Author: Morgan Doyle

Overcompensation?: The FDA Nixes Boxed Warnings for MHT Drugs

The U.S. Food and Drug Administration (FDA) recently removed boxed warnings for six menopausal hormone therapy treatments (MHTs), drugs that reduce the uncomfortable side effects of reduced estrogen levels. These are the FDA’s highest level of warnings that appear on drug packaging in bold print and warn users of serious adverse reactions or important dosing restrictions. For MHT, the boxed warning informs consumers that MHT increases the risk of cardiovascular disease, breast cancer, and dementia.

Although this may look at first glance like another one of the current administration’s attempts to flip food and drug law on its head, a closer look at the scientific findings that prompted the boxed warning indicates it’s not so simple. Originally, the FDA mandated boxed warnings for MHT drugs after the Women’s Health Initiative (WHI) conducted a study in 2002, finding coronary heart disease and invasive breast cancer as primary adverse outcomes based on largely observational data. After the warning was implemented, usage dropped 22% for menopausal women from 1999 to 2020.

However, the safety and long-term risks of MHT have been debated by scientists, particularly because of the WHI study’s controversial design. The study had two main design flaws: it included women with an average age of 63, and the study tested synthetic hormones that are not the same as MHT drugs on the market today. The average age of participants was problematic because women generally experience menopause around age 51.5, but women around 63 years old are more likely to have preexisting cardiovascular issues. Furthermore, the use of synthetic hormones in this study means the adverse health outcomes are not necessarily attributable to the MHT treatments currently on the market. Additionally, modern MHT treatments use lower doses of estrogen and can be delivered through the skin may further reduce the likelihood of adverse events.

FDA panelists were urging the removal of boxed warnings specifically for vaginal estrogen because it poses the lowest risk of adverse effects. When this route of MHT treatment is taken, less estrogen is absorbed in the patient’s bloodstream, which lowers the risk of blood clots, stroke, and cancer. However, the FDA ultimately chose to remove boxed warnings for all estrogen-containing MHT treatments.

Under the Federal Food, Drug and Cosmetic Act, drug labeling must reflect current and accurate science-based evidence without misleading consumers. There is a risk that removing these warnings about increased risks of cardiovascular disease, breast cancer, and dementia for all estrogen-containing MHT treatments was premature, despite the shortcomings of the WHI study. If labels understate risks of MHT treatment, companies may risk facing claims of misbranding drugs under the Act, even though the FDA no longer requires the boxed warning for six current MHT drugs.

Women deserve a better solution than an outdated, poorly designed study for MHT drugs. Instead of risking liability or debating whether the WHI study is accurate enough to make the FDA require boxed warnings about serious adverse effects, the government should provide a grant for a new study on MHT drugs in menopausal women with a younger average age than the previous study.

The Patent Thicket Just Got Thicker: Limiting Inter Partes Review for Biologic Drug Patents

While a best-selling small molecule drug could be covered by up to five patents, biologic drugs (large chemical compounds produced by living cells) are covered by hundreds of patents. A primary purpose of patents is to give a limited monopoly to inventors to incentivize innovation, but this monopoly comes at a cost to consumers. For example, Humira (a rheumatoid arthritis medication) has 134 active patents and AbbVie Inc. charges consumers $6,500 per month for treatment. Most of these patents are “secondary patents” of questionable validity, covering things like dosage, drug formulations, and methods of using the drug to treat a new condition.

To combat these exorbitant prices, companies have been using biologic drugs as templates to produce biosimilars—therapeutically equivalent molecules. Without the extensive research and development costs associated with producing a novel biologic drug, biosimilars are brought to market and sold for less—around 90% less. Returning to the previous example, the biosimilar for Humira cost as little as $650 per month—just a tenth of the $6,500 monthly payment for the brand-name biologic.

The price of biosimilars could become even more affordable due to a recent announcement from the U.S. Food and Drug Administration (FDA) that it would be simplifying the process by which companies could bring biosimilar drugs to market. Now, the FDA will allow biosimilar manufacturers to circumvent expensive clinical testing in exchange for analytical testing. The manufacturer must show that their biosimilar does not have any clinically meaningful differences from the brand-name biologic drug (which has undergone clinical testing). The FDA used to require biosimilars to conduct “switching” clinical tests where patients would be treated first with the biosimilar drug then with the biologic drug (or vice versa) to determine any difference in responses to the drugs. If no meaningful differences were found, then the biosimilar was given “interchangeable” status, allowing pharmacists to prescribe the cheaper biosimilar instead of the brand-name biologic.

However, generic drug companies face another issue: challenging the validity of patents on a brand-name biologic drug. The web of patents protecting a single biologic drug makes it difficult for generic drug companies to enter the market because they must first demonstrate all the existing patents are invalid or not infringed by their product. Litigating these patents in a district court is expensive, complicated, and time-consuming.

