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Clinical Opportunities for Biosimilar Insulins

What will be the impact of the new biosimilar insulins now in development?

What does biosimilar mean? A biosimilar product is a copy of a biological molecule that is already approved in the pharmaceutical market. At best they are very similar to the original product. The key question that still has to be answered is whether the minor differences between an “insulin copy” and the original insulin are clinically relevant. Until now, most of the insulin used has been manufactured by a small number of companies, each manufacturing their own insulin formulation that was patented years back. Now many of the patents have expired for current formulations, leading to an open market for biosimilar insulins to be developed. New biosimilar insulins are being manufactured in India and China, where these products have been available on the market for years.

The process of making human insulin has not changed since it was invented about 40 years ago. The process uses genetically modified bacteria or yeast as the production machines. However, recent advances have been made in the production of recombinant proteins, making it possible to manufacture insulin at reduced costs. The methods used to manufacture the insulin are the personal knowledge of the innovator, and no two manufacturers use identical processes, strains of bacteria/yeast or incubation technologies.  With that being said, it is important to realize that the manufacturing process is what makes insulin the unique product it is. When trying to make biosimilar insulins, it is impossible to make identical proteins without knowledge of the original manufacturing process. To elaborate on this further, even if the primary amino acid sequence is identical, it doesn’t mean that the secondary and tertiary structure of the insulin molecule is as well.

In Europe, the Committee for Medicinal Products for Human Use evaluates the use of recombinant proteins such as insulin by following a “centralized procedure of marketing authorization.” The European Medicine Agency (EMA) is the regulatory agency in Europe. The EMA has developed a regulatory pathway to ensure that any insulin, approved as a biosimilar, meets all high-quality requirements as defined by the EMA. These requirements include evidence of therapeutic equivalence when compared to the original product and data that describes the chemical manufacturing characteristics of the product. In addition, clinical trials with a sufficient duration, 6-12 months, must be performed with a primary outcome measure to show incidence of antibodies to the original biosimilar insulin. An addendum was recently added placing emphasis on pharmacokinetic (PK) and pharmacodynamic (PD) profile of the biosimilar compared with the original insulin. Recently EMA approved an insulin glargine biosimilar. The US Food and Drug Administration (FDA), however, denied approval through the biosimilar pathway, but approved it as a new insulin, which required proven performance in several clinical trials. This may prove to be an advantage, because now more clinical data exists for the biosimilar insulin glargine than would have been required. Appropriately, this biosimilar has many advantages such as a well-established marketing channel, manufacturing expertise, and name recognition that has already been established. In addition, the delivery system is a pen, which has become the preferred way to give insulin.

What is coming for the future? Currently there are at least 6 companies that are developing biosimilar insulin products. Insulin formulations that are being developed include both natural protamine Hagedorn (NPH) and insulin mixtures. It is not expected for price reductions to be as drastic as other medications when a generic comes out, but it is expected to be a 15-30% reduction. Price reductions will be limited due to the high investment cost that went into developing and getting approval of the biosimilar insulin. In addition, prices will be affected by the establishment of post-marketing programs as well as the fact that it costs more to manufacture and distribute insulin when compared to aspirin. When looking at the big picture, any cost reduction is substantial because the insulin industry is a multibillion-dollar-a-year industry, so even a small decrease has a substantial effect.

In summary, it is unknown how the introduction of biosimilar medications will change the insulin market. What is known is that more biosimilar medications will be coming to the market in the near future.

Practice Pearls:

  • A biosimilar product is a copy of a biological molecule that is already approved in the pharmaceutical market; at best they are very similar to the original product.
  • Recent advances have been made in the production of recombinant proteins, making it possible to manufacture insulin at reduced costs.
  • It is impossible to make identical proteins without knowledge of the original manufacturing process. It is important to remember that even if the primary amino acid sequence is identical, it doesn’t mean that the secondary and tertiary structure of the insulin molecule is as well.
  • FDA Offers Free, Continuing Education Course to Help Healthcare Providers Understand ‘Biosimilars’

Researched and prepared by Jennifer Zahn, Doctor of Pharmacy Candidate University Of South Florida College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

 

The Emerging Biosimilar Therapeutic Landscape: Scientific Foundations and Clinical Implications. OpenCME. http://eval.opencme.org/wix/p535236781.aspx