On 29 April, Samsung Bioepis announced the approval by the US Food and Drug Administration (FDA) of Eticovo (etanercept-ykro), a biosimilar version of Amgen ’s Enbrel, across all eligible indications including rheumatoid arthritis (RA), ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, and polyarticular juvenile idiopathic arthritis.

Samsung Bioepis’ Eticovo

However, it remains unclear as to when the drug will actually be made available for doctors to prescribe, as patent protection for Enbrel in the US extends into the next decade. The future prospects for Eticovo may be clarified in the next few months by ongoing litigation related to another etanercept biosimilar, Sandoz ’s Erelzi (etanercept-szzs).

Erelzi was approved by the FDA in August 2016 but has yet to see a single sale in the US. In February 2016, Amgen sued Sandoz under the Biologics Price Competition and Innovation Act (BPCIA), claiming that Sandoz’s abbreviated biologics license (aBLA) infringed on five patents covering Enbrel including methods of manufacturing and specific therapeutic uses. Three out of the five patents covered the usage of Enbrel for the treatment of psoriasis and psoriatic arthritis, two of the indications for which Erelzi was eventually approved.

In July 2017, Sandoz responded by seeking FDA approval for an amended label for Erelzi that deleted these two indications. The FDA approved this request in January 2018. This method of “skinny labelling” has long been used by companies that produce generic small molecules to side-step patent protections but has been an uncommon strategy among biosimilar developers.

In December 2017, Amgen moved for summary judgement on Sandoz’s possible infringement of one of the psoriasis patents. Sandoz responded that since it had carved the psoriatic conditions from Erelzi’s label, Amgen’s infringement claims were now irrelevant. Initially, Amgen argued that Sandoz had already committed an act of infringement by filing the aBLA with the original label, but eventually the company conceded, dropping all three psoriatic disease treatment patents from its suit. The trial began in September 2018 and a ruling is expected in H1 2019. If the ruling finds in Sandoz’s favour, it is highly likely that Amgen will appeal, dragging out the timing of any potential launch by at least one year.

Whether or not the skinny-labelling strategy will work for Erelzi and potentially other Enbrel biosimilars like Eticovo remains to be seen. For the two remaining patents protecting Enbrel in the suit, which relate to the construction of the tumour necrosis factor (TNF) receptor fusion protein and a method used to make the protein, Sandoz argues that the methods used in the patents are so obvious that the patent itself should be invalidated. However, proving these arguments in a court of law might be difficult.
Even with a skinny label, if Erelzi and potentially Eticovo are able to launch in the US sooner than 2029, the impact on Amgen’s bottom line could be substantial. The skinny label would still include RA, an indication that netted Enbrel sales of about $3.6B in the US in 2018 and is projected to earn annual sales of between $3.3B and $3.5B through to 2027, according to an analysis by GlobalData. The combined sales of Enbrel in psoriasis and psoriatic arthritis, the carved-out indications, represent only a fraction of its RA sales.

However, the exact effect of an early etanercept biosimilar launch is difficult to predict and will likely depend on whether any major changes are made to the healthcare regulatory framework in the US. For example, following the recent US rollout of infliximab biosimilars, the uptake has been surprisingly slow. Based on GlobalData’s analysis, Pfizer’s Inflectra (infliximab-dyyb) and Samsung Bioepis’ Renflexis (infliximab-abda) only commanded about 6% of the US infliximab market for RA in 2018. In contrast, nearly 24% of the Europe infliximab market was already claimed by these copy-cat drugs in 2017, a similar timespan after the European launch of the biosimilars.

One of the main issues thought to be hindering the uptake of biosimilars in the US is biosimilar companies’ inability to provide competitive enough discounts to payers. Payers often have already negotiated volume-based discounts and other rebates with the company producing the reference product. These negotiations are confidential and the discounts are quite substantial, making it difficult for biosimilars to compete. However, it should be noted that there is still a possibility that the infliximab precedent may not end up applying to etanercept, particularly if drastic cost-cutting measures proposed by the Trump administration are put into effect in the US, which could better support the uptake of biosimilars in the future.