After months of speculation, Celltrion has received backing from the CHMP, suggesting that the EMA will approve its first biosimilar monoclonal antibody, Remsima, within the next 3 months. But why is this such an important event? Well, there are several reasons:

  • Adoption of indication extrapolation - The CHMP has recommended approval of Remsima for all six indications that the reference brand, Merck & Co's Remicade, is licensed. Although indication extrapolation has been allowed before, this is the first time it has been accepted across different therapy areas (e.g. from rheumatology to gastroenterology) and with a highly complex molecule.
  • Validation of South Korean expertise - Celltrion could be the first small biotech company from outside Europe or the US to launch a biosimilar in Europe; BioPartners did gain EMA approval of Valtropin, but the product was never launched, while MJ Group has tried twice without success to gain EMA approval of its biosimilar insulins.
  • Savings to healthcare budgets - Remsima marks the beginning of the next wave of biosimilars; the uptake of biosimilars to date has been slow in many of the larger European markets, although considerable heterogeneity is evident, but those on the market today are simpler recombinant proteins, which offer relatively small cost savings. The now-imminent launch of the first biosimilar monoclonal antibody holds the potential to save over-stretched healthcare budgets millions of Euros.
  • New specialties will gain experience with biosimilars - Remsima has been recommended for approval for indications treated by dermatologists, rheumatologists and gastroenterologists; therefore, Remsima represents the first opportunity for these specialists to gain first-hand experience of a biosimilar.

Perhaps the biggest uncertainty surrounding Remsima, prior to the CHMP's positive opinion, was whether approval would be granted for all six indications, because Celltrion had only clinically tested Remsima in rheumatoid arthritis and ankylosing spondylitis patients. Remicade captures around 40% of its sales in dermatological and gastrointestinal diseases. Without regulatory approval for indications in these therapy areas, Celltrion's market would have been significantly constrained and confidence in the product's similarity to the brand may have been marred.

Although the EMA has permitted indication extrapolation for biosimilars in the past, this has so far only been applied to relatively simple recombinant proteins and the extrapolated indications have been closely related to the studied indication; for example, Nivestim (biosimilar filgrastim) was clinically studied in chemotherapy-induced neutropenia, but was also approved for neutropenia related to myeloablative procedures, chronic infections and HIV. Those in the biosimilar industry have been watching closely to see how European regulators would react to a biosimilar application seeking indication extrapolation for a more complex biologic targeting diseases in multiple therapeutic areas. The CHMP's backing of approval for all indications is not only a major positive for Celltrion, but also a promising indicator to other biosimilar developers that are hoping to gain approval across unstudied indications as well.

Despite this groundbreaking, positive news for the biosimilar sector, the challenges are not over for Celltrion. The EMA does typically follow the advice of the CHMP so approval is expected in the coming months. However, it could be years before Celltrion begins to reap meaningful rewards from its first biosimilar:

  1. Remicade's key patent has been extended until February 2015, delaying launch in the major five EU markets (France, Germany, Italy, Spain and the UK); Remsima has already been approved in some Eastern European markets such as Moldova (as Flammegis), as well as South Korea, but given the small size of these markets, sales are expected to be modest.
  2. Most rheumatologists are only moderately familiar with the concept of biosimilars, according to Decision Resources? primary market research, and they express concerns about possibly significant differences between the biosimilar and brand; this wariness among rheumatologists will likely translate into slow uptake.
  3. Gastroenterologists have told Decision Resources that they have concerns about indication extrapolation. Without supportive clinical data for Remsima in ulcerative colitis or Crohn's disease, uptake among gastroenterologists will like be more hesitant than among rheumatologists.
  4. Payers in most European countries have done little to stimulate uptake of biosimilars to date; this suggests that Celltrion, and its partner Hospira, will need to invest in physician/pharmacist/payer educational programs to gain traction among these key stakeholders.
  5. European physicians and payers surveyed by Decision Resources place significantly less trust in companies from countries outside of the US and Europe. Celltrion will need to consider strategies to improve levels of trust among key stakeholders.

Many more challenges await Celltrion as it nears this landmark event, but the company's achievements to date are impressive and will no doubt boost the number of suitors contemplating an acquisition of the South Korean firm.

Kate Keeping is a director of biosimilars research at BioTrends Research Group.

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