FDA Approves Merilog (insulin-aspart-szjj) as First Prandial Insulin Biosimilar Product for Treatment of Diabetes

My followers might recall my groundbreaking January 8, 2007 article (see that at https://blog.sstrumello.com/2007/01/business-of-diabetes-real-story-behind.html for more) which followed a long discovery process which began back in 2006 based upon a very simple question: the patents on biosynthetic insulin had expired, so why did Americans have no generic products to help reduce prices?

As it turned out, the answer was unnecessarily complicated. It was complicated by design from entities who benefitted from not having generic or biosimilar competition. And, I don't mean pharma as such, but from vertically-integrated (with commercial healthcare insurance companies) Pharmacy Benefit Managers (PBMs) who were behind the scenes, demanding ever-larger legally-exempt rebate kickbacks for preferred formulary positioning. Those demands for bigger rebates led to list-price inflation.

There were a variety of other factors involved, including the fact that insulin was the very first-ever biologic medicine which was approved back in 1982, but it had been regulated as a small-molecule "drug" whose manufacture just so happened to be regulated as the manufacture of a biologic medicine. Also, Federal lawmakers had not explicitly legalized copies of biologic medicines until Democrats in Congress (not a single Republican lawmaker voted for it) passed the Biologics Price Competition and Innovation Act (BPCIA) in 2019, which was a key provision of the Patient Protection and Affordable Care Act (aka Obamacare) which explicitly legalized biosimilar medicines in the first place, including outlining of procedures which must be followed by pharma to attain FDA approval.

But beyond that was the uncomfortable reality that FDA policy had still failed to recognize insulins which had originally been approved by FDA as small molecule "drugs" (which were manufactured as biologic medicines) were even eligible for biosimilar competition, and the FDA took nearly a decade after the Patient Protection and Affordable Care Act became law before it finally implemented policies to do that. It was under former Trump FDA Chief Scott Gottlieb that FDA finally did that in spite of being repeatedly prompted by lawmakers to do so, and only because the FDA itself had failed to implement those policies for nearly a decade. On the latter, it is believed that Lilly, Novo Nordisk and Sanofi had quietly encouraged their former colleagues then working at FDA to keep delaying those policies in an effort to prevent any competition from coming to market for as long as possible.

That said, what I originally referred to as "generic" (FDA referred to those "follow-on" biologics, which subsequently became known as biosimilars approved under a slightly different regulatory pathway at FDA) insulins eventually happened anyway. 

Originally, the "follow-on" biologic insulins came to market first because FDA's own dysfunctional policy enabling biosimilars had not yet been formally implemented. Once FDA finally got its $#!+ together and implemented policies required under U.S. law, that finally enabled true biosimilars to come to market.

Which brings me to last week's FDA announcement (see https://www.fda.gov/news-events/press-announcements/fda-approves-first-rapid-acting-insulin-biosimilar-product-treatment-diabetes for the news release) that FDA had officially approved the first biosimilar copy of Novolog (insulin aspart injection, 100 units/mL) to be made by Sanofi Aventis LLC whose trade name will be known as Merilog (insulin aspart-szjj). Observe the color scheme used for Merilog: orange, which is the same color Novo Nordisk uses in boxes containing Novolog.

The FDA package insert (see https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761325Orig1s000lbl.pdf for the insert itself) for Merilog includes proposed images (Sanofi will use the color orange also used by Novo Nordisk for Novolog for the newly-approved Merilog product, rather than the maroon color which it uses for the follow-on biologic branded as Admelog). The image is of the proposed box containing a 10 mL vial.

Sanofi already sells a copy of Lilly's Humalog (insulin lispro injection, 100 units/mL) sold under the brand/trade name "Admelog" which was approved by FDA on December 11, 2017 (see the FDA news release on that at https://www.fda.gov/news-events/press-announcements/fda-approves-admelog-first-short-acting-follow-insulin-product-treat-diabetes for more). 

However, unlike Admelog, Merilog has been approved as a "biosimilar", rather than as a "follow-on biologic" medicine. The differences are that: a) the approval pathway at FDA was different for Admelog vs. Merilog, and b) as a "biosimilar", Sanofi could theoretically later seek a designation as "interchangeable" from FDA which would enable pharmacists to switch to Merilog without the prescribing doctor's permission unless the doctor designates the prescription "Prescribe as Written" or "No Substitution Permitted" on the prescription. The FDA approval of Merilog also brings a long-standing delay at FDA to a close. The FDA had only two previous insulins which were approved as "biosimilar" drugs, specifically Semglee (insulin glargine-yfgn) which was first approved by the FDA in June 2020 (and subsequently received approval as an "interchangeable biosimilar" to innovator Sanofi Lantus on July 28, 2021), and a second copy of Lantus made by Eli Lilly & Company, Inc. which is sold under the trade name Rezvoglar (insulin glargine-aglr) which received FDA approval in December 2021. This means that for three years, FDA had not rendered any decisions on biosimilar insulins, although truthfully, Covid-19 shutdowns delayed many FDA decisions.

To my knowledge, Sanofi only sells vials and Solostar prefilled pens of insulin, but it does not currently sell 3 mL cartridges of insulins as both Novo Nordisk and Lilly do (the latter sells pen cartridges only for certain varieties of prandial insulin analogues only) which would work with refillable, smart insulin pens such as Medtronic's InPen which automatically logs each dosage given with the pen enabling patients to easily track insulin on-board.

Of course, if PBMs are involved, they will just non-medically switch patients anyway by disregarding the FDA designation and calling the products "therapeutically equivalent" in order for the PBM to try and collect legally-exempted rebate kickbacks (although in 2023-2024, Lilly, Novo Nordisk and Sanofi all effectively opted-out of the rebate-contracting sales model for the insulin therapeutic class of drugs).

There is also a photo of the Solostar prefilled insulin pen on the package insert given to the FDA. Of note is that under Section 16, which is entitled "HOW SUPPLIED/STORAGE AND HANDLING", and more specifically under Section 16.1, where it describes "How Supplied," it says that MERILOG (insulin aspart-szjj) injection 100 units/mL (U-100) is available as a clear and colorless solution in one 10 mL multiple-dose vial per carton (which is assigned the NDC # 0024-5927-00),  or in five 3 mL single-patient-use SoloStar prefilled pens per carton (which is assigned the NDC # 0024-5928-05). It also adds "The MERILOG SoloStar prefilled pen dials in 1-unit increments" (rather than 1/2 unit increments).

With all that said, while Novolog will experience its first biosimilar copy, there are quite a few others, most of which are pending FDA at this very moment. As a reminder, those could be from (which I documented them in a previous post found at https://blog.sstrumello.com/2023/09/another-three-biosimilar-insulins.html):

• Biocon Biologics, Inc. (in Feb. 2023, FDA denied Biocon's aspart biosimilar application with a Complete Response Letter (CRL), indicating that Biocon first needed to address some deficiencies which FDA had cited before FDA would approve it, and Biocon told investors that it intended to fix those things)
• Sandoz/Gan & Lee 
• Civica, Inc.'s CivicaScript PBC operating unit/GeneSys Biologics
• Amphastar Pharmaceuticals/ANP
• Lannett Company, Inc./YiChang HEC ChangJiang Pharmaceutical Co., Ltd. [HEC]

About five years behind those companies' aspart biosimilars, a sixth copy from Meitheal Pharmaceuticals/Tonghua Dongbao Pharmaceutical Co. Ltd. is also in development, but as noted, that Chicago-based company is a few years behind the others in terms of development.

