Trump's Memorandum on Pharma DTC Advertising is a Solution in Search of a Problem

By: Ranier Simons, ADAP Blog Guest Contributor

Adding to the growing list of edicts issued by the Trump Administration is a presidential memorandum issued in September 2025 regarding prescription drug advertising. The memorandum was not an executive order; thus, it listed no detailed implementation or specified remedy for a perceived problem that probably doesn’t exist. It simply implied that the U.S. Food & Drug Administration (FDA) has not been effective at “protecting the public” from inappropriate direct-to-consumer (DTC) advertising. The memorandum directs the Commissioner of Food and Drugs to enforce the Federal Food, Drug, and Cosmetic Act’s (FD&C Act) prescription drug advertising provisions to ensure pharmaceutical DTC advertising is transparent and non-misleading. While it is laudable to emphasize the need for patient protection, DTC advertising by other industries, including alcoholic beverage companies, also poses significant harm to the public.

Photo Source: BioSpace

In coordination with the release of the presidential memorandum, the FDA also released a press release on the same day (FDA, 2025). The release stated that the FDA would send 100 cease-and-desist letters to pharmaceutical companies using what it described as deceptive ads. Additionally, the release noted the FDA would be initiating rulemaking to close the “adequate provision loophole”, a 1997 FDA regulation regarding disclosures in DTC broadcast advertising. The loophole allowed drug advertisements, particularly DTC broadcast radio and television ads, to be considered compliant if they contained a brief “major risk statement” indicating major side effects and included information directing people to a website or phone number for very detailed drug information. Before 1997, the level of detail required resulted in drug information presentations of the length and breadth of infomercials in order to display a complete safety list of risks and contraindications.

Back in 2023, the FDA had actually already established a final rule specifying advertising requirements to fulfill the major statement requirement in a “clear, conspicuous, and neutral manner” (Craven, 2023). The standards required that:

• The major statement is presented in language and terminology that is consumer-friendly and readily understandable
• Audio information in the major statement is as understandable as audio information in the rest of the ad in terms of volume, articulation, and pacing
• During presentation of the major statement, the ad does not contain audio or visual elements that might interfere with a consumer’s understanding of the content
• During TV ads, the text information is presented in a way that is easy to read
• During TV ads, the major statement is to be presented simultaneously in audio and text, and is shown for long enough to be read easily

Presently, the FDA has issued over 100 untitled letters to various manufacturers regarding specific drug advertisements. The agency lists many of those DTC violation letters on the FDA website under the “untitled letters” and “warning letters” areas. The letters’ claims revolve around a few key ideas. A major complaint is that the advertising makes claims that the cited literature or associated clinical trials do not support. Another purported issue is that the presentation of the subjects indicates a quality-of-life improvement that is not supported by the data. Regarding the presentation, there are letters stating that the on-screen information is too detailed to be read in the brief screen time available. 

Photo Source: US Pharma Marketing

The violation letters are not just targeting patient-facing ads. The FDA is also targeting promotional materials to healthcare professionals (HCP). One letter sent to Amgen Incorporated showed that the Center for Drug Evaluation and Research was not satisfied with the level of detail in the analysis of one of the studies used to support the efficacy and depth of response section of a website dedicated to the drug Imdeltra. The letter complained that outcomes were reported based on a single-arm clinical trial, thus improperly substantiated. A single-arm clinical trial is one in which all subjects receive the same medication under study, without a control or placebo group. A single-arm clinical trial is actually appropriate in several instances. For example, there are some studies conducted where rare diseases are involved; thus, it is unethical to subject participants to placebos for life-threatening conditions (Hembara, 2025). 

The violation letters all state that, due to the stated violation, the distribution of a drug violates the FC&C Act. Thus, an accused entity must file a written response explaining how it will remedy the specifically stated violation or pull a drug from distribution. To date, over 60 enforcement letters have been issued, along with 58 warning letters sent to online pharmacies regarding the promotion of compounded products that seemingly erroneously indicate they are FDA-approved (Propharma, 2025). Presently, there have been no adverse governmental actions in response to any of the letters that have been issued.

The potential final outcome of the FDA’s actions is unclear. No rulemaking has been set regarding the adequate provision loophole. Thus, it is entirely plausible that, at some point, drug manufacturers would have to pull all broadcast DTC advertising in its current form. That would be devastating financially for networks in terms of advertising dollars. Drug manufacturers spent $7.9 billion in television advertising from January to October 2024 (Wolk, 2025). Switching from television to online advertising is not as beneficial for pharmaceutical companies, as older Americans are their audience. Older Americans are heavy consumers of broadcast television and cable news outlets (Wolk, 2025). Thus, if eventually a ban on broadcast DTC advertisements were to occur, networks would take a heavy financial hit.

