Industry Trend Analysis - Record Biosimilar Approval Rates Are Anticipated For 2018 - FEB 2018

BMI View: 2017 witnessed a noticeable spike in biosimilar approvals in both the US and EU. However, in the US, the issue of interchangeability is still to be resolved, which is becoming increasingly important. A lack of interchangeability guidance will dampen the market potential for biosimilars, and although resolution is unlikely in 2018, FDA guidance can be expected. In both the US and the EU, approval for biosimilar pegfilgrastim looks likely in 2018, but there will be a race amongst several companies to be first, including Sandoz.

2017 has proved to be an exceptional year for biosimilars. In the US, the FDA approved four biosimilars using the regulatory pathway developed through the Biosimilars Price Competition and Innovation Act (BPCIA); a small figure, but doubling the total number of biosimilars approved via this pathway prior to 2017. In the EU, there were 15 biosimilar approvals in 2017, although there are some caveats over the types of products approved that make comparisons with the US difficult. Nonetheless, on both sides of the Atlantic there were record numbers of biosimilar approvals, highlighting the growing market.

2017 Saw Record Number Of Biosimilar Approvals
Total Biosimilar Approvals In US And EU
Source: US FDA, EMA, BMI

Amongst the products approved by the FDA in 2017 were Amgen's Mvasi (bevacizumab-awwb), a biosimilar version of Genentech ( Roche)'s Avastin and the first biosimilar to be approved for use in treating cancer. In December, Mylan and Biocon's Ogivri (trastuzumab-dkst) was approved. The product, a biosimilar version of Genentech's Herceptin, was the first biosimilar to be approved for use in treating certain cancers, including certain types of breast and stomach cancer. These two approvals have opened up the US market to biosimilar versions of cancer treatments for the first time; given the size of the cancer market and the high cost of modern biologic treatments, more such biosimilar approvals can be expected in 2018.

FDA Biosimilars Approved
Company Biosimilar Name Reference Product (Company) Approval Date
Source: US FDA, BMI
Sandoz Zarxio (filgrastim-sndz) Neupogen (Amgen) Mar-15
Celltrion/Hospira Inflectra (infliximab-dyyb) Remicade (Janssen Biotech) Apr-15
Sandoz Erelzi (etanercept-szzs) Enbrel (Amgen) Aug-16
Amgen Amjevita (adalimumab-atta) Humira (AbbVie) Sep-16
Samsung Bioepis Renflexis (infliximab-abda) Remicade (Janssen Biotech) May-17
Boehringer Ingelheim Cyltezo (adalimumab-adbm) Humira (AbbVie) Aug-17
Amgen Mvasi (bevacizumab-awwb) Avastin (Roche) Sep-17
Mylan Ogivri (trastuzumab-dkst) Herceptin (Roche) Dec-17

The four US biosimilar approvals in 2017 also marked the debuts of three companies to the US biosimilar market: Samsung Bioepis, Boehringer Ingelheim and Mylan (along with its partner, Biocon). None of these three are entirely new to biosimilars, but the fact that they have now overcome regulatory hurdles in the US is significant, and underscores the development and production abilities of all three.

The FDA's 2017 biosimilar approvals is notable also because two of the four to be approved are second biosimilar entrants: Samsung Bioepis' Renflexis (infliximab-abda, launched in the US by Merck & Co) will compete with both Celltrion/ Hospira ( Pfizer)'s Inflectra (infliximab-dyyb) and the reference product, Janssen Biotech ( Johnson & Johnson)'s Remicade; whilst Boehringer Ingelheim's Cyltezo (adalimumab-adbm) will compete with both Amgen's Amjevita (adalimumab-atta) and the reference product, AbbVie's Humira.

The approvals of Renflexis and Cyltezo represent the opening in the US of a competitive biosimilar market, with one innovative version and two biosimilar versions in both cases, all competing for market share. However, these approvals have also served to highlight what is perhaps the biggest problem with the US biosimilar market that has not yet been resolved: interchangeability. None of the eight biosimilars so far approved in the US are interchangeable with their reference products, or in the cases of Inflectra and Renflexis, and Amjevita and Cyltezo, with each other. This will undoubtedly dampen competition, as patients who are currently prescribed the innovative versions will not be able to be switched to the biosimilars, and similarly new patients prescribed with any of the biosimilars will not be able to switch easily to the innovative version or other competing biosimilar versions. The question of interchangeability is one that the FDA has proved unwilling to address, but as the biosimilar market now begins to develop with multiple versions of products approved, this is an issue that will become increasingly important. Resolution in 2018 is unlikely, but the FDA will certainly feel pressure to address this aspect of the market. Draft guidance can be anticipated.

In The EU

2017 has also proved to be an exceptional year for biosimilars in the EU as well. Similarly to the US, more biosimilars were approved by the EMA in 2017 than in any other year. However, the EU biosimilar market is much more advanced than its US counterpart, and whilst the US saw a record high of four approvals in 2017, in the EU a record high of 15 biosimilar approvals was achieved. There are some caveats, however, that make direct comparisons between the EU and the US difficult. In the EU, insulin products are regarded as biosimilars, and one of the 15 approvals was for Merck Sharp & Dohme's Lusduna (insulin glargine), whilst another was for sanofi-aventis groupe's Insulin lispro Sanofi. In the US, insulin is not regarded as a biosimilar, and insulin products are consequently not approved through the BPCIA's regulatory pathway. As a result, insulin products will not appear in the FDA's lists of biosimilars.