These just so happen to be the publicly-held (or, in the case of Lannett Company, a formerly publicly-held) companies I know about. It's possible there could be others based outside the U.S. which also intend to make Novolog biosimilar copies as well.

As for Novo Nordisk, Inc. (the U.S.-based subsidiary of Denmark-based Novo Nordisk A/S whose headquarters are in Plainsboro, NJ [which borders Princeton]), my expectation is that the company is likely to simply discontinue (or "retire" in company parlance) the original insulin aspart and focus exclusively on its slightly-improved Fiasp (the name derived from "Faster Insulin ASPart") which works marginally faster thanks to the addition of vitamin B3 or B6 which still retains patent exclusivity for the time-being. Novo Nordisk has retired more than a dozen still-efficacious insulin varieties over the past 25 years because they no longer enjoyed Intellectual Property (IP) rights. Novolog is merely the latest.

The difference this time around is unlike in the past when patients were forced to "upgrade" to Novo Nordisk's newest, patent-protected insulin varieties, if patients wish to keep using original insulin aspart, they will likely be able to use Sanofi's Merilog or any of the others currently pending FDA approval decisions.

What Crains Modern Healthcare Says about Rep. Dr. Greg Murphy (R-NC) and how the FTC should break-up United Healthcare

Last October [2024], I shared how I harnessed AI tools to retrieve article content hidden behind a paywall. In particular in my post about the drama behind the change in CVS Health's CEO (see my post at https://blog.sstrumello.com/2024/10/what-cvs-health-ceo-shuffle-has-to-do.html), I found that Crain's Modern Healthcare was the publication, and I found using ChatGPT (rather than Microsoft Bing Copilot or Google's Gemini) worked most effectively for stripping html formatting out of the article content in a matter of seconds.

Well, I'm doing it again, this time I am returning to an article published in Crain's Modern Healthcare, and an article published on January 28, 2025, specifically one about a conservative named Rep. Dr. Greg Murphy (R-N.C.) who wants to rein in federal spending, but he believes that lawmakers should encourage the Federal Trade Commission (FTC) to consider studying United Healthcare Group, and whether it might be appropriate to break that organization up. Read below for complete access to the article.

Bust up Big Insurance, curb Medicare Advantage, Republican says
By Michael McAuliff, Crain's Modern Healthcare
January 28, 2025

Rep. Dr. Greg Murphy (R-N.C.) is a conservative who wants to rein in federal spending, and gets why big programs such as Medicaid and the health insurance exchanges make attractive targets for spending reductions. He's also a urologist and former hospital executive who has seen the value of access to healthcare firsthand.

That's why the trillions of dollars in healthcare cuts House Republicans are considering give him pause, even though he agrees with the direction House Speaker Mike Johnson (R-La.) and President Donald Trump want to take the federal government, Murphy said in a wide-ranging interview last week.

Rather than simply rip massive amounts of money from major programs, Congress should be more focused and creative, said Murphy, who sits on the Ways and Means Committee, which has big influence over health policy because of its jurisdiction over Medicare.

Murphy draws on his experience inside the healthcare system to offer more nuanced, and perhaps unexpected, solutions.

The three-term congressman, whose district stretches from the Atlantic coast to Greenville, thinks lawmakers need to look at cracking down on overspending under Medicare Advantage, busting up vertically integrated healthcare conglomerates such as UnitedHealth Group and increasing doctor pay.

Murphy, who still sees patients, is particularly attentive to how new laws would affect hospitals, he said. Prior to entering electoral politics in 2015, Murphy was chief of staff at Vidant Medical Center in Greenville, the flagship hospital of University Health Systems of Eastern Carolina, known as ECU Health.

"First and foremost, I care about the patient in front of me, and that means access, that means affordability, that means the highest-quality care — period," Murphy said.

What it takes to achieve that, Murphy said, is "making sure that people who actually take care of the medicine or take care of the patient are taken care of — the doctors, the nurses, the physician assistants, nurse practitioners, everybody."

Trump tax cuts, Medicaid cuts

That would necessitate a tricky balancing act if Republicans remain committed to renewing the tax cuts on wealthy households and corporations Trump enacted in 2017, and which are due to sunset at the end of the year.

The Ways and Means Committee and Senate Finance Committee will take the lead on that effort. Murphy is a member of the Ways and Means Committee's and Veterans' Affairs Committee's health subcommittees and belongs to the GOP Doctors Caucus, the Primary Care Caucus, the Academic Medicine Caucus, the Kidney Caucus and the conservative Republican Study Committee.

Extending these tax policies would increase the federal debt by $4.6 trillion over 10 years unless Congress offsets the lost revenue with spending cuts or other tax increases, according to the nonpartisan Congressional Budget Office.

Murphy does not dismiss the substantial budget cuts that his colleagues are discussing. That includes taking $2.3 trillion out of Medicaid, which hospitals caution would have devastating consequences, particularly in rural areas like those Murphy represents.

From Murphy's point of view, there are savings to be found in healthcare programs, but lawmakers need to approach them with a scalpel, not an ax. Whatever Congress does, it must take into account how its policies impact patients and providers, not just the federal balance sheet, he said.

To reduce Medicaid spending, Murphy said, Congress should target providers that overtreat patients and bill the government and take steps to bring down enrollment. Murphy cited anecdotes of individuals he believes don't qualify for benefits but are enrolled, and pointed to work requirements as a means to shift people off Medicaid and onto job-based health plans.

"You're on Medicaid and you walk in the room fine, then there's somewhere you can work and get insurance," Murphy said. "There's plenty of savings that goes on with that. At the same time, I'm adamantly opposed to cutting anything that keeps our critical access hospitals, our rural hospitals alive."

'Cut the head off the snake'

Murphy also counts himself among the growing number of GOP lawmakers who look askance at the role of large, for-profit companies in the healthcare system. Rampant prior authorization demands, lack of competition among pharmacy benefit managers and other aspects of the health sector are ripe for change, he said.

"What they're doing is they're denying care to patients, making more expensive care to patients," Murphy said. "I don't mind profit. I don't. I'm very much a capitalist. But when you, on the end result, are not fulfilling your duty to allow me as a physician to take care of patients, to have them get the care that they need, and [when that's] in the face of unexplainable record profits, there is something wrong — morally, ethically and possibly legally."

UnitedHealth Group is the biggest offender, Murphy said. He would like the Trump administration to carry out the work the Federal Trade Commission began under President Joe Biden. That would ultimately lead, he said, to the disintegration of the company, which comprises the largest health insurer by membership in UnitedHealthcare, the second-largest PBM by market share in OptumRx and the largest employer of physicians in Optum.

Taking a hard line against UnitedHealth Group would make the rest of the industry fall in line, Murphy said.

"So many of the other companies do the same exact thing, but sometimes you have to cut the head off the snake to send a message that what they're doing is wrong — I truly believe immoral," Murphy said.

'Hundreds of billions' from Medicare Advantage

When it comes to Medicare Advantage — in which UnitedHealthcare is second in market share to Humana — Murphy and some other Republicans see too much profiteering and too much pressure on providers, even though the party has strongly supported the privatized version of Medicare for decades.

Medicare Advantage now covers more than half of Medicare-eligible people, a mark of success for the program created under President Bill Clinton and Speaker Newt Gingrich (R-Ga.) in 1997.

But what Murphy sees, he said, is far too many claims denials, shady marketing tactics and gaming the program to generate additional revenue. That means there's money on the table, he said.

