Generic Biologic Drugs Appear Equivalent to Brand Name Counterpart

A recent analysis from Johns Hopkins University Bloomberg School of Public Health researchers found that generic forms of the biologic drug infliximab (remicade) appear to be just as safe and effective as the brand name version. The researchers analyzed 19 studies conducted through April 2016 and determined that, although the sample size was small, biosimilar drugs had safety and effectiveness profiles that were very similar to their branded counterparts. “Preliminary evidence supports the biosimilarity and interchangeability of biosimilar and reference TNF-α inhibitors,” they concluded in their study.

Infliximab is a biologic drug indicated to treat rheumatoid arthritis, inflammatory bowel disease, and psoriasis. It is in a class of drugs known as tumor necrosis factor-alpha (TNF-α) inhibitors, which suppress the body’s inflammatory response. Infliximab is one of several TNF-α inhibitor biologics that have received approval in recent years for autoimmune diseases—a lineup that includes adalimumab (Humira) and etanercept (Enbrel).

The Biologics Price Competition and Innovation Act (BPCIA) was passed in 2009, enabling biosimilars to compete with branded biologics. This law was considered to have potential to enhance patient access to advanced therapies through lower drug costs resulting from greater competition among drug manufacturers. In many ways, it was, and still is, viewed as the Hatch-Waxman Act for biologics.

Despite the BPCIA, the FDA has approved just 2 biosimilars: Zarxio, a biosimilar of filgrastim (Neupogen), and Inflectra, a biosimilar of infliximab (Remicade). Because biologic drugs are large, complex molecules manufactured from living organisms, such as bacteria and yeast, opponents of generic biologics argue that it is impossible to replicate copies that are completely identical. This, they say, could mean that certain patients could have variances in clinical response or even adverse reactions to the subtle differences of biosimilars.

“The billion-dollar question has been whether these ‘generic biologics’ are the same as the brand name versions,” says study leader G. Caleb Alexander, MD, an associate professor in the Department of Epidemiology at the Bloomberg School and co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, in a press release. “The same debate occurred with the advent of less complicated generic drugs, and now it’s being hashed out all over again with much more at stake—more room for error and more potential for cost savings to the health system. But based on the available evidence, we conclude that the products we studied appear comparable, and they will definitely be cheaper.”

Biologics are used to treat cancer, HIV/AIDS, Alzheimer’s disease, and other life-threatening diseases. Developing lower-cost versions of these crucial drugs has the potential to assist a wide swath of the US population who might otherwise be unable to afford their medications. In fact, a recent analysis from the IMS Institute for Healthcare Informatics found that biosimilars have the potential to save the global health system $110 billion by 2020.

To receive FDA approval, manufacturers must show that the biosimilar is “highly similar” to the reference product, omitting minor differences in clinically inactive components. They must also demonstrate that, compared with the reference biologic, there are no clinically meaningful differences in terms of safety, purity, and potency.

In addition to approval, a biosimilar may receive an added interchangeability designation from the FDA, allowing it to be substituted for the reference biologic at the point of dispensing without the prescriber’s involvement. Because of this, biosimilars with this designation are ideal candidates for pharmacist substitution akin to generics, the authors explained.

When approaching such interchangeable biosimilar substitution, pharmacists should consider the following questions, which the researchers based on the current process for generic substitution:

• Does state law give pharmacists the authority to autonomously substitute interchangeable biosimilars or will the prescriber need to be contacted?
• What criteria define which products may be substituted?
• Is the biosimilar considered interchangeable with the prescribed product for all indications? If not, what indications can be substituted?
• Does the state require prescriber and/or patient notification or counseling?
• Does the state require recordkeeping of drugs dispensed and any related notifications of dispensing or substitutions?
• Is the patient being switched from one product to another? If so, are there any differences in packaging, excipients, devices, or other issues that require counseling?
• What is the scope of state legislation on substitution of interchangeable biosimilars by pharmacy practice setting?

“Our study should reassure clinicians and patients and, importantly, the folks who pay the bills—insurance companies and government programs, like Medicare—that biosimilar TNF-α inhibitors appear comparable to their branded counterparts based on the evidence we have thus far,” noted Dr. Alexander in the press release. “Hopefully, this will encourage the brisk adoption of these products. There is no question that greater competition in this market will benefit patients, prescribers, and society in the long run.”