Did you know that the U.S. Food and Drug Administration (FDA) has only approved TWO insulin biosimilars, both of which are copies of Sanofi's basal insulin branded as Lantus (insulin glargine)? Specifically, as of January 4, 2024, the only two FDA-approved biosimilar insulins are as follows:
1. Semglee (insulin glargine-yfgn, 100 Units/mL)
- Manufactured by Biocon Biologics Ltd. (originally sold by Viatris)
- FDA approved on July 28, 2021
2. Rezvoglar (insulin glargine-aglr, 100 Units/mL)
- Manufactured and sold by Eli Lilly & Company, Inc.
- FDA approved on November 30, 2022
Both biosimilars are copies of the exact same insulin (they're copies of Sanofi's Lantus) for which there is already considerable competition, and it is a basal-only (no biosimilar prandial insulins) insulin variety.
Biocon also had a Novolog (insulin aspart) biosimilar in development, but that received a "Complete Response Letter" (CRL) from the FDA, which meant it was denied until certain issues had been successfully resolved first. But a number of other insulin biosimilars are currently pending FDA approval decisions, including even more additional copies of Lantus (insulin glargine) from Civica/GeneSys Biologics, Sandoz/Gan & Lee, Lannett Company/HEC, Amphastar/ANP, as well as copies of Novolog (insulin aspart) from Civica/GeneSys Biologics, Sandoz/Gan & Lee, Lannett Company/HEC, Amphastar/ANP, and copies of Humalog (insulin lispro) from Civica/GeneSys Biologics and Sandoz/Gan & Lee are all currently pending FDA approval decisions. Meitheal Pharmaceuticals is several years behind the other five companies, but it has biosimilars of Lantus, Novolog and Humalog also in development. I documented their development periodically, including my coverage HERE.
I would remind my followers that there are also several other insulin copies approved as "follow-on" biologic medicines because they attained approvals under a different regulatory pathway with the FDA. These insulins were originally approved under the Federal Food, Drug, and Cosmetics Act (FD&C Act), hence the FDA refers to them as "follow-on" biologic medicines rather than actual biosimilars. These follow-on insulin copies include:
➔ Basaglar (insulin glargine injection, 100 Units/mL)
- Manufactured and sold by Eli Lilly & Company, Inc.
- FDA approved on December 16, 2014
➔ Admelog (insulin lispro injection, 100 Units/mL)
- Manufactured and sold by Sanofi-Aventis LLC
- FDA approved on December 11, 2017
Recall that Sanofi introduced its copy of Lilly's Humalog branded as Admelog (insulin lispro) as kind of retribution against Lilly for selling its first copy of Lantus branded as Basaglar. Sanofi has its own proprietary prandial insulin branded as Apidra (insulin glulisine injection, 100 Units/mL) and a copy of someone else's prandial insulin might appear as cannibalization, although the fact that Apidra was on next to no insurance company drug formularies suggests that was really not a problem.
Insulin Was Trapped in a "No Generic" Zone for Complex Historical Reasons, But That's Now Over
In spite of patent expirations, the regulation of insulin historically fell under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which allowed Eli Lilly & Co., Novo Nordisk, and Sanofi to avoid (and prevent) "generic" competition (insulin was a biologic regulated as a small-molecule drug). This changed with the passage of the Biologics Price Competition and Innovation Act (BPCI Act), a provision of the Patient Protection and Affordable Care Act (PPACA or ACA), signed into law on March 23, 2010. The BPCI Act allowed for the submission of a Biological License Application (BLA) for biosimilars (or interchangeable biological products) and mandated that certain biological products, including for insulin and human growth hormone must officially "transition" to being regulated as biologics under the Public Health Service Act (PHS Act).
However, for a decade, the FDA had failed to implement these legally-mandated changes until March 23, 2020, under the leadership of Scott Gottlieb. For at least 10 years after it became law, FDA did virtually nothing to enable it. Congress allowed a transition period of "up to 10 years", and the FDA took the entire 10 years to implement those changes. In effect, FDA had finally moved to recognize that any insulin approved under the FD&C Act would thereby be recognized as a biologic by FDA, hence be eligible for biosimilars in accordance with the PHS Act as well as the BPCI Act.
Hints of FDA Backlog on Insulin Biosimilars?