It also poses a challenge for the network's viewers...patients. Creating artificial barriers has never yielded positive health outcomes, but the presidential memorandum overlooks this for patients. It also artificially targets a single industry while conveniently overlooking or ignoring abuses that truly do exist in television advertising by other industries.

Photo Source: Federal Trade Commission

Conversely, the focus on DTC pharmaceutical advertising in the name of public health ignores the alcohol industry and the food supplement industry. Regarding alcohol, one media data sample estimates that 1.6K companies spent over $1.4 billion on broadcast and digital advertising in 2023, Q4 (Media Radar, 2023). Alcohol advertisements depict a high quality of life and enjoyment for everyone who consumes the beverages. There are no major statements about the adverse medical realities of alcohol consumption. Yet the FDA is not focused on how alcohol ads would indicate that consumption is directly correlated to positive social interactions with no side effects. Alcohol ads also do not have disclaimers to raise concern about the interaction between alcohol and a person’s prescription drugs, health supplements, or contraindicated pre-existing health conditions, or addiction. 

No concrete legal rulings on DTC drug advertising are expected in the near future. The government is not only in a shutdown but is already operating at a diminished capacity, given the administration’s elimination of 3,500 FDA jobs earlier this year (Frank & Glied, 2025). Moreover, any future rulemaking or aggressive penalty pursuit will be followed by lawsuits. Most importantly, bona fide patient harm from DTC pharmaceutical advertising has not been proven. Drug advertising, in some ways, increases patient access by bringing awareness to disease states and therapy modalities. Time will tell whether the FDA's actions are performative politics or a means to a beneficial end.

[1] Craven, J. (2023, November 21). FDA issues new standards for DTC prescription drug ads. Retrieved from https://www.raps.org/news-and-articles/news-articles/2023/11/fda-issues-new-standards-for-dtc-prescription-drug

[2] Frank, R., Glied, S. (2025, May 14). The Trump administration’s NIH and FDA cuts will negatively impact patients. Retrieved from https://www.brookings.edu/articles/the-trump-administrations-nih-and-fda-cuts-will-negatively-impact-patients/#:~:text=The%20Trump%20administration%20has%20made%20unprecedented%20cuts,biological%20products%20*%20Develop%20competitive%2C%20lower%2Dpriced%20products

[3] Hembara, N. (2025, January 13). Single Arm Studies: What Are They & When Are They Used? Retrieved from https://www.allclinicaltrials.com/blog/what-are-single-arm-studies

[4] Media Radar. (2023, December 26). Q4 2023 12 for ‘24 - Alcohol. Retrieved from https://www.mediaradar.com/blog/blog/q4-2023-12-for-24-alcohol.

[5] Propharma. (2025, October 28). FDA Tightens the Reins on DTC Drug Ads: Big Picture Insights and Industry Implications. Retrieved from https://www.propharmagroup.com/thought-leadership/insights-fda-2025-enforcement-letters-ccn-standards

[6] U.S. Food & Drug Administration (2025, September 9). FDA Launches Crackdown on Deceptive Drug Advertising. U.S. Department of Health & Human Services. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-launches-crackdown-deceptive-drug-advertising

[7]7 Wolk, A. (2025, March 4). Could A Pharma Ad Ban Shake Up The TV Industry? Retrieved from https://www.tvrev.com/news/could-a-pharma-ad-ban-shake-up-the-tv-industry#:~:text=Pharmaceutical%20advertising%20has%20long%20been,and%20they%20aren't%20pretty.

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.    

Fraudsters are Using Grindr to Buy HIV Meds

By: Brandon M. Macsata, CEO, ADAP Advocacy; Shabbir Imber Safdar, Executive Director, Partnership for Safe Medicines

Earlier this year, ADAP Advocacy, in collaboration with the Partnership for Safe Medicines (PSM),  issued an important safety alert warning Grindr's users to stop selling their HIV and other medications on the popular gay dating App. Medicine buyback schemes falsely claim to be "Buyers Clubs" making medicine available to people who cannot afford them. In reality criminals buy medicine, and sometimes empty bottles, from patients and sell them at a discount to unsuspecting pharmacies who dispense it to patient victims. The safety alert urged Grindr's users to be more mindful of patient safety.

