The importance of insulin competition cannot be overemphasized today. Prices for each types of insulin have lurched upwards. The first competitive version of insulin glargine was approved in the US in late 2015, and according to IQVIA data, it has gained 31% of the US market (as of Q4 2018). Yet, information on other types of insulin to be approved as biosimilar under development is very limited at the moment.
Insulin in Transition
Part of the reason may be the transitional nature of insulin approval. In March 2020, all follow-on insulin “copies” must be approved under Section 351(k) of the Public Health Act, rather than under 505(b)(2) of the Food, Drug & Cosmetics Act. All three approved follow-on insulins in the US (Basaglar®, Lusduna®, and Admelog®) entered the market as 505(b)(2) agents. Lusduna is no longer being marketed in the US by Merck because of limited revenue potential. This decision may have been influenced by the closer federal scrutiny on insulin price increases of late.
Some development is ongoing for new insulin competition, but these are currently limited to insulin glargine, vying for a slice of the Lantus® market. Mylan, Sandoz, and GC Pharma all have biosimilar insulins that have been approved elsewhere in the world, Mylan and Biocon had first applied for FDA approval through the 505(b)(2) pathway in September 2017; they received a rejection due to manufacturing plant problems in June 2018. Current details are not known. Admelog® remains the only follow-on version of insulin lispro available or in development. Any FDA filing that remains unapproved by the transition date will be converted to a 351(k) biologic licensing application, subject to an entirely different level of requirements. It may be that prospective biosimilar insulin makers are awaiting the passage of the transition date before beginning the FDA filing process.
BR&R requested information from the FDA as to the number of biosimilar insulin clinical development programs currently in their system. A spokesperson for the FDA’s Center for Drug Evaluation said they couldn’t disclose any information about current biosimilar clinical development programs (even the number). Without this information, the chart below was based on publicly available information, and this is thin indeed, considering the various forms of rapid and intermediate-acting insulins that will be subject to biosimilar competition.
TABLE: INSULIN VERSIONS CURRENTLY APPROVED OR UNDER DEVELOPMENT
| Company | Insulin Type | Brand name | Status |
| Sanofi Aventis | Insulin lispro | Admelog | Approved by the FDA, Dec 2017, marketed |
| Samsung Bioepis/Merck | Insulin glargine | Lusduna | Approved by the FDA, withdrawn in Oct 2018 |
| Lilly | Insulin glargine | Basaglar | Approved by the FDA, Dec 2015, marketed |
| Mylan/Biocon | Insulin glargine | Approved in EU and Australia March 2018; 505(b)(2) application rejected June 1, 2018 | |
| GC Pharma | Insulin glargine | Launched in South Korea Nov 2018 | |
| Sandoz | Insulin glargine | Signed agreement with the Chinese company Gan and Lee to supply Sandoz with insulin | |
| Lannet | Insulin glargine | Phase 1 trial ongoing |
Data gathered from multiple sources.
The Insulin Authorized Generic
Also of direct impact to potential biologic makers, is the action taken by Lilly recently, when it launched a 50% price cut for its popular Humalog brand, under the banner of an “authorized generic.” This enabled Lilly to continue selling its Humalog brand, while getting a jump on the lower-cost market as a separate generic. This raises another separate interesting point: If Lilly outsources the production of the lower-cost version of Humalog, does this not imply that it is subject high risk of lot-to-lot variation? This is an issue at the heart of biosimilarity. Yet, the product is still covered by the FD&C Act; can this insulin version still be construed as a generic? On the other hand, if Lilly manufacturers this agent itself, since the molecule is the same as the brand, by the same manufacturer, a generic characterization of this biologic may still be possible. We digress….
For long-time insulin makers like Lilly, Novo Nordisk, and Sanofi Aventis, this action can easily be replicated for all of their insulin products (outside of offering greater rebates to counter biosimilar competition). So far, Lilly was the only one to take this action; this was not in response to potential biosimilar competition, but in direct response to the federal and legislative call for lower-cost insulin.
Insulin Interchangeability?
When the FDA Commissioner Ned Sharpless released the final interchangeability standards for biologics, he pointed to insulins specifically: “An interchangeable insulin product may be substituted at the pharmacy, potentially leading to increased access and lower costs for patients. For chronically used biologic medications patients get at the pharmacy, such as insulin, the ability to have a licensed interchangeable that can be substituted at the pharmacy without the intervention of the prescribing health care professional—much like how generic drugs are routinely substituted for brand name drugs—could be integral to the success of reducing drug prices for patients.”
The FDA spokesperson provided BR&R the following statement: “Given our long experience regulating insulin products, and high interest among sponsors regarding the development of biosimilar and interchangeable insulin products, we’re confident that once interchangeable insulins are approved and available on the market they will bring new competition to the insulin market without compromising safety and effectiveness, and potentially result in more affordable treatment options being available to patients with diabetes.”
Far more clinical development in biosimilar insulin must be underway to support the competition necessary for that to happen. Perhaps, the interchangeability guidelines release will spur more interest in the biosimilar insulin area. However, if clinical development is lagging in biosimilar versions of other popular forms of insulin (e.g., short- and intermediate-acting forms), then insulin price competition will be many years from becoming a reality.