"The upcoding is disastrous, and that will be hundreds of billions of dollars in savings," Murphy said. "These insurance companies using Medicare Advantage are taking advantage of the system, they're also upcoding and not providing the care."

Murphy is more traditional when it comes to the Affordable Care Act of 2010, in that he opposed it from the start. But enrollment in the law's health insurance exchanges surged to more than 24 million this year, spurred by enhanced premium tax credits Biden enacted that expire at the end of the year.

Like a number of other Republicans who are not fans of the law, however, Murphy did not just say the more generous subsidies should be allowed to disappear. He suggested that the tax credits are too generous and need to be rolled back. For instance, he noted that in rare cases families that earn up to $600,000 could qualify for at least some financial assistance if their medical expenses are more than 7.5% of their income.

"That's absurd, and so I think we'll take a good look at this," Murphy said. "We want our working poor, especially, to be able to get good, accessible healthcare. But again, we overshot," he said. "The adults are back in the room, and the adults are needing to balance the checkbook."

Raising doctor pay

At the same time, GOP lawmakers including Murphy have priorities that would require new spending. For instance, Murphy supports boosting Medicare reimbursements to physicians, who bemoan that rates haven't kept up with rising expenses. In December, Congress came close to undoing a 2.9% Medicare pay cut for this year but failed to see it through.

A new physician reimbursement system would cost many billions of dollars, but that's worth keeping doctors from leaving medicine or selling their practices to private equity investors or health systems, Murphy said. "The latter two are not the best care. It's less efficient, more expensive," he said.

The end-of-year spending package that didn't include a pay hike for doctors expires in March, and lawmakers are working on a "continuing resolution," or CR, to fund the government through the end of fiscal 2025. If the new bill doesn't address Medicare physician reimbursements, Murphy will oppose it, he said.

"I've had a guarantee from the Trump transition team to the speaker that this gets dealt with in the next CR," Murphy said. "it will be a red line for me, unless it gets dealt with. I cannot see the destruction of private practices."

URL for this article (mostly hidden behind paywall):
https://www.modernhealthcare.com/politics-policy/greg-murphy-medicaid-cuts-medicare-advantage

Using Diabetes as a "Disability" to Claim Certain Benefits

You've likely heard of stories of people who use diabetes as an excuse to avoid waiting in long queues at Disneyland or Disney World attractions. It's not as if diabetes impairs one's ability to wait in line at a crowded, hot theme park. I have also never tried to use diabetes as an excuse to get priority boarding on an airline flight, although some people attempt that. 

But, there are a few "perks" of having a disability such as diabetes, which is what today's post is about.

On October 23, 2023, an article written by April Hopcroft was published by diaTribe News entitled "How To Get a Free Lifetime National Parks Pass" (see https://diatribe.org/lifestyle/how-get-free-lifetime-national-parks-pass for the source). The article was published in late October, and most people tend to visit National Parks during the summer, so it might not have received as much coverage it really deserved to get at the time as if it had been published in the springtime when people plan their summer vacations.  

One of the perks of living with Type 1 or Type 2 diabetes is you can receive a free National Parks pass. It means that patients with diabetes have the ability to get a FREE lifetime National Park Pass enabling them to access various parks and recreation sites across the U.S. The free-if-you-have diabetes pass is called an "Access Pass", and it is a free, lifetime version of the National Park Service's (NPS) "America the Beautiful Pass", which ordinarily costs Americans $80 per year. 

The diaTribe article said that the National Park Access Pass provides free access to over 2,000 federal recreation sites, from iconic National Parks – such as Yellowstone, Grand Canyon, and Yosemite. 

Of course, national parklands are most abundant in the Western United States where there are vast tracts of land and the states are physically large but many are sparsely-populated. 

But even those of us living in places like the East Coast have access to the stunningly beautiful Cape Cod and/or Fire Island National Seashores. In Wisconsin, we have what's referred to as the "National Lakeshore" along Lake Superior which is known as Apostle Islands. On top of that, other national parklands also include historical sites, battlefields, and other landmarks such as Manhattan's Stonewall Inn, now considered to be the birthplace of the gay rights movement in 1969 but it was originally a mafia-owned bar which served gay clients. 

A few years ago, after a trip to Phoenix, Arizona, my spouse and I extended our stay to make a trip to the Grand Canyon which I'd never seen in-person. The Grand Canyon National Park is actually much closer to Las Vegas, Nevada than it is to the state capital Phoenix, but there are plenty of bus tour operators in Phoenix, so I did not even have to drive. I was thrilled to have the opportunity to see what is arguably one of the jewels of the U.S. National Park Services, and because our visit was in early May, we avoided the typical summer traffic jams at the park entrances plus the weather was very pleasant at that time. 

Similarly, my sister and brother in-laws bought a house where they're likely to retire on Cape Cod, and we visited them off-season so getting into the Cape Cod National Seashore was not an issue because those parklands were not officially open at the time (and, it was too cold to sunbathe at the beach), but it's nice to avoid paying an entrance fee of $20 to $35 when it IS beach season. 

Like anything FREE, getting a free National Park Access Pass (the paid version costs $80/year and is known as the "America the Beautiful Pass") is not always easy. 

Qualified individuals can go to a National Park Visitor Center and get their free pass there, but that also means waiting in line in a Visitor Center rather than enjoying the beauty of our National Parks. I'm the type of person who likes to have those things already taken care of upon my arrival. The last thing I want to do is arrive trying to get a free pass only to find I would only be able to use it for my next visit.

There are two requirements for getting a FREE lifetime National Park "Access Pass" (the card itself has the internationally recognized handicap symbol on the lower left side of the card featuring the outline of an individual in a wheelchair). The National Parks" Access Pass" is pictured below.

I liked the diaTribe article, but found it a bit difficult to follow its instructions to get one. So I'll try it again with better instructions.

To apply, you must submit an application form which is available at a National Park Visitor Center, or the form is also available online at https://prod-ibis-green.s3.us-west-2.amazonaws.com/s3fs-public/access_pass_application.pdf and then complete it (which is straightforward enough), sign it, date it and then either mail it to the USGS (the U.S. Geology, Geophysics, and Geochemistry Science Center) processing center in Denver, Colorado (the address is listed on the application form), or you may hand it to a park ranger working at the National Park Visitor Center along with the other required proof of your eligibility. Alternatively, perhaps the easiest way is to submit the application (along with relevant proof of eligibility) online at https://store.usgs.gov/access-pass. 

The documentation of eligibility consists of the following items:

First, a signed, dated and completed application form (see above).

Second, applicants must provide photo identification to verify that they are a U.S. citizen (or lawful permanent resident), which could include any of the following:  

• A U.S. State (or Territory)-issued Driver's License, Identification Card, or Birth Certificate
• A U.S. Passport or U.S. Passport Card
• A Permanent Resident Card (Green Card)

Photocopies (or scanned digital copies if you apply online) of a valid passport, driver's license or valid state-issued photo identification card are accepted with the application.

Third, you must also provide proof of eligibility that you have a legally-defined "permanent disability" which includes diabetes (either Type 1, Type 2 or idiopathic diabetes; note that gestational diabetes is not a permanent condition and is therefore ineligible).

In order to qualify and apply, applicants must show any ONE of the following forms of evidence of disability: 

1. A statement by a licensed physician on their official letterhead who treats someone with diabetes noting that the person has a permanent disability of diabetes, and that it limits one or more aspects of their daily life, and the nature of those limitations.
   
