Samsung RA Biosimilar EU Uptake Tied to Perceived Cost Despite Physician Concerns

• Reference companies may lower drug prices too

• Payers may mandate biosimilar use in tender markets

• Immunogenicity reactions give pause for switching

Samsung Bioepis’ three rheumatoid arthritis (RA) biosimilar candidates - SB4, SB2 and SB5 - will lead to pricing wars in the cost-conscious EU once approved, experts said. Anticipated drug costs in turn will impact market uptake but rheumatologists expressed concern they may be shut out of the decision-making process.

Several said they preferred to have patients, especially well-controlled ones, stick with standard of care for fear of immune reactions.

Samsung Bioepis is a joint venture between Samsung Biologics and Biogen (NASDAQ:BIIB).

Benepali, formerly known as SB4, is a biosimilar to Amgen (NASDAQ:AMGN) and Pfizer’s (NYSE:PFE) Enbrel (etanercept). It received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP), according to a 23 November 2015 press release. The company awaits a CHMP opinion on SB2, its biosimilar to Johnson & Johnson’s (NYSE:JNJ) Remicade (infliximab). The company will submit an MAA for SB5, its biosimilar to AbbVie’s (NYSE:ABBV) Humira (adalimumab), in 2016, according to company information.

This news service reported on 11 December that all three biosimilars are likely to be approved in the EU based on equivalence data.

Samsung did not respond to a request for comment.

Total global sales of Enbrel for all indications peaked in 2015 at USD 8.5bn, according to BioPharm Insight data. Total global sales of Remicade for all approved indications also peaked in 2015 at USD 8.5bn. Total global sales of Humira for all indications are expected to peak in 2018 at USD 17.1bn, according to BioPharm Insight data.

Pricing wars to ensure

The EU is aggressive about trying to save costs so biosimilars - with their anticipated lower sticker prices to originator drugs - are keenly eyed, said Dr Lee Simon, rheumatologist, former division director of analgesic, anti-inflammatory and ophthalmologic drug products, FDA, Cambridge, Massachusetts. If these drugs are priced correctly - and there will be aggressive negotiations - they will get market uptake, he said.

Considering the European introduction already of other biosimilar monoclonal antibodies to Remicade like Pfizer/Hospira’s Inflectra and Celltrion’s (KOSDAQ:068270) Remsima, a pricing war is inevitable, agreed Steven Bradshaw, managing director & head of European Office, Market Access Solutions, London, UK.

A price decline of 69% for a Remicade biosimilar by Finnish company Orion Oyj in Norway may set the stage for volatile biosimilar pricing negotiations in some countries, said Bradshaw and Tim Riley, CEO, The Wellstate Group, London, UK. These could affect decisions on whether innovators or biosimilars will get the lion share of the market. However, it’s unlikely that in the UK, France or Germany there will be such price declines, Bradshaw said, noting that may be unsustainable for biosimilar makers in the long-term. Inflectra/Remsima are about 15- 30% lower than Remicade in the aforementioned countries, he added.

As biosimilars come to market, reference product companies lower the price of their drugs, diluting the financial advantage of biosimilars, explained Bradshaw and Dr Rene Westhovens, professor, University of Leuven, Leuven, Belgium. When the competition is gone, the reference companies can raise their prices again, he said.

Innovator companies can also play into brand loyalty for market wars, Bradshaw said. They may make the case there can be assurance of product supply continuity as opposed to manufacturing uncertainty with these newer biosimilar developers, he said. Innovators may also try to steer the market by offering valueadded services like at-home devices making administration easier or employ scare-mongering about biosimilar safety or quality, he said.

As biosimilars come to market, reference product companies lower the price of their drugs

Treatment decisions

In a new patient there is no reason not to prescribe a biosimilar, Westhovens said. For many physicians and patients, they prefer to use a drug that’s been on the market longer, even if two drugs are considered to be equivalent, Dr Gilberto Castaneda Hernandez, investigator, department of pharmacology, Research Center, Mexico City, Mexico differed.

Physicians want the opportunity to decide how to treat their treatment-naive patients, Westhovens explained. However, eventually some government authorities or hospitals may force rheumatologists to switch patients to biosimilars, he said. Lee added physicians will have little say on biosimilar uptake.

In tender-based markets, payers mandate physicians switch to the lowest-cost products but in others the ultimate choice remains with the physician, Bradshaw said. In the UK, physicians opting for more expensive innovative biologics have to provide compelling justification versus a less expensive alternative, Riley said.

The uptake of biosimilar from country to country will also vary based on patent expiration which differs across countries in the EU, said Dr Jiri Vencofsky, professor of medicine, Charles University, Prague, Czech Republic. In Denmark, Norway, Ireland, the UK and France, biosimilars are recommended to be used first, he added.

In a patient that is well-controlled on Remicade, physicians would prefer not to be obligated to switch to a biosimilar because of the chance of immunological reactions, Westhovens said.

Switching from Enbrel to a biosimilar has less of a chance of negative reaction than Remicade to biosimilar, because Remicade is a chimeric which creates higher immunogenicity, said an investigator at the recent American College of Rheumatology (ACR) conference.

Payers are not so concerned about tolerability issues unless they are particularly egregious, Bradshaw said.

In some cases, uptake may favor the biosimilar, as with Benepali, Hernandez noted. At 52 weeks, there were 52 injection site reactions with Enbrel versus 11 with Benepali, which is typically due to the vehicle and injection device, he explained. It appears Benepali is manufactured with an improved pharmaceutical technology compared to innovator product, therefore patients might prefer Benepali, he said. To actually show preference, a specific study addressing this would be required, however, he added.

Additionally, rheumatologists are excited about the prospect of another option for patients if immunogenicity does become an issue in the originator anti-TNF, said Dr Jean Satish, lecturer, molecular and clinical pharmacology, University of Liverpool, UK.

Rheumatologists also worry that in addition to being forced to switch patients, biosimilars might be approved across indications, or extended to the other indications for which the originator is approved, explained Dr Nathan Wei, rheumatologist, Arthritis Treatment Center, Frederick, Maryland. Just because biosimilars are shown to be equivalent in one indication does not necessarily mean that equivalence can be extrapolated across indications which makes rheumatologists nervous if they perceive payers determine treatment, he explained.

April 4, 2016

Jennifer C. Smith-Parker

Journalist, London

Jennifer is an award-winning biopharmaceutical industry journalist. Prior to joining BioPharm Insight Jennifer was Associate News Editor at FDA Week, covering FDA regulatory policy for all FDA-regulated product areas. She also worked at The Monitor, where she covered health, environment and science issues and conducted a year-long project on indigent healthcare services. She was awarded the Texas Medical Association’s Anson Jones journalism award for an article on breast cancer. Jennifer graduated from New York University with a Bachelor’s with Honors in History and Journalism. Follow her on Twitter @JsmithParker

Alissa Fleck

Journalist, New York

Alissa is a former freelance editor and journalist who has been a regular contributor for Bankrate, the Huffington Post, Truthout, Global Post and three Straus News publications in Manhattan. She has written medical and health copy for websites including SF Gate (the San Francisco Chronicle online) and Livestrong as well as for private clients.