The EMA's biosimilar approvals in 2017 also include several instances where different versions of the same biosimilar from the same company have been approved under separate brand names. For example, two separate versions of Amgen's adalimumab, Solymbic and Amgevita, were both approved on March 22. Similarly, two separate versions of Sandoz ( Novartis)'s rituximab, Riximyo and Rixathon, were both approved on June 6; and three separate versions of Celltrion's rituximab, Rituzena, Ritemvia and Blitzima, were all approved on July 13 2017. Consequently, 11 of the 15 biosimilars approved by the EMA in 2017 were arguably new, a figure that further reduces to nine if the two insulin products are disregarded. Nonetheless, 2017 proved again that the EMA is considerably ahead of the FDA in developing a biosimilar market.

Biosimilars Approved In The EU
Company Biosimilar Name Active Substance Date of Authorisation
Source: EMA, BMI
Sandoz (Novartis) Omnitorope Somatropin April 12 2006
Hexal (Sandoz) Epoetin Alfa Hexal Epoetin alfa August 28 2007
Sandoz (Novartis) Binocrit Epoetin alfa August 28 2007
Medice Arzneimittel Abseamed Epoetin alfa August 28 2007
Stada Arzneimittel Silapo Epoetin alfa December 18 2007
Hospira (Pfizer) Retacrit Epoetin alfa December 18 2007
Teva Pharmaceutical Industries Tevagrastim Filgrastim September 15 2008
ratiopharm (Teva Pharmaceutical Industries) Ratiograstim Filgrastim September 9 2008
AbZ-Pharma Biograstim Filgrastim September 15 2008
Sandoz (Novartis) Zarzio Filgrastim February 6 2009
Hexal (Sandoz) Filgrastim Hexal Filgrastim February 6 2009
Hospira (Pfizer) Nivestim Filgrastim June 8 2010
Celltrion Healthcare Hungary Remsima Infliximab September 10 2013
Hospira (Pfizer) Inflectra Infliximab September 10 2013
Teva Pharmaceutical Industries Ovaleap Follitropin alfa September 27 2013
Apotex Europe Grastofil Filgrastim October 18 2013
Finox Biotech (Gedeon Richter) Bemfola Follitropin alfa March 27 2014
Eli Lilly/Boehringer Ingelheim Abasaglar (previously Abasria) Insulin glargine September 9 2014
Accord Healthcare Accofil Filgrastim September 18 2014
Samsung Bioepis/Biogen Benepali Etanercept January 14 2016
Samsung Bioepis/Biogen Flixabi Infliximab May 26 2016
Pharmathen Thorinane Enoxaparin sodium September 15 2016
Techdown Europe Inhixa Enoxaparin sodium September 15 2016
Gedeon Richter Terrosa Teriparatide January 4 2017
Merck Sharp & Dohme Lusduna Insulin glargine January 4 2017
Stada Arzneimittel Movymia Teriparatide January 11 2017
Celltrion Healthcare Hungary Truxima Rituximab February 17 2017
Amgen Solymbic Adalimumab March 22 2017
Amgen Amgevita Adalimumab March 22 2017
Sandoz (Novartis) Riximyo Rituximab June 6 2017
Sandoz (Novartis) Rixathon Rituximab June 6 2017
Sandoz (Novartis) Erelzi Etanercept June 23 2017
Celltrion Healthcare Hungary Rituzena (previously Tuxella) Rituximab July 13 2017
Celltrion Healthcare Hungary Ritemvia Rituximab July 13 2017
Celltrion Healthcare Hungary Blitzima Rituximab July 13 2017
sanofi-aventis groupe Insulin lispro Sanofi Insulin lispro July 19 2017
Samsung Bioepis UK Ltd Imraldi Adalimumab August 24 2017
Boehringer Ingelheim International Cyltezo Adalimumab November 10 2017

In the EU, there were approvals for three entirely new biosimilars, with various versions of adalimumab, rituximab and teriparatide being approved during the year. By comparison, only one of these, adalimumab, gained a first biosimilar approval in the US in 2017. However, this does arguably give an indication of what biosimilars can be expected to be approved in 2018 and beyond in the US, as a number of companies that have gained approvals in the EU since 2006 also operate in the US.

Looking at all the approvals for biosimilars so far granted in both the EU and the US, it is clear that Sandoz is taking an early lead in terms of companies with the most approvals. Altogether, the firm and its subsidiaries have received ten approvals for five different biosimilars. The company has led from the beginning: its biosimilar version of somatropin, marketed as Omnitrope, gained EMA approval in April 2006, making it the first biosimilar approved in the EU. It was also the first company to gain approval for a biosimilar in the US, when the FDA approved its filgrastim product, Zarxio, in March 2015. It is likely that Sandoz will achieve regulatory approvals in the EU and US for its biosimilar pegfilgrastim in 2018, for which it is poised to be the first to gain approval for such a biosimilar. However, this programme did suffer some setbacks in 2017, with a complete response letter being issued by the FDA and the MAA in the EU being withdrawn. Other companies are also looking to gain approvals for biosimilar pegfilgrastim, notably Mylan and Apotex, but Mylan has also received a CRL from the FDA. It is likely that 2018 will therefore see a number of pegfilgrastim approvals in both the EU and US.