   Eligibility applies to U.S. citizens (or lawful permanent residents) with permanent disabilities, and diabetes is considered under the law to be a disability because "it substantially limits the function of the endocrine system," according to the American Diabetes Association (see https://diabetes.org/advocacy/know-your-rights/is-diabetes-a-disability for more).
   
   I actually advocated and pushed in order to make sure that diabetes was included on the list of conditions defined under the Americans with Disabilities Act (ADA) back in 1990. I did so under the American Diabetes Association which was pushing to include diabetes on the list, and when then President George H.W. Bush (the now deceased successor to President Reagan) was in office, who signed that into law. Originally, diabetes was not included on the list, but the ADA and patient advocates successfully pushed to include the "invisible disability" of diabetes on that list.
   
   
2. A document issued by a federal agency, such as the Veterans Administration, Social Security Disability Income, or Supplemental Security Income.
   
   
3. A document issued by a state agency, such as a vocational rehabilitation agency.

In my case, the only one I can get is to ask my endocrinologist to write a letter on their letterhead to satisfy item #1 above as proof of disability, and address "To whom it may concern" stating that I have a permanent disability of autoimmune Type 1 diabetes mellitus (T1D) which substantially limits the function of my endocrine system. The nature of those limitations is that Type 1 diabetes mellitus requires uninterrupted access to an exogenous supply of insulin, as well as regular and continuous monitoring of my blood glucose levels in order to maintain euglycemia.

With that, I intend to submit an application to receive a FREE lifetime National Park "Access Pass" which entitles me to free entrance to any of our National Parks. Because I intend to apply online or by snail-mail, while the "Access Pass" itself is completely free, but they do charge $10 for processing and shipping of the card itself.

PBM Reform Under a New Trump Admin: A Clash of Titans and a Broken System Badly in Need of Reform

My followers might recall that back in 2022, I first noted Ge Bai. She had been interviewed by a podcast episode which I shared, you can catch my coverage of a podcast interview with her at https://blog.sstrumello.com/2022/12/podcast-recommendation-relentless.html for more (including where you can listen to her interview with the Relentless Health Care Value podcast). Be forewarned: Ge Bai has a very strong Chinese accent, hence I found it occasionally difficult to follow what she was saying. Fortunately, on podcast interviews, you can rewind things to listen again.

You may visit Ge Bai's faculty page at Johns Hopkins University at https://publichealth.jhu.edu/faculty/3887/ge-bai for more details. Also, her LinkedIn page can be found at https://www.linkedin.com/in/ge-bai-16945370/. That said, on November 26, 2024 on NPR's radio show "All Things Considered", it was revealed that Ge Bai had joined a Washington think-tank known as the Paragon Health Institute https://paragoninstitute.org/ as a policy advisor. See the NPR story mentioning that at https://www.npr.org/2024/11/26/nx-s1-5183231/a-look-at-the-think-tank-that-may-shape-trumps-health-policies for more about that.

The role of Pharmacy Benefit Managers (PBMs) in the U.S. healthcare system has become a contentious battleground, pitting powerful industry players against each other and leaving patients and taxpayers caught in the crossfire. This complex issue recently reignited when Ge Bai, an accounting professor at Johns Hopkins University and a leading voice in U.S. healthcare finance, published an article in Forbes titled "Blame the Game or the Players: Regulating Pharmacy Benefit Managers" (see her article at https://www.forbes.com/sites/gebai/2024/12/31/blame-the-game-or-the-players-regulating-pharmacy-benefit-managers/ for more).

Bai's analysis, which delved into the intricate web of relationships between drug manufacturers, insurers, and pharmacies, quickly drew fire from the billionaire entrepreneur Mark Cuban, who runs Mark Cuban Cost Plus Drug Company. On the social media platform BlueSky, Mark Cuban launched a scathing critique (see https://bsky.app/profile/mcuban.bsky.social/post/3lg4gm47ryk2b for his comment):

"Awful piece. PBMs choose to abuse the system. Generic prices are cheaper in the US than in many countries with universal healthcare. She protects PBMs rather than asking why they exist and whether pricing could be negotiated independently."

Cuban's sharp words ignited a broader discussion about the role and impact of PBMs. Antonio Ciaccia of 46brooklyn Research offered a [slightly] more nuanced perspective:

"Sure, some meh defensive stuff [about PBMs] in there, but broad[er] theme is on point: much of PBM games stem from poor system design that begs for their use. Incentivize lower manufacturer and pharmacy sticker prices (repeal safe harbor, no MFN pharmacy contracts, cost plus), and PBM necessity drops like a rock."

Ciaccia's response highlighted a critical point: the current U.S. prescription drug distribution system, with its convoluted "misaligned" incentives and complete lack of transparency, arguably necessitates the existence of PBMs. However, he argues that a fundamental overhaul of the system, with measures including repealing the "safe harbor" exemption from the federal antikickback statute, and prohibiting PBMs' "Most Favored Nation" contracts with retail pharmacies, could significantly reduce the need for these intermediaries going forward.

This debate underscores the underlying complexities of the U.S. healthcare landscape. Enter Paragon Health Institute, a new think tank founded by Brian Blase, a former Trump healthcare policy advisor. Paragon, which aims to eliminate what it considers "wasteful" government incentives, has quickly gained influence within the current administration. That was chronicled by NPR in a short segment which ran on the program "All Things Considered" in late November 2024 (listen below or by using the link, or read it at https://www.npr.org/2024/11/26/nx-s1-5183231/a-look-at-the-think-tank-that-may-shape-trumps-health-policies for more).

Blase, a vocal critic of government intervention in U.S. healthcare, has advocated for policies that he asserts prioritize individual choice and supposed market-based solutions. For example, he has targeted the Centers for Disease Control and Prevention (CDC), arguing that its focus should be limited strictly to communicable diseases, labeling other areas of its work as "mission creep." Blase also seeks to roll back expanded pandemic-era subsidies for insurance coverage under the Affordable Care Act, suggesting that these subsidies should be allowed to expire after 2025. I would expect nothing different from an administration which tried repeatedly (and failed) to repeal President Obama's signature piece of legislation. Instead, he promotes Health Savings Accounts (HSAs) as a preferred mechanism for individuals to manage their healthcare costs.

However, the reality for many Americans, particularly lower-income individuals, is that HSAs are simply not even a viable option. As TurboTax data reveals (see https://turbotax.intuit.com/tax-tips/tax-deductions-and-credits/tax-deduction-wisdom-should-you-itemize/L8Ln7K0Gp?form=MG0AV3 for more), 90% of taxpayers choose the "standard deduction" rather than itemizing their deductions, highlighting the limited tax benefits for most individuals. For someone earning minimum wage, the standard deduction significantly exceeds their potential itemized medical expenses, rendering HSAs largely ineffective and moot to that segment of the population.

Bai, acknowledging Paragon's growing influence in her November 2024 NPR interview ("All Things Considered"), commented:

"I was, like, there's no way this institute will make any splash. But now, after three years, I think they've become such a prominent figure."

She also noted Paragon's influence on congressional members and staffers, although she later clarified that this primarily Republican members, and it should also be noted that her assessment regarding staff influence was largely speculative on her part.