Photo Source: ADAP Advocacy

Grindr, as well as potentially other dating Apps, are being used as a platform for fake user profiles operating under counterfeit drug rings to buy prescription medications. This seemingly innocent practice is not only illegal, but it is jeopardizing the drug supply chain and putting the health of patients at risk for health complications, severe illness, and even death. It often targets high-cost drugs – because the potential profit spread is higher – often associated with the treatment of cancer, diabetes, and HIV (and others).

This is not a theoretical patient danger: over the past five years, hundreds of millions of dollars of HIV medicine has been diverted and counterfeited in the drug supply this way, resulting in some patients getting fake medicines. 

ADAP Advocacy and PSM potentially uncovered one such counterfeit drug ring in New Orleans Parish earlier this year and immediately alerted both the U.S. Food & Drug Administration, as well as Gilead Sciences. Earlier this year, Gilead Sciences uncovered a criminal enterprise centered in Florida distributing over $230 million of counterfeit drugs, some of which were their HIV antiretroviral medications.

In response to the Florida fraudsters, ADAP Advocacy and PSM aired a public service announcement sharing some important steps patients can take to combat counterfeit drugs. Additionally, PSM hosted an online briefing focused on recent breaches in the United States drug supply chain that put patients living with HIV at risk.

If you see people trying to buy medicine on dating apps, please report them to us.

• REPORT FRAUDSTERS by filling out this webform
• By emailing us at report@safemedicines.org
• By texting us at (415) 367-0067.

Additional collaboration on patient safety in the fight against counterfeit drug rings is warranted in this space. Download the safety alert, here.

Photo Source: ADAP Advocacy

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.

Drug Shortages Growing, but Spares HIV-related Injectable Therapies

By: Ranier Simons, ADAP Blog Guest Contributor

Periodic shortages of all kinds of products are common. The height of the coronavirus pandemic even created a widespread shortage of toilet paper, Lysol, and baby formula. At times, drug shortages are also not uncommon. Nevertheless, drug shortages have been a trending topic in the media. The heightened discourse is atypical for so many drugs to be experiencing shortages simultaneously. Not only are there many drugs in shortage, but they have been in scarcity for a long time. Moreover, some of the drugs in shortage treat life-threatening conditions. Now shortages appear to be impacting injectable therapies.

Photo Source: Forbes

Drug shortages have increased over time, with the end of 2023 being the highest in the past ten years. At the end of 2025, according to the U.S. Food & Drug Administration (FDA), 125 drugs were in shortage status. Some of the drugs were new to the shortage list. However, many have been in shortage status for years. Furthermore, the duration of shortage status has also been increasing. In 2023, the average shortage was about three years compared to a duration of two years in 2020.[1] Unfortunately, at 2023 year-end, about a quarter of the drugs on the list had been in shortage for approximately five years, and treatments such as epinephrine injections had been in shortage for over ten years.[1,2]

Drug shortages affect all aspects of healthcare. No one therapeutic class is disproportionately harmed. Clinicians are frustrated because shortages of life-saving medications endanger many living with life-threatening conditions. Complete outages of supply mean that some patients must suffer through dangerous delays in care. In other cases, doctors must switch regimens completely due to shortages, forcing them to use medications they do not feel are the best options for patients. This results in using less efficacious medications with poorer desired outcomes and undesirable side effects. Additionally, when shortages result in switching from a regimen in progress, there is a danger of the body becoming unresponsive to the original regimen when the shortage is resolved.

A myriad of issues create drug shortages. Some of those issues are economic, supply and demand, and even manufacturing quality problems. Shortages are more common with lower-priced drugs such as generics.[3] A prescription for most of the injectables and solid oral medications in shortage costs less than five dollars to produce.[1,2] This translates into meager manufacturer profit margins, especially with wholesalers and purchasing groups driving down pricing. Thus, manufacturers are not incentivized to produce those medications in sustained large quantities. The FDA cannot force a company to make a particular medication, even if it is needed.

Photo Source: FDA

Supply and demand issues also drive shortages. In some cases, demand outpaces supply when drugs are used for expanded use cases. This is the case for drugs like Ozempic and Wegovy, which are GLP-1 drugs whose primary indications are to treat diabetes. The discovery of its effectiveness in weight loss has resulted in a vastly increased demand. The demand driven by the population of those dependent upon GLP-1 drugs to manage diabetic conditions in combination with those using them for weight loss has driven outages as well as increased pricing. Some of the demand for other drugs is driven by increases in prescriptions due to telemedicine. During the pandemic, restrictions were lifted on the prescribing of certain classes of medicines via telemedicine, such as Adderall