Inter partes review (IPR) exists as an easier way for generic drug companies to clear out the patent thicket created by brand-name biologic drug manufacturers. However, the U.S. Patent and Trademark Office (USPTO) proposed a rule shortly before the FDA’s announcement, limiting the ability of biosimilar manufacturers to challenge the numerous patents filed on brand-name biologics. Previously, biosimilar manufacturers often used IPR through the Patent Trial and Appeal Board to challenge the validity of patents on brand-name biologic drugs. Now, IPR will not be available when “a petitioner intends to pursue invalidity challenges under §§ 102 [novelty requirements] or 103 [non-obviousness requirements] in other venues, such as district court or the U.S. International Trade Commission.” The USPTO frames this amendment as a way to “promote fairness and efficiency by channeling similar patent challenges to a single forum” and ensuring that IPRs are, not used in addition to, but as a complete substitute for, at least a phase of litigation. This has the effect of eliminating IPR as an avenue for biosimilar drugs to challenge the validity of broadly-drafted patents restricting their entry to the market, and thus increasing the cost of determining whether the numerous brand-name biologic drug patents are valid.

Allowing biosimilar manufacturers to use IPR as an avenue for challenging brand-name patent validity is important for two main reasons: lower costs and accelerated market entry. First, only 5% of prescription drugs are biologic drugs, but they account for $300 billion dollars in national total spending on medications. Thus, by creating therapeutic equivalents to patented biologics—biosimilars—which can compete with brand-name biologic drugs, prices will drop closer to the marginal cost of production and become more affordable to regular Americans. Second, legal battles between biologic manufacturers and brand-name biologics manufacturers can last years, delaying the arrival of affordable alternatives to consumers. Returning again to Humira as an example, it took seven years in court before the patent issues were resolved and the biosimilar could reach the market.

Although patents are meant to incentivize innovation by providing a limited monopoly, they are also meant to increase public access to cutting edge, socially beneficial technology, such as biologic and biosimilar drugs. By making it more difficult for biosimilar manufacturers to challenge validity of biologic drug patents, inventors and their monopoly are protected, but the USPTO has forgotten the public which patent law also seeks to protect.

A Brief Respite from a Barrage of Anti-Trans Executive Orders

On February 14, 2025, a second federal judge halted President Trump’s executive order banning federal support for gender-affirming care for transgender youth under 19. The “denial-of-care” executive order came after a barrage of other orders discriminating against trans and nonbinary Americans in areas like the military, sports, and federal prisons. President Trump’s denial-of-care executive order would cut off federal funding for institutions, such as hospitals, providing gender-affirming care like hormone treatments and puberty blockers for trans and nonbinary youth. The executive order would also force federally funded insurance programs like Medicaid to stop providing coverage for gender-affirming medical care for youth. 

The attorney generals of Washington State, Oregon, and Minnesota sued the Trump administration on the grounds of equal protection and spending power violations. Judge Lauren King from the Western District of Washington granted a temporary restraining order on the executive order for 14 days, which came as a relief to many Americans. The decision came a day after a Baltimore federal judge blocked the same executive order in a case filed by families with transgender or nonbinary children. On February 19, 2025, Colorado joined the three other states in the suit against the Trump Administration.

In their amended complaint, the attorney generals assert that President Trump’s executive order violates Constitutional principles on multiple grounds. First, it denies equal protection to transgender and nonbinary people by discriminating against a vulnerable minority group without a legitimate government interest. Second, it usurps congressional legislative and exclusive spending powers. Third, it violates the Tenth Amendment separation of powers doctrine by attempting to unilaterally, and without congressional approval, interfere with the medical profession which is traditionally within States’ police powers.

The Trump administration claims that it has a legitimate interest in protecting children from treatments with negative health consequences, but this rings false. The Trump administration’s true interest is fueling their disinformation campaign characterizing transgender as an “ideology” that must be stopped from taking hold. This characterization paired with far-right social media accounts has led to threats and violence against gender-affirming care providers. For example, the Boston Children’s Hospital received 3 bomb threats and continued online harassment after right-wing social media users made misleading claims that the hospital was performing hysterectomies on children and “needed to be stopped.”

Furthermore, the denial-of-care executive order has had drastic and tangible effects on trans and nonbinary youth across America. According to the APA, about one-third of all trans and nonbinary youth live in a state that has restricted gender-affirming care. 45% of families with trans or nonbinary children at least considered relocating to a state without restrictions on care. Since restrictions on gender-affirming care began rolling out, severe depression, self-harm tendencies, and suicidal ideation have proliferated among trans and nonbinary youth. In a survey of 18,000 American LGBTQ+ youth conducted by The Trevor Project, 36% reported they had seriously considered suicide in the past year, and within the survey, 46% of all trans persons reported they had seriously considered suicide.