While Bai may have initially underestimated Paragon's impact (she herself is politically conservative), its rise within the Trump administration cannot be ignored. This raises concerns about the potential for a shift in healthcare policy towards a more market-driven, less-regulated approach. But when it comes to pharmaceuticals, that argument falls apart because there is nothing "free" about that industry or that market. Drug companies are selling government-granted monopolies which are highly regulated, and only the distribution system is largely unregulated, and due to a lack of oversight of that, we now have middlemen in the system gaming the system for their own financial benefit at the expense of patients and employer healthcare plan sponsors alike. But the Trump administration has demonstrated a willingness to challenge at least one status quo in healthcare, as evidenced by his failed 2020 executive order ("EO") aimed at addressing PBM rebate kickbacks. 

Trump's Previous Executive Order on PBM Kickbacks Never Went Into Effect

It was absolutely true that on November 20, 2020 (after losing the 2020 election), the outgoing Trump administration issued an Executive Order ("EO") to finally address (which had conveniently been ignored for 4 years) the PBM rebate kickback problem, and I was optimistic that could potentially deliver on a campaign promise to help reduce prescription drug prices for Americans. 

Alas, in typical Trump fashion, the outgoing Trump administration had failed to provide 60-days' notice soliciting public comments on the proposed policy-change which was a clear violation of federal law, which meant that the incoming Biden administration faced an immediate lawsuit over the Trump Executive Order ("EO"). 

To avoid further litigation over process, the incoming Biden administration's Dept. of HHS simply "froze" implementation of the Trump EO for 60 days in order to comply with the law that requires public input on policy changes. But then, the PBM trade association known as the Pharmaceutical Care Management Association (PCMA) sued the U.S. Dept. of Health and Human Services over the Trump EO, and a federal judge ordered that the Trump EO must be frozen until the PCMA litigation was addressed in Court (either in a court ruling, or a settlement). The outcome of that lawsuit was still pending as it as I wrote this (the courts aren't speedy).

The previous Trump administration had also considered some other options such as banning "Most Favored Nation" pharmacy/PBM contracts and promoting "cost plus" drug spending, which could significantly impact the pharmaceutical industry and patient access to medications, only he was no longer President at the time, hence he no longer had power to do those things. However, the unpredictability of the previous Trump administration, coupled with the ongoing legal battles surrounding his 2020 EO, makes it difficult to predict any long-term consequences of these policy shifts.

One thing is certain:

The debate over PBMs, runaway healthcare costs, and the role of government intervention is far from over. The coming years will likely witness continued clashes between powerful business interests for commercial healthcare insurance company-owned PBMs and a growing chorus of voices (including from employer healthcare plan sponsors) demanding a more equitable and affordable healthcare system for more covered Americans. Given Trump's prior failures, that means that we'll basically have to watch how he executes his EOs going forward. He failed the first time, but maybe this time he'll follow the law in executing them this time around? 

Navitus 2023 Drug Trend Report

You may recall that in July 2023, I shared news (see my post at https://blog.sstrumello.com/2023/07/navitus-2022-drug-trend-report.html for that) of a PBM 2022 "Drug Trend Report" which is still being published, specifically from the PBM known as Navitus Health Solutions. In recent years, Drug Trend Reports have been discontinued by many of the biggest PBMs (CVS Caremark, Cigna Express Scripts and United Healthcare OptumRx), but at least one of the smaller PBMs has still continued with the tradition. 

Navitus is one of the smaller PBMs, and its ownership structure is unique. In my prior coverage of (see HERE), and in my coverage of the release of the 2022 Navitus Drug Trend Report, I noted how Navitus is jointly owned by SSM Health, a not-for-profit health system [which has 65% ownership stake in Navitus] based in the midwest, and the retailer Costco Wholesale [which has a 35% ownership stake in Navitus]. For its part, Costco Wholesale has leveraged its co-ownership of a PBM to ensure that it, as a retailer, can avoid many of the unscrupulous PBM business practices which have driven other big retailers such as Target out of the pharmacy business completely. 

In essence, Navitus goes through every contract on behalf of Costco Pharmacy from bigger PBMs including CVS Caremark, Express Scripts and OptumRx in order to help to avoid bad contract language which might enable those PBMs to take advantage of a pharmacy retailer such as Costco Pharmacy. It can't completely avoid the games PBMs play, but having Navitus review each PBM contract enables Costco to avoid some of the most egregious contract terms.

Anyway, in 2024, Navitus published a newer version of its Drug Trend Report (see the Navitus press release at https://info.navitus.com/dtr-2023-snapshot and the executive summary of the 2023 Drug Trend Report itself at https://4437620.fs1.hubspotusercontent-na1.net/hubfs/4437620/2023%20Navitus%20Drug%20Trend%20Report%20Executive%20Summary.pdf to download a copy of its 2023 Drug Trend Report executive summary). 

To be sure, the Navitus 2023 Drug Trend Report has grown ever-smaller from previous years reports. But unlike its bigger rivals CVS Caremark, Express Scripts, and OptumRx, at least Navitus still made an effort to publish one, even if it's not very detailed as those reports once were.

On page 2 of the 2023 Navitus Drug Trend Report executive summary, you will observe something interesting: It says: 

"Significant Trend Driver: Glucagon-like peptide 1s (GLP-1s)". 

Of course, that failed to acknowledge how Costco itself had originally helped to drive that trend with its collaboration with Sesame Care, a telehealth provider who prescribes the newest, most expensive GLP-1s to anyone who asks for them (catch my coverage of that HERE for more, although it is no longer about pushing overpriced Novo Nordisk GLP-1s exclusively). 

The Navitus 2023 Drug Trend Report executive summary also adds:

"Due to varying coverage decisions by clients, GLP-1s for weight loss were not included in the Drug Trend Report, yet they still warrant thoughtful consideration and conversation in the overall picture of trend and future decisions."

It continued: 

"GLP-1s [for Type 2 diabetes] are also costly. Diabetic GLP-1 medications were the biggest contributor to trend growth in 2023, where this single class of medication increased the overall trend by 1.7%, even though less than 3% of our members used the medications."

 

Navitus said: "...to help clients control use to approved [Type 2] diabetes indication, Navitus implemented a pharmacy point-of-service diagnosis check. Those clients who implemented the point-of-sale utilization management control mitigated 30% of prescription fills by preventing those without an appropriate diagnosis." 

Aren't PBMs Supposed to Do That Automatically? Why's a Client Opt-In Required?

That sounds pretty much as if Navitus is verifying that a patient attempting to fill a prescription for a costly GLP-1 product such as Ozempic must properly coded to have a clinical diagnosis of Type 2 diabetes, or the prescription cannot be filled. This prevents off-label prescribing of T2D drugs for weight-loss. It's unclear how extensive that matter actually is. It could be an issue, but this type of diagnosis code cross-check is what PBMs claim they do on an automated basis. Hence, I question the necessity for clients "who implemented the point-of-sale utilization management control". Aren't PBMs supposed to be doing this automatically? Why must their clients "opt-in" for that?

Ryan Schmidt, Associate Director, Client Financial Support of Navitus, said in an interview (see https://www.navitus.com/in-the-news/increased-glp-1-drug-use-adds-to-navitus-2023-drug for her comments) citing data from the firm IQVIA which predicted that spending on the GLP-1 class of therapeutics was expected to grow by 378% to $8.1 billion by 2027, but Ms. Schmidt would only say that "there will likely be increased discussions about how to cover the GLP-1 therapies, especially in light of the added benefit they may have for some patients".