Here's the thing: Biocon Biologics told investors that the company had first applied with the U.S. Food and Drug Administration (FDA) to sell a copy of insulin glargine injection in 2017. We also know that application was filed under the 505(b)(2) pathway, and that product received FDA approval for its version of insulin glargine, branded as Semglee, on June 11, 2020. All told, that suggested that it required about three (3) years from start to finish to receive FDA approval. But we now know with certainty that other insulin copies have been pending FDA approval decisions for at least that long. For example, among the publicly-held (or, in the case of Lannett Company, formerly publicly-held) companies which have already revealed they have biosimilar copies of insulin glargine pending approval have given us some more information.
On November 26, 2019, Lannett Company, Inc. (which as noted, at the time, was still a publicly-held company whose stock ticker was "LCI") revealed in an SEC filing (see https://seekingalpha.com/filing/4715183 for the filing itself) that it had entered into a new collaboration and license agreement with HEC with respect to the development, commercialization and distribution of HEC's insulin glargine product. In the company's 2021 annual report filed with the SEC, Lannett said the following:
"Additionally, we are focused on advancing our biosimilar Insulin Glargine and Insulin Aspart pipeline products. We filed our Investigational New Drug ("IND") application for Insulin Glargine in December 2021 to commence our pivotal clinical trial. This trial is ongoing and top-line results of the study are expected to be available at the end of calendar year 2022 [see the Press Release for more]. We anticipate filing the BLA for the biosimilar Insulin Glargine in early calendar 2023 and a potential launch in calendar year 2024. The biosimilar Insulin Aspart pipeline product is expected to potentially launch in calendar year 2025. We believe leveraging our existing relationships to collaborate on new opportunities will enable us to further strengthen our pipeline."
Legally-Exempted Rebate Kickbacks Paid to PBMs Responsible for Insulin Price Inflation
Also, the byzantine rebate-contracting sales model promoted by largest Pharmacy Benefit Managers (PBMs) with their notorious "misaligned incentives" has been a major problem until quite recently. According to the Drug Channels Institute (DCI), the total value of manufacturers' gross-to-net reductions for all brand-name drugs in 2023 was a stunning $334 billion. Despite acknowledgement of the rebate problem from a Senate Finance Committee report on insulin prices, no meaningful legislation to change this broken dynamic had occurred until 2021 when Democrats in Congress passed the American Rescue Plan into law on a partisan vote (Congressional Democrats also passed the ACA which included the BPCI Act which formally legalized biosimilar medicines in the first place, and did so without a single Republican lawmaker voting with them on it).
The End of the Insulin "Legally-Exempted Rebate Kickback" Scheme?
Interestingly, the American Rescue Plan (ARPA) of 2021, also eliminated a cap on drug rebates which were payable to Medicaid, starting on January 1, 2024. Previously, Medicaid rebates had been erroneously (or maybe not?) capped at 100% of the Average Manufacturer Price (AMP), while legally-exempted rebate kickback-driven list price inflation was included in prices which Medicaid patients paid for insulin. With the elimination of this ceiling, suddenly drug manufacturers with older, heavily-rebated drugs such as insulin were required to pay all rebates exceeding 100% of the AMP if the drug prices rose faster than the rate of inflation to Medicaid (and because of PBM demands for ever-higher rebates, that applied to insulin for the benefit of "formulary exclusion" of any and all competing insulin products). This change required branded insulin manufacturers to actually PAY Medicaid, instead of receiving payments for having their medicines on the list of Medicaid covered medications, thereby incentivizing them to slash their drug list prices in order to avoid negative pricing consequences (see https://progressivepolicyinstitute.medium.com/are-we-on-the-cusp-of-a-new-drug-pricing-paradigm-fdf611c009b3 for details).
In addition, the Federal Trade Commission (FTC) took legal action on September 20, 2024, suing the largest PBMs over their role in distorting U.S. insulin prices (see https://www.ftc.gov/news-events/news/press-releases/2024/09/ftc-sues-prescription-drug-middlemen-artificially-inflating-insulin-drug-prices?form=MG0AV3 for more about the litigation, and https://www.ftc.gov/legal-library/browse/cases-proceedings/221-0114-caremark-rx-zinc-health-services-et-al-matter-insulin for the actual court filing), while leaving open the potential to also sue branded insulin manufacturers for their role in those market distortions.
