close up of an antibody

Most people associate passage of the US Patient Protection and Affordable Care Act or ACA, (otherwise known as Obamacare) with extending health benefits to the under- and uninsured.

But the legislation, signed into law in 2010, also includes the Biologics Price Competition and Innovation (BPCI) Act, which created an abbreviated licensure pathway for biological products demonstrated to be “biosimilar” to or “interchangeable” with a biological product licensed by the Food and Drug Administration (FDA).  In March 2015, the FDA finally approved the first biosimilar drug for use in the US—Sandoz’ immune-boosting drug Zarxio® for cancer patients undergoing chemotherapy. How this approval, and presumably others to follow, reshapes the world’s largest biologics market remains an open question. The trade magazine Chemistry World recently reported that, as of October 2014, the FDA had received nearly 80 requests from companies for initial meetings to discuss biosimilar development programs for 14 different originator products, and had received 28 Investigational New Drug Applications (INDs) for biosimilar development programs. The European Medicines Agency (EMA), which issued final versions of the guidelines in 2005, and authorized the sale of biosimilars the following year, has since approved 20 biosimilar products, with more on the way. In early May 2015, the EMA said it would review a biosimilar candidate for the rheumatoid arthritis drug Enbrel® (etanercept).

Analysts estimate the advent of biosimilars could produce anywhere from US$44 billion to US$250 billion in US health-care savings over the next decade. This wide range in estimates goes to the heart of just how many unknowns are circling this nascent industry. There are many different factors impacting whether the biosimilar industry will be successful and what constitutes success.

Right now, many companies are developing biosimilars to the same originator product. In Europe, for instance, there are four different biosimilars for the cancer drug Avastin that are all competing against each other. It has been predicted that they will come in 20% to 30% cheaper than the originator, but if the biosimilar market is then fragmented, lower sales may not support this pricing. Unlike a generic small-molecule drug, there are less cost-savings because you still have production costs—which are high—and on top of that the whole application process for a biosimilar can be hundreds of millions of dollars. The BPCI Act contains two different layers of approval: biosimilarity and interchangeability. It grants 12 years of data exclusivity to the branded biologic before approval of the biosimilar, which the biotech industry pushed for strenuously, and exclusive rights of 12-14 months to the first biosimilar of a branded biologic found to be interchangeable.

But there are still significant questions to be sorted out regarding the development, licensing and regulation of biosimilars. For instance, the FDA is the only regulatory agency that makes a distinction between biosimilarity and interchangeability—whether the biosimilar is the same as the originator—but lack of specific guidance from the FDA has, in the opinion of many, slowed the development and approval process. For interchangeability to happen, the FDA will expect the biosimilar to produce the same clinical result as the originator product in any given patient.  Additionally, the risk of alternating between the biosimilar and the originator product is no greater than sustained use of the originator product.  Over the long run, having interchangeability means the biosimilar can be substituted by the pharmacist for the originator product without the involvement of the health care provider who wrote the initial prescription, which is the case now for generic drugs. If the producer of the biosimilar product can establish interchangeability, sales of biosimilars will be greater and more beneficial to the Sponsor. In Europe, where biosimilars are on the market, each nation or state is allowed to make a decision on interchangeability.

The Zarxio approval by the FDA could help drug developers by enabling them to finally go back and look at source documents for the biosimilar to see what was done for that program. This is important because taking a biosimilar and comparing it to the originator is complex.  It is a challenge for companies to obtain enough lots of the originator product, in different regions in the US and Europe, to do the necessary studies. And while there are a lot of regulatory documents out there, they do not specifically outline how to design these studies. What we do have now, though, with the Zarxio approval, is a package of documents that the public can review that show what a particular company did to prove biosimilarity. And unlike Europe, the US Freedom of Information Act (FIA) provides access to these documents. With that said, it is unlikely that the US will grant interchangeability any time soon. The FDA has been very cautious because even minor changes in the production process can have a significant impact on the efficacy and safety of the end product.  This happened when the formulation of the anemia drug epoetin-á. was changed by the originator after it was marketed outside the United States and caused pure red cell aplasia. And this change was made by the originator. So it is possible the FDA has likely concluded that if one manufacturer can’t control their own product, what are the chances a biosimilar can do the same thing?

By Christina Satterwhite & Niall DinwoodieCharles River Laboratories

But the legislation, signed into law in 2010, also includes the Biologics Price Competition and Innovation (BPCI) Act, which created an abbreviated licensure pathway for biological products demonstrated to be “biosimilar” to or “interchangeable” with a biological product licensed by the Food and Drug Administration (FDA).