For the record, although Navitus laments the price tag of the newest branded GLP-1s for Type 2 diabetes, it also adds that Navitus Health Solutions doesn't have a single "preferred" GLP-1 brand. Instead, Navitus says it covers several different GLP-1 medications, including both the newer brand-name options like Ozempic (semaglutide) and Mounjaro (tirzepatide), as well as generic alternatives (such as liraglutide). Navitus said that its approach focused on providing cost-effective options, including generics and biosimilars, to ensure members have access to necessary medicines. In 2024, two generic/biosimilar versions of liraglutide hit the market (catch my most recent coverage of that HERE for more).

Under the heading of Medical Device, Navitus observes:

"The medical device category includes products such as continuous glucose monitors (CGMs) and wearable insulin pumps for patients with diabetes. CGMs are costly and may exceed $1000 per month. Usage of these devices grew by 50% in 2023, which contributed to increased spend in the category by 40% over the previous year."

To my knowledge, Navitus does not appear to collect "legally-exempted rebate kickbacks" for the purpose of "formulary exclusion" of non-preferred CGM brands as United Healthcare's OptumRx or Aetna/CVS Caremark currently do. At least that part is rational. Still, because Dexcom pays PBMs "legally-exempted rebate kickbacks" to prefer Dexcom CGM sensors, rather than Abbott Libre sensors (whose 14 or 15 day wear-times compared to Dexcom's 10 day wear-time means Libre is about 40% less expensive than Dexcom is).

I reached out to Ryan Schmidt who works for Navitus at its headquarters in Madison, Wisconsin. Her title is not only Registered Pharmacist (RPh) but also Associate Director of Business Insights for the PBM. Her title is not only Registered Pharmacist (RPh) but also Associate Director of Business Insights for the PBM. I was curious to speak to her about things already available which have potential to bend the upward cost curve on GLP-1s such as generic versions of liraglutide (fka Victoza/Saxenda), and also if telemedicine ever comes up in the dialogue Navitus has with clients/prospects about the cost of GLP-1s, or if perhaps Navitus believes that maybe telemedicine really SHOULD come up since it is a known contributor to the prescription volume for the overpriced medicines? 

We know thanks to STAT News reporting that a small number of doctors, nurse practitioners, and physician assistants write almost ALL of the thousands of prescriptions for the numerous websites offering weight-loss drugs (see https://www.statnews.com/2024/10/17/telehealth-online-compounded-glp1-prescriptions-medical-groups/), and those telemedicine providers typically prescribe only the newest, most expensive GLP-1 inhibitors (generic companies don't pay for telemedicine providers, branded companies do), and in fact, those prescribers often try to dissuade patients who might inquire about generic alternatives from even considering those in spite of those being considerably less expensive.

I reached out to Ryan Schmidt to ask if she would comment on the Navitus "opt-in" requirement to ensure drugs for Type 2 diabetes are not improperly being prescribed without a diagnosis code of Type 2 diabetes might be used improperly for weight-loss without Type 2 diabetes, and also seeking answers to my questions about whether Navitus discusses any of the recently approved generic GLP-1s now available or whether they should be "preferenced" over more-costly newer GLP-1 products, but so far, I have not yet received a response from her or anyone else at Navitus, but I'd love to hear how the PBM responds.

Why I Pushed for the FTC Litigation Against the PBMs, While Diabetes Advocacy Orgs Did Not

As some of you who still follow me may realize, back in 2021, I set out to make sure the proper government agency addressed the wrongdoing occurring in the U.S. insulin market. The reason Americans were paying insane prices for insulin (10 mL vials of widely-prescribed insulin varieties were being sold for more than $200 in the U.S., compared to about $37 to $48 in virtually every other country on earth) and that was because Americans were being forced to pay for bribes/kickbacks. Admittedly, they were "legally-exempted" kickbacks, but we were paying for bribes nevertheless, which was not only wrong (and patients were suffering for it), but quite likely illegal.

I set my sights upon the U.S. Federal Trade Commission (FTC). I had not initially considered FTC before, but it occurred to me that FTC was the only government agency which has the power to do it. This was the entity which broke-up AT&T (the old "Ma Bell") in 1984, where my father was employed for my entire childhood. 

Broadly speaking, the role of the FTC is to enforce federal consumer protection laws that prevent fraud, deception and unfair business practices. A new administration might try to change that role but that's the reason FTC exists (and by law, commissioners must be from both major political parties). The Commission also enforces federal antitrust laws that prohibit anticompetitive mergers and other questionable business practices that could lead to higher prices, fewer choices, or less innovation. Again, a new administration may attempt to re-write that reality, but that's the role which Congress established for the FTC when the FTC Act was passed into law back in 1914. 

Some of my move was due to a timing issue. 

I aimed to leverage laws which were already on the books to seek relief. You don't need to thank me; I acted as much in self-interest as in philanthropy. With a "conservative" in the White House and a Congress either unwilling and/or unable to address the issue, I planned to jump upon the issue as soon as President Biden was inaugurated in 2020. While anticompetitive issues should theoretically be important to conservative lawmakers as well, the practical reality was that big, monopolistic interests have bankrolled conservative political candidates who have vowed for the FTC to take a completely "hands-off" approach to unfair competition and monopolies. So, I acted when the political wind was at my back.

Ideally, diabetes nonprofit organizations should really have pushed for the same, but instead, the big ones (the American Diabetes Association [ADA] and Breakthrough T1D/JDRF) had not really taken much interest, even while they knew very well what was happening (bribery). 

Instead, the organizations like the ADA adopted a largely ineffective grassroots "Make Insulin Affordable" initiative (it was not even a campaign; see the press release at https://www.prnewswire.com/news-releases/american-diabetes-association-reaffirms-commitment-to-insulin-access-and-affordability-for-all--transparency-on-insulin-pricing-critical-300752216.html for more), but the initiative was mostly toothless, and nothing really happened. 

To its credit, I must acknowledge that Breakthrough T1D/JDRF did something which was strategically very effective, even if it took several years for patients to realize the benefit of what it did. 

Recall that on March 3, 2022, Breakthrough T1D (then known as JDRF) announced https://www.prnewswire.com/news-releases/jdrf-announces-support-of-civica-to-manufacture-and-distribute-low-cost-insulin-301495050.html (with specific details about intended pricing) along with nonprofit drug company partner Civica, Inc. (see Civica's concurrent press release at https://www.businesswire.com/news/home/20220303005321/en/Civica-to-Manufacture-and-Distribute-Affordable-Insulin/ for more, including the reveal that it was collaborating with an India-based company known as GeneSys Biologics to actually make the insulin API [the acronym for Active Pharmaceutical Ingredient] inexpensively enough to sell at those prices, and to effectively compete with Lilly, Novo Nordisk and Sanofi) announced that Civica intended to introduce biosimilar versions of insulin glargine, insulin aspart and insulin lispro (better known by the trade names of Sanofi Lantus, Novo Nordisk Novolog and Lilly Humalog), which would be sold at a price of no more than $30/vial and $55/box of five prefilled disposable insulin pens, regardless of insurance status. Those biosimilar insulins are pending FDA approval decisions as I write this. But the intended effect has already happened. 

The Civica biosimilar insulin announcement was indeed very disruptive to the underlying pharmaceutical business, because it essentially established a cash price ceiling for most insulins sold in the U.S. Previously, insulin manufacturers had primarily used the rebate-contracting sales model promoted by the big Pharmacy Benefit Managers (PBMs) to sell insulin, with massive discounts given in the form of multi-million dollar cash-rebates (I refer to those rebates as "legally-exempted rebate kickbacks" because that is what they are, and if you describe them that way, no one including Federal lawmakers can misunderstand what they are) which may be (but very frequently were not) passed along to the covered patients. 