Without reiterating a topic I've covered extensively in the past, suffice to say, the PBM rebate-contracting sales model for insulin now appears to be essentially dead for the insulin therapeutic category of drug.
However, there are some hints that the PBMs such as CVS Caremark (via a new unit which the company calls Cordavis; see https://www.prnewswire.com/news-releases/cvs-health-launches-cordavis-301908281.html for more info on Cordavis, and key rivals including both Cigna Evernorth/Express Scripts' PBM business which has a similar unit based in the pharma hub (LOL!) of the Caynan Islands known as Quallent Pharmaceuticals, while United Healthcare's Optum PBM has a similar unit it calls Nuvalia, and they may instead consider selling PBM-branded insulins [and/or store-branded in the case of CVS]), similar to what they are now doing with Humira (adalimumab) biosimilars today. Sandoz is one entity supplying one of Cordavis' deeply-discounted Humira biosimilars branded as Hyrimoz (adalimumab-adaz), and its relevant to acknowledge that presently, Sandoz/Gan & Lee also now has biosimilars of Lantus, Novolog and Humalog currently pending FDA approval decisions. Once approved. Cordavis, Quallent or Nuvalia could just slap their own label on Sandoz/Gan & Lee-made (or any of the others) biosimilar insulins.
FDA, Staffed Largely with Ex-Pharma People, Has Historically Been a Pharma/Biotech Ally, Often Working Against Patients on Issues (other than on safety/efficacy) to Advance Pharma Business Interests
However, the FDA has historically and knowingly obstructed progress and protected the interests of major insulin manufacturers. Notably, FDA took over a decade to implement the changes mandated by the ACA's BPCI Act, delaying necessary (and required) regulatory transitions. However, I suspect much of that was due to former Principal Deputy Commissioner of FDA Janet Woodcock's leadership. But Dr. Woodcock announced her planned retirement in November 2023, and since then, she has since been replaced with a woman named Namandjé N. Bumpus. It is unclear how Dr. Bumpus might re-prioritize or modify FDA operating procedures, but without the pro-pharma/biotech Janet Woodcock calling the shots at the FDA, change seems virtually inevitable.
More Potential Changes with a New Trump Administration?
Something else: a new think tank called "Paragon Health Institute" https://paragoninstitute.org/, founded by an adviser under Trump's first administration may help shape health policy under a new Trump admin (not that they have a real record of any meaningful accomplishment in health policy; look at its questionable response to COVID-19 as proof).
Paragon makes economic arguments for changes in health policy. In particular, Paragon founder Brian Blase is critical of what he calls "wasteful" expanded pandemic-era subsidies that have helped people buy insurance through the Affordable Care Act (apparently, corporate welfare is good, but welfare for U.S. citizens is bad in Paragon's view). He says those subsidies should be allowed to expire after 2025. However, given that the blueprint for the ACA was taken directly from the conservative Heritage Foundation (when that organization still did policy development), beyond eliminating subsidies or maybe trying to impose work requirements (a requirement which most recipients actually satisfy), it's hard to envision much more on that front they could actually do.
But it could potentially turn attention back on PBMs' role in inflating U.S. prescription drug prices, especially with such people (whom I admire) like Johns Hopkins' Ge Bai as a policy advisor to Paragon (see her bio at https://carey.jhu.edu/faculty/faculty-directory/ge-bai-phd for details).
Article source:
https://www.npr.org/2024/11/26/nx-s1-5183231/a-look-at-the-think-tank-that-may-shape-trumps-health-policies
That said, the FDA really appears to be delaying new biosimilar insulin approval decisions, having approved zero during the past few years in spite of having quite many applicants. Recall that in 2019, FDA had formally issued Draft Guidance for Biosimilar Insulin Makers intended to help facilitate the development of biosimilar insulin products, and yet FDA has not approved a new insulin biosimilar since 2022. Perhaps COVID-19 slowed things down for a year or two, but it is 2025 now. The FDA has had several years to work through any backlog. The holdup seems to be with the FDA itself, not with the applicants.
Let me also add that none of these are NEW molecules, they are copies of already existing molecules. As long as the applicants can satisfy the requirements the FDA outlined in its guidance, then we should be nagging our lawmakers on what the heck is taking so damn long?!
No comments:
Post a Comment