257% to 1,540%. During this time, some of the drugs became hard for patients to find, prompting a consumer group and, later, the antitrust regulator to look into the matter.
This led to the 96-page report and the $5.7 million fine. ICA imposed the fine after concluding the prices charged by Aspen were out of proportion with the cost of making and marketing the drugs. Aspen never made much money from the drugs — ICA puts sales at approximately $5 million to $11 million — but officials chose a fine commensurate with the size of its organization, not just the aspect of its business being investigated.
ICA took the approach to setting the size of the fine in an attempt to ensure the penalty was an effective deterrent to Aspen and other companies which may be tempted to pursue similar pricing strategies.
Press Release, Antitrust Ruling (Italian)
UK Forges Biological Standardization Agreement with Korean Regulator
The UK National Institute of Biological Standards and Control (NIBSC) has signed a memorandum of understanding (MoU) with Korean regulators. NIBSC entered into the agreement with Korea’s National Institute of Food and Drug Safety Evaluation (NIFDS) to promote biological standardization.
Having formed the MoU, NIBSC and NIFDS plan to work together to promote the standardization of biologic medicines and diagnostics. Details of specific plans are yet to emerge, but potential activities include collaborative studies and work to optimize the processing and transportation of material.
The partners are also looking to set up joint workshops and other forums at which scientific experts can exchange ideas. NIBSC sees such initiatives building regulatory capabilities in the UK and Korea.
NIBSC is part of the UK Medicines and Healthcare Products Regulatory Agency.
Teva Thyroid Generic Returns to Market Four Years After Equivalence-Related Suspension
The Commission on Human Medicines (CHM) has cleared Teva to start selling levothyroxine tablets in the United Kingdom again. CHM triggered the withdrawal of the product in 2012 by calling for the suspension of its marketing authorization on the basis of evidence it was less effective than the reference drug.
Teva’s levothyroxine tablets were supposed to be comparable to those sold by another manufacturer. However, physicians reported reduced efficacy when switching patients from the reference product to Teva’s generic copy. When paired to manufacturing issues, CHM felt these reports were serious enough to warrant recommending the suspension of Teva’s levothyroxine. Now, almost five years after CHM made its original recommendation, Teva has come back with a formulation that addresses the concerns of the UK drug advisory body.
CHM described the reformulation work undertaken by Teva as “extensive.” More importantly, data it started reviewing in February suggest the safety and efficacy of the tablets are acceptable. Teva presented data from clinical trials in volunteers showing its reformulated levothyroxine tablets cause thyroid levels in the blood to increase to levels equivalent to those associated with the reference product. CHM also thinks changes to the formulation and manufacturing process will ensure future batches of Teva’s tablets remain equivalent to the reference product throughout their shelf lives.
In reformulating the product, Teva has removed lactose from the tablets. The change means its new formulation can be taken by patients who are intolerant of galactose — a product of the breakdown of lactose — or have some other conditions. Teva has also added new tablet strengths to its portfolio. In addition to 50 and 100 microgram tablets, Teva is making 12.5 and 25 microgram versions. CHM said the broader range will help patients take the right dose without having to split tablets.