It is possible you might not have caught an obscure press release (see the press release at https://www.prnewswire.com/news-releases/biocon-biologics-and-civica-inc-collaborate-to-expand-insulin-aspart-access-in-the-united-states-302394010.html for more details) from March 6, 2025 released by Biocon Biologics Ltd. which had announced a deal with the U.S. nonprofit drug company Civica, Inc. for insulin aspart only.
Under the terms of that particular agreement, Biocon Biologics agreed to supply insulin aspart drug substance to Civica, Inc., who will use that drug substance to produce its own insulin aspart drug product at its "fill & finish" manufacturing facility in Petersburg, Virginia (located near the state capital of Richmond). Civica will commercialize that medicine for patients in the United States, "after completion of development work and clinical trials". The latter's insulin Biologics License Applications (BLAs) are complete, except that Civica (as well as Biocon) awaits FDA approval decisions which have yet to be rendered as I write this. When Civica announced on March 3, 2022 that it was entering the U.S. biosimilars insulin space, the company revealed it would procure the insulin aspart Active Pharmaceutical Ingredient (API) from a firm known as GeneSys Biologics (see http://dlvr.it/SL0QZV for the original news release). Now, it has a new supplier, but [so far] only for insulin aspart.
In fact, while FDA finally approved Sanofi's biosimilar copy of insulin aspart on February 14, 2025 (catch my coverage of that at https://blog.sstrumello.com/2025/02/fda-approves-merilog-insulin-aspart.html for more), becoming the first biosimilar insulin FDA rendered a decision on in over three years, that lead me to question the reason FDA has a substantial backlog of insulin biosimilars which it has not yet rendered decisions on (see https://blog.sstrumello.com/2025/01/ask-fda-why-arent-insulin-biosimilars.html for my coverage of that).
Let me add that we are now more than halfway through 2025, and FDA has approved only one insulin biosimilar, and yet we know at least ten others are pending from Sandoz/Gan & Lee, Lannett Company/HEC, Amphastar Pharmaceuticals/ANP as well as Civica and whomever the company procures the insulin APIs from. Those include more biosimilars of glargine, aspart and a few of lispro. And, we know another three more are a few years behind those, including three from Meitheal Pharmaceuticals/THDB (which has copies of glargine, aspart and lispro in development). Originally, I presumed some of the delays were attributed to worldwide Covid-19 lockdowns, but there are hints of more problems at FDA and potentially with some of the companies developing insulin biosimilars more broadly.
The reason the March 6, 2025 news release from Biocon and Civica on insulin aspart was so surprising is because when Civica first announced that it intended to sell biosimilars of insulin glargine, insulin aspart and insulin lispro (to be sold at a price of no more than $30/vial or $55/box of five prefilled insulin pens), is because when Civica (along with Breakthrough T1D/JDRF) made the original announcement about three years earlier (back on March 3, 2022) that Civica would be entering the biosimilar insulin business, Civica revealed that it would procure the insulin Active Pharmaceutical Ingredients for each from a Hyderabad, India-based biotechnology firm known as GeneSys Biologics, Ltd., but not from Biocon. One additional peculiarity is that the March 6, 2025 announcement was the agreement was only for insulin aspart, but not for the insulin glargine or for insulin lispro biosimilars.
The original 2022 Civica press release stated: "Civica has entered into co-development and commercial agreement with GeneSys Biologics for these three insulin biosimilars." You may read the company 2022 press release at https://www.businesswire.com/news/home/20220303005321/en/Civica-to-Manufacture-and-Distribute-Affordable-Insulin/ along with the concurrent JDRF (now Breakthrough T1D) press release at https://www.prnewswire.com/news-releases/jdrf-announces-support-of-civica-to-manufacture-and-distribute-low-cost-insulin-301495050.html, although I covered news about the 2022 announcement on my blog in a post found at https://blog.sstrumello.com/2022/03/civica-rx-were-entering-us-insulin.html for more details. Originally, I presumed FDA had a slight backlog which might be attributed to worldwide Covid-19 lockdowns, but I think because FDA collects user-fees from these companies, it has an obligation to render decisions (which it has not yet made), and it can use the user-fees which it collects to pay for the staff needed to make those decisions.
There is something else peculiar about the 2025 Biocon Biologics/Civica announcement on insulin aspart. On January 7, 2022, Biocon Biologics revealed to investors that the U.S. FDA had denied the company's insulin aspart application by issuing a Complete Response Letter (CRL). However, Biocon told investors "This CRL did not identify scientific issues with the product but referenced Form 483 observations (which are Inspectional Observations at the conclusion of a manufacturing facility inspection. It lists conditions or practices observed during the inspection that, in the investigator's judgment, may constitute violations of the Food, Drug, and Cosmetic Act or other relevant FDA regulations.) from a pre-approval inspection of their [Johor,] Malaysia facility." (see https://www.bioconbiologics.com/the-usfda-issues-a-complete-response-letter-for-the-biologics-license-application-bla-for-insulin-aspart/ for more). Still, in the three years since then, FDA did not move on any insulin biosimilars until its Valentine's Day approval of Sanofi's Merilog biosimilar of Novo Nordisk's Novolog. Three years, user fees, and no decisions? That strikes me as pushing the limits on decisions. Its not as if taxpayers are paying for the staff needed to make these decisions, the applicants are paying for that.
What this means is that effective as of March 6, 2025, Civica announced a new supply agreement for a Novolog biosimilar from a company which does not even have FDA approval to sell an insulin aspart biosimilar. But this could suggest that the biotech partner Civica originally announced an agreement with back in March 2022 known as GeneSys Biologics might be having some issues in replicating the insulin aspart molecule, effectively prompting the company to find a new supplier for that, and the supplier the company chose is Biocon Biologics (which does not yet have FDA approval to sell an insulin aspart biosimilar).
We should be asking whether Civica might have observed problems with GeneSys Biologics making copies of Novolog specifically, and sought to resolve that with a more experienced partner who had the ability to deliver. Remember: Biocon's aspart biosimilar was denied by FDA not for scientific reasons, but because previous citations by FDA at its Johor, Malaysia manufacturing facility had not yet been resolved. FDA won't approve any others until existing problems are fixed to its satisfaction.
So far, we have not yet heard any particular problems on copies of Lantus or Humalog, although if the partner cannot deliver on them all, that is not very reassuring. And, Civica might remain committed to its original contract with GeneSys Biologics on glargine and lispro suggesting that the main difficulties were with aspart.
Maybe. But there is a sense in the biotechnology industry that making copies of insulin analogues might be easier than it really is. That's where having a competent biotech partner can help, and also a partner which can manage those relationships.
Sandoz has a Chinese lab partner named Gan & Lee making its insulin biosimilars (catch some of my prior coverage HERE and HERE), and in 2023, Gan & Lee has regularly reported via LinkedIn when the company had submitted BLA's (Biologics License Applications) for glargine https://www.ganlee.com/detail/683.html, lispro https://www.ganlee.com/detail/690.html, and insulin aspart https://www.ganlee.com/detail/691.html. My impression is that even while Gan & Lee is based in China, Sandoz is managing its partners' development timeframes and milestones quite closely. And yet, FDA hasn't (yet) rendered any decisions on those, either.
We should demand that our lawmakers ensure the FDA makes some decisions. Covid is over, so excuses for not rendering those decisions is unacceptable and they have had several years to consider them.
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