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FDA Updates its Thinking on Immunogenicity Studies for Insulin Biosimilars, Interchangeables

Posted 25 November 2019 | By Zachary Brennan 

FDA Updates its Thinking on Immunogenicity Studies for Insulin Biosimilars, Interchangeables

As the cost of insulin continues to force some to ration their lifesaving drugs, the US Food and Drug Administration (FDA) on Monday released new draft guidance to help sponsors bring insulin biosimilars and interchangeable products to market more quickly.

The 8-page draft offers an update to FDA’s thinking on comparative clinical immunogenicity studies and whether they are necessary to support the licensure of proposed biosimilar and interchangeable insulin products for those with Type 1 or Type 2 diabetes.

Although no companies have publicly announced their intention to win approval for an interchangeable insulin product, this guidance, along with interchangeability guidance from May, should help speed their journey to market.

Previously, FDA explains, the agency took the position that data from a comparative clinical immunogenicity study would likely be needed to evaluate the potential risk and clinical impact of immunogenicity of proposed biosimilar and interchangeable insulin products.

“In this guidance, FDA describes its updated thinking that, generally, if a comparative analytical assessment based on state-of-the-art technology supports a demonstration of ‘highly similar’ for a proposed biosimilar or interchangeable insulin product, there would be little or no residual uncertainty regarding immunogenicity; in such instances, the proposed biosimilar or interchangeable insulin product, like the reference product, would be expected to have minimal or no risk of clinical impact from immunogenicity,” the draft says. “In such instances, a comparative clinical immunogenicity study generally would be unnecessary to support a demonstration of biosimilarity or interchangeability.”

As part of its reasoning behind its scientific thinking on a “lack of clinical impact of immunogenicity with insulin,” the draft cites a revised guideline from the European Medicines Agency in 2015, which said that it no longer recommends a clinical immunogenicity study to support a biosimilar marketing application.

FDA also points to “decades of clinical experience with approved insulin products, including the lack of a correlation between immunogenicity and safety or effectiveness as reflected in approved product labeling for insulin products.”

But there may be some limited cases where immunogenicity studies would be required. FDA adds that a comparative clinical immunogenicity study “may be necessary to support licensure of a proposed biosimilar or interchangeable insulin product for which differences in certain impurities or novel excipients give rise to questions or residual uncertainty related to immunogenicity.”

The draft encourages sponsors to contact FDA’s Division of Metabolism and Endocrinology Products in the Office of New Drugs to discuss proposed development programs and to request a Biosimilar Biological Product Development meeting, as appropriate.

The guidance comes as on 23 March 2020, the approved new drug applications (NDAs) for insulin products will be “deemed to be licenses” and can then serve as reference products for proposed biosimilar and interchangeable insulin products.

Meanwhile, FDA held a public meeting in May on biosimilar and interchangeable insulins, noting how competition is currently limited to only three follow-on insulin products—Basaglar, Lusduna and Admelog—which have been approved since 2015. But interchangeable insulins are expected over the next several years.

And several senators in March called on FDA to tweak other guidance to speed up the marketing of new biosimilar insulin products. Insulin manufacturers, however, told a House committee in April that simply lowering the list price for insulin will not increase access.

Regardless, the cost of insulin in the US continues to rise. Rep. Mike Kelly (R-PA) noted that the average annual cost of insulin for a person with type 1 diabetes is $5,705, a 600% increase since 2001.

Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products

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