Access to gender-affirming care has lifesaving and immediate effects on the mental and physical wellness of trans and nonbinary people. The long-term benefits of gender-affirming care on mental and physical health are well supported, but a recent NIH study showed that after just 12 months of gender-affirming care, the odds of severe depression and suicidality lowered by 60% and 73%, respectively. Other studies have shown significant decreases in gender dysphoria and exceeding low levels (less than 1%) of regret after beginning hormonal treatments and performing gender-affirming surgeries.

The effects of harmful executive orders from Trump’s office are clear. Claims of protecting children from treatments with negative health consequences are unconvincing when opposed by countless scientific studies and personal anecdotes supporting the value of gender-affirming care. However, Republicans in the House of Representatives have crafted a slew of anti-LGBTQ+ riders, such as provisions attached to spending bills that require federal agencies not to support gender-affirming care. These riders will prohibit federal employees and their families from accessing gender-affirming care, even if Trump’s executive orders are struck down. Therefore, creating public pressure on local representatives is vital to protect gender-affirming care from Congressional overreach.

FTC Seeks to Put a Pin in Insulin Inflation: FTC Sues CareMark, Express Scripts, and OptumRx

The Federal Trade Commission filed another ambitious lawsuit on September 20, 2024, against three major pharmaceutical benefit managers (PBMs) that serve as middlemen between pharmaceutical manufacturers and commercial insurers. The defendants are CVS Health’s CareMark, Cigna’s Express Scripts, and UnitedHealth’s OptumRx, who together control the affordability and accessibility of 80% of prescriptions in the U.S. The FTC’s administrative complaint alleges that the PBMs violated The FTC Act 15 U.S.C. § 45 which prohibits “unfair or deceptive acts or practices in or affecting commerce.” The FTC argues the three PBMs have engaged in unfair practices by creating exclusive drug formularies that favor including drugs with higher rebates and fees which drives insulin inflation and harms vulnerable patients.

Exclusive drug formularies created by PBMs have flipped the pharmaceutical industry competitive market upside down to where competition drives insulin prices upwards, instead of down. Around 2012, PBMs implemented these formularies to ensure covered drugs which they resold to commercial insurers were safe and effective. However, the exclusivity of formularies forced pharmaceutical manufacturers to raise list prices of drugs to maintain their profits while increasing the rebates for PBMs. Manufacturers that do not raise drug prices or offer larger rebates risk losing millions of dollars in drug sales. Therefore, uninsured patients must fund larger rebates by paying increased drug prices or else forgo essential pharmaceutical treatment. Patients are also harmed by PBMs favoring high-list price (usually name brand) drugs when creating their formularies. Because pharmaceutical manufacturers can offer larger rebates for name brand drugs, PMBs exclude cheaper generic drugs to increase their profits. Consequently, insured patients are forced to spend more than necessary for critical drugs which they purchase frequently such as insulin.

Exclusive drug formularies specifically harm diabetic patients who cannot reasonably choose to discontinue purchasing insulin, switch insulin products, or switch health plans to avoid these harmful practices by PBMs. They unfairly force vulnerable patients to bear the financial burden of increasing PBM profits or risk great bodily harm from stopping medication.

Insulin has been used for more than a century to manage diabetic blood sugar levels and has been reasonably priced for 85 years prior to 2012. However, when PBMs began implementing exclusive drug formularies, between 1999 to 2017, prices increased steeply. During this time there was a 1200% increase in the list price of insulin from $21 to $274. U.S. consumer spending on insulin has also tripled since 2012, from $8 billion to $22.3 billion. Insulin is relied upon by 8 million diabetic Americans for disease management and is inexpensive to manufacture, yet its list price is inexplicably and unjustly exorbitant.

Although the Inflation Reduction Act has capped costs for patients with Medicare, increased insulin list prices have harmed uninsured patients. These uninsured diabetics are forced to pay the list price for insulin out-of-pocket. PBMs are aware that approximately one-quarter of patients can no longer afford insulin and reported that 1 million Americans ration their insulin which can have severe consequences, including death.

To be held liable for “unfair acts or practices in or affecting commerce” under The FTC Act, the three PBMs practices must be found to have (1) caused or were likely to cause substantial injury to consumers, (2) not have been reasonably avoidable by consumers, and (3) not been outweighed by countervailing benefits to consumers or to competition. If the three PBMs charged with violation of The FTC Act are found to have used unfair practices when implementing exclusive drug formularies, there are implications for the whole pharmaceutical industry which could hugely reign in drug pricing.

The future of the case against the three PBMs could hinge on the results of the 2024 Presidential election. Vice President Harris has shown interest in holding PBMs accountable for their actions in drug pricing inflation while former President Trump has yet to mention drug price inflation during his 2024 campaign. Further adding to the uncertainty of the suit is the divide among Republican officials over whether the FTC is overreaching, or PBMs should be held accountable.

Regardless of the election results, action is needed to prevent further harm from befalling vulnerable patients forced to pay the full list price for critical drugs like insulin.