That Civica insulin move meant that every other biosimilar copy of insulins would be unable to sell their products for any more than $30/vial and $55/box of five prefilled disposable insulin pens. It also put incredible pressure upon Lilly, Novo Nordisk and Sanofi to effectively match those prices. The major insulin manufacturers had previously made moves to sell "unbranded" versions (these insulins are sold under the generic drug name, rather than the brand-name) of several (but not all) of their better-selling insulin analogues. That was done to avoid pissing-off the big insurance company affiliated PBMs.

The unbranded insulin (unbranded insulins are not actually generics or biosimilars because they are made by the innovator companies) initiative began in 2019 when Eli Lilly & Company, Inc. was the first to announce it would introduce a cheaper "unbranded" (sold under the generic drug name) version of Humalog (see https://www.prnewswire.com/news-releases/lilly-to-introduce-lower-priced-insulin-300805560.html for the press release). Rival Novo Nordisk copied the move very soon after (see https://www.prnewswire.com/news-releases/novo-nordisk-launching-additional-us-insulin-affordability-offerings-in-january-2020-300913167.html), although Sanofi did not do so until nearly two years later (see https://www.news.sanofi.us/2022-06-29-Sanofi-to-lower-out-of-pocket-cost-of-insulin-for-uninsured-patients-and-expand-access-in-underserved-communities for its announcement). Those were efforts by pharma to try and circumvent the noncompetitive lock on U.S. insulin prices which PBMs had on the market, and they did work...well, sort of. 

Those unbranded insulin introductions were intended to help patients with access to products which were affordable, as long as patients knew where to look, and unfortunately, many did not, nor did pharma invest a penny to promote their existence. While the list price was about half of branded Humalog, savvier patients like me quickly discovered I could buy Lilly Insulin Lispro injection for about 75% less simply by also using a GoodRx coupon. That also happened with Novo Nordisk's unbranded insulins (which Novo Nordisk Pharma Inc.'s happened to recently announce that the company would be discontinuing all unbranded biologic versions of insulins sold in the U.S. by December 31, 2025 because its branded insulin price-cuts in the U.S. will fully be in effect by that date). Ditto for the unbranded Insulin Glargine Injection from Winthrop by Sanofi. 

But a year after Lilly introduced the "unbranded" version of Humalog, during a quarterly earnings call with investors, someone asked management for more info on what portion of sales were branded vs. unbranded, and surprisingly, Lilly management revealed that nearly one-third of domestic Humalog sales were the unbranded version of Humalog. Investors were kind of stunned, but that led Lilly to disclose the branded/unbranded sales in subsequent earnings releases.

But it was really not until the insulin manufacturers themselves subsequently introduced their own manufacturer coupons (Lilly's coupons were/are offered at https://www.insulinaffordability.com/, Novo Nordisk's were/are offered at https://www.novocare.com/diabetes/help-with-costs/savings-offers.html, and Sanofi's were/are available at https://www.teamingupfordiabetes.com/sanofidiabetes-savings-program), which effectively made their unbranded insulin varieties at a cost of $35/vial or $55/box of 5 insulin pens, and those prices had become a de facto standard available to U.S. patients...again, provided they knew WHERE to look for them. So, I spent considerable energy to ensure people knew about them. Incidentally, today, we also have similar coupons on CGM sensors. And also on 'modern' glucagon rescue products. If you read the web page version (not on a mobile device) of this blog, you will find them all listed in the right-hand margin.

The American Rescue Plan of 2021 (see https://progressivepolicyinstitute.medium.com/are-we-on-the-cusp-of-a-new-drug-pricing-paradigm-fdf611c009b3 for details on how that worked) also played an important role, because that law eliminated a cap on drug rebates which were payable to MedicAID, starting on Jan. 1, 2024. In essence, the American Rescue Plan of 2021 eliminated a "cap" on rebates which were payable to Medicaid, meaning companies which sell older, but heavily-rebated (to PBMs) medicines such as insulin were faced with the prospect that they might actually be forced to PAY Medicaid for their rebated-drugs if their "rebate" marketing expense caused drug prices to rise faster than inflation, and there was no way pharma would ever do that. So, they slashed prices to avoid that predicament. That incentivized Lilly, Novo Nordisk and Sanofi (and to a slightly lesser extent, Biocon) to slash their insulin list prices in order to avoid negative pricing consequences.

So on March 1, 2023, in recognition of everything that was happening, Eli Lilly & Company, Inc. https://www.prnewswire.com/news-releases/lilly-cuts-insulin-prices-by-70-and-caps-patient-insulin-out-of-pocket-costs-at-35-per-month-301758946.html made the first move to slash insulin prices, then on March 14, 2023 Novo Nordisk, Inc. https://www.prnewswire.com/news-releases/novo-nordisk-to-lower-us-prices-of-several-pre-filled-insulin-pens-and-vials-up-to-75-for-people-living-with-diabetes-in-january-2024-301771409.html did the same, then on March 16, 2024 Sanofi-Aventis U.S. LLC (and its subsidiaries) https://www.globenewswire.com/en/news-release/2023/03/16/2629188/0/en/Press-Release-Sanofi-cuts-U-S-list-price-of-Lantus-its-most-prescribed-insulin-by-78-and-caps-out-of-pocket-Lantus-costs-at-35-for-all-patients-with-commercial-insurance.html all announced major list price cuts for their (but patent-expired) branded and unbranded insulins (duplicates sold under the generic drug name in an effort to bypass PBM-driven price markups). In order to pay for those deep price-cuts, the major branded insulin manufacturers would simply disintermediate the PBM's from the transactions (they would no longer pay PBM kickbacks). In other words, they would slash prices on patent-expired insulins, and to pay for the massive price-markdowns, they simply cut the PBM's out of the transaction by no longer paying them legally-exempted rebate kickbacks on insulins.

The FDA also played a small role to enable the biosimilar rush to happen. Specifically, the Affordable Care Act provision known as Biologics Price Competition and Innovation Act (BPCI Act) which went into effect in 2010 (see https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-actions-advancing-agencys-biosimilars-policy AND https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-continued-efforts-bring-competition-insulin for more) formally implemented a much-needed policy change. But the FDA waited for a decade before it acted, whereby it transitioned certain biological products originally approved as "drugs" under the Federal Food, Drug, and Cosmetics Act (FD&C) to be formally licensed as "biologics" under the Public Health Service Act (PHS), making them subject to biosimilar competition for the first time. That enabled many biosimilar versions of bestselling insulins to have a viable approval pathway to market with the FDA, while it also enabled less costly biosimilar competition to come to market for the first time. 

Right now, biosimilar insulins from Civica (via the company's CivicaScript operating unit which has a unique Retail Unilateral Pricing Policy [UPP] on all drugs it sells), as well as from Sandoz, and also a number of copies of some (but not all) insulin analogues from such companies as Biocon, Lannett Company and Amphastar Pharmaceuticals all expect FDA approval decisions at any time, most likely starting in the first quarter of 2025. In addition, copies of all of the three bestselling insulins are also now in development from Chicago-based Meitheal Pharmaceuticals as well. 

That new reality essentially forced Lilly, Novo Nordisk and Sanofi to simply abandon the rebate-contracting sales model for insulins. Of course, Novo Nordisk (in particular) is still paying PBMs massive rebate kickbacks in order to keep all competing GLP-1 inhibitor drugs (including generics) "off-formulary" (it's almost as if Novo Nordisk's U.S. unit learned absolutely nothing from what happened on insulin sold in the U.S.).

But who was working to ensure that the horrendous wrongdoing from PBMs no longer happened? 

The answer is no one was. 

Really, the FTC issue should ideally have been advanced by Breakthrough T1D's Chief Global Advocacy Officer Lynn Starr, but why that never came up remains a complete mystery to me. I did not bother waiting for that organization (or any other) to do it. Instead, I took it upon myself. So I stepped in, and I allied myself with various like-minded independent pharmacy organizations including the National Community Pharmacists Association (NPCA) to really push the FTC to investigate corporate wrongdoing at the biggest PBMs, not one single government entity or nonprofit organization was working on the illegal (or legally questionable) PBM activity. 

I worked to make that happen (and luckily, I was in a position to make it happen). It began when FTC held "open meetings" in 2020, and in every one of those meetings, someone spoke and mentioned PBM wrongdoing. It seemed very clear that an investigation of the PBM behaviors was in order. My motive was to end this criminal behavior, at least related to the sale of insulin.

On June 6, 2022, the FTC voted unanimously on a bipartisan basis (including both Trump-named FTC commissioners) to initiate a comprehensive 6(b) study of the Pharmacy Benefit Manager (PBM) Industry business practices (see the news release at https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-launches-inquiry-prescription-drug-middlemen-industry for more details). The FTC referred to that study as "FTC Matter No. P221200" and FTC released its first Interim Report" https://www.ftc.gov/news-events/news/press-releases/2024/07/ftc-releases-interim-staff-report-prescription-drug-middlemen from that study on July 9, 2024. 

On September 20, 2024, the FTC filed a legal "complaint" (a lawsuit; see https://www.ftc.gov/news-events/news/press-releases/2024/09/ftc-sues-prescription-drug-middlemen-artificially-inflating-insulin-drug-prices for more) in Administrative Court alleging that CVS Health's Caremark Pharmacy Benefit Manager ("PBM") business, rival Cigna's Evernorth/Express Scripts PBM and another rival UnitedHealth's Optum Rx PBM business had all collectively accepted money in the form of multimillion dollar cash "rebate" kickbacks from drugmakers in exchange for keeping lower-cost insulin varieties off their preferred drug formularies (lists of approved drugs). See https://www.ftc.gov/news-events/news/press-releases/2024/09/ftc-sues-prescription-drug-middlemen-artificially-inflating-insulin-drug-prices for the court filing. The lawsuit also named their respective affiliated "Group Purchasing Organizations" [GPOs] — started in recent years to negotiate cash rebate payments with drugmakers — known as Zinc Health Services, Ascent Health Services, and Emisar Pharma Services respectively, which they now use primarily for "rebate aggregation". 

The FTC's Notice of Contemplated Relief is as follows:

1. Prohibit Respondents [the PBMs] from excluding or disadvantaging low Wholesale Acquisition Cost (WAC) versions of high WAC drugs made by the same manufacturers whenever the Respondent covers the high WAC drug on a formulary. In other words, the PBMs would not be permitted to exclude lower-priced versions of insulins such as Lilly's "unbranded" (sold under the generic drug name) insulin called Lilly Insulin Lispro Injection if they put branded Humalog on-formulary. Ditto for any "unbranded" insulins from Novo Nordisk, Winthrop by Sanofi, or Biocon.
   
   
2. Prohibit Respondents [the PBMs] from accepting compensation based on a drug's list price or a related benchmark.
   
   
3. Prohibit Respondents [the PBMs] from designing—or assisting with designing—a benefit plan that bases patients' deductibles or coinsurance on the list price, rather than the lower realized "net" cost after rebates.
   
   
4. Order any other relief appropriate to correct or remedy the Respondents' [the PBMs] violations. This would be using the Courts to ensure these relief efforts to happen.

The FTC press release on its litigation can be viewed at https://www.ftc.gov/legal-library/browse/cases-proceedings/221-0114-caremark-rx-zinc-health-services-et-al-matter-insulin but naturally, the PBM trade organization known as the Pharmaceutical Care Management Association (PCMA) and the individual PBMs countersued the FTC over its legal existence and for "defamation" among other things. 

However, the law firm known as Frier Levitt published an update on the status as of December 4, 2024 (see https://www.frierlevitt.com/articles/update-on-ftcs-lawsuit-against-three-largest-pbms-and-their-gpos/ for its write-up). Lawyers suggest the PBM countersuits are likely a possible delay tactic, as well as a message to the FTC that they will litigate to preserve their not-so-little kickback scheme for as long as possible.  But the consensus is the PBMs' odds of success are quite poor. This is now essentially a done deal. Bigger companies have tried and failed to fight the FTC. Among them include Standard Oil in 1911 and AT&T in the 1984, but they failed, and the PBMs will likely fail, too. 

I did this because the PBM behavior was (at best) on legally questionable ground, or more likely, was overtly criminal and anticompetitive behavior, and more importantly, it was screwing patients and employer healthcare plan sponsors alike out of money we were really entitled to. The laws were on the books for decades, and yet no one was enforcing those laws, so citizens like me helped make it happen. I only wish that some big diabetes advocacy organizations were willing to help me out, but they did not, so we patients were forced to do it on our own.

Again, you are welcome... 

Author P.S., January 14, 2025: As a second part of the FTC's 6(b) study (FTC Matter No. P221200), the Federal Trade Commission released a Second Interim Report on that study entitled "Specialty Generic Drugs: A Growing Profit Center for Vertically Integrated Pharmacy Benefit Managers" (see the press release HERE, and the report itself HERE) in which the largest PBMs were charged with unlawfully declaring many generic drugs as "Specialty Medications" in order to force covered patients to acquire those medicines only from "Specialty Pharmacies" owned and operated by the PBMs themselves, and the PBMs then marked the prices-up on what should have been inexpensive generic drugs by thousands of percents. Separately, the FTC moved to have CVS Health's General Counsel attorney Sam Khichi disbarred as a lawyer (meaning he would not be able to practice law again) for repeated failure to respond to lawfully-issued subpoenas and effectively just ignoring them as if the company had never received them. Evidently, the FTC has the legal authority to have law licenses revoked if repeated wrongdoing occurs.

Ask the FDA: Why Aren't the Insulin Biosimilars Coming? What the Hell is the Hold-Up?

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."

Assuming Lannett Company's management did not experience any unforeseen delays, then I think we can presume that sometime in early 2023, it had submitted its application for glargine's approval. On Wednesday, September 9, 2022, the periodical known as Drug Store News released a brief story which pretty much said it all in the story headline: "Lannett anticipates launching biosimilar insulin glargine in the first half of 2024" (see https://drugstorenews.com/lannett-completes-clinical-trial-subject-dosing-biosimilar-insulin-glargine for the article). Obviously, that did not happen in the first half of 2024, nor has FDA released any statements indicating it has rendered any approval decisions thus far. But if we assume a three-year turnaround time, then I think we can assume that if an application was submitted in Q1 2023, that would mean that sometime in Q1 2025 (between January and March 2025) we should have some announcement from FDA regarding Lannett's copy of insulin glargine.

This assumes Biocon's FDA approval timeframe for Semglee will be the same for other applicants. Lannett Company's insulin glargine biosimilar is currently still "under consideration" by the U.S. Food and Drug Administration right now. And so are those from Sandoz/Gan & Lee, as well as Civica/GeneSys Biologics, Amphastar Pharmaceuticals/ANP and several others. In my view, it looks like there is a backlog, and my question is when will we start receiving some actual FDA decisions?

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?!