There have been a number of developments in biosimilars of late, including regulatory approvals in Canada issued on January 15, 2014 for two biosimilar products, REMSIRA and INFLECTRA, which are versions of the monoclonal antibody product infliximab, using REMICADE as the reference product.  Developments in other jurisdictions continue.  With patent protection on biologic originator drugs claimed to be close to an end on some top-selling products in some jurisdictions, we may soon see an increase in applications and market approvals for these products.

Canada and EU:  recent approvals

On January 15, 2014, Health Canada approved two infliximab subsequent entry biologic ( SEB) products (termed “biosimilars” elsewhere) in the name of Celltrion Healthcare Co Ltd., a Korean-based company.  The products are authorized under two names, REMSIMA and INFLECTRA, although they are essentially the same product.  The products are subsequent entry products to the innovative product, REMICADE.  A review of the Canadian product monographs informs that the products were not approved for all indications of the reference product, REMICADE.

In the EU, two products under the same names were authorized in 2013.  Although a Celltrion company obtained the authorization for REMSIMA in the EU, it was Hospira who obtained EU authorization for INFLECTRA. The manufacturing process and clinical data submitted for the two products were identical in the EU. For the REMSIMA and INFLECTRA products in the EU, several of the same indications as existed for REMICADE were approved even though the reported study concerned only rheumatoid arthritis. An additional study concerned ankylosing spondylitis.

Since approval of infliximab, 2 further biosimilar products have been authorized by the European Medicines Agency, namely,  Ovaleap (follitropin alpha) and Grastofil (filgrastim), although other versions of this latter product had previously been approved in the EU.

France:  New rules on reimbursement that implicate biosimilars

In France, as of 1st January 2014 new provisions have been in force concerning biosimilars.

Article 47 of the Law of 23 December 2013, concerning the budget of the Social Security, has adapted provisions which allow the substitution of originators by generics to extend to biosimilar products.  Specifically, the rule concerning generics is that, with the exception of certain specific cases, they must be substituted for an originator product if and when both are listed by the health authorities (ANSM) within the same ‘generic group’.

As of January 1, 2014, groups of similar biologic products may now also be established by the ANSM, and will be treated in the same manner from the payor’s perspective.  This means that when prescribing a biologic product, physicians are required to specify on the prescription whether this is the first time the biologic product is prescribed. If it is, the pharmacist must fill the prescription with the least costly product within the group of biologic products, typically, the biosimilar.  

However, if treatment has been started with a given product, be it an originator or a biosimilar, the physician will specify that the product shall not be substituted as the treatment must continue with the same biologic.

Of interest, the ANSM has reported the following as dates at which patent protection in France will end:

Orencia Abatacept : 2019 Humira Adalimumab : 2016 Avastin Bevacizumab : 2018 Erbitux Cetuximab : 2016 Enbrel Etanercept : 2011 Tysabri Natalizumab : 2018 Xolair Omalizumab : 2017 Synagis Palivizumab : 2012 Mabthera Rituximab :  2015 Herceptin trastuzumab : 2014

It remains to be seen whether biosimilar applications will be approved for these products, although recent press reports indicate that trials are ongoing in respect of biosimilar versions of HUMIRA as well as HERCEPTIN.  

United States: Status update

In the United States,  the Biologics Price Competition and Innovation Act of 2009 (“BPCI Act”) passed under the Patient Protection and Affordable Care Act (“ACA”) of 2010 provides an abbreviated licensure pathway for the U.S. Food and Drug Administration (“FDA”) to approve biologics.  As of September 17, 2013, there are no biosimilar biological products have been licenced under the new law.  However,17 Investigational New Drug (IND) Applications for biosimilar development programs have been submitted to the FDA and additional development programs are proceeding. The FDA is holding development-phase meetings and providing written advice to manufacturers for ongoing biosimilar products development programs.

To date, the FDA has issued notices in the Federal Register of three draft guidance documents on biosimilar product development: 1) Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; 2) Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product; and 3) Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009. Also available is a draft Guidance for Industry entitled Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants, which has not been published in the Federal Register. The FDA has not yet issued any final rules on this topic.

Meanwhile, the FDA has been authorized to assess and collect fees for biosimilar biological products from October 2012 through September 2017 under the Biosimilar User Fee Act (“BsUFA”).  According to the November 15, 2013 statement by Dr. Woodcock before Congress, the BsUFA program “includes fees for products in the development phase to generate fee revenue in the near-term and to enable sponsors to have meetings with FDA early in the development of biosimilar biological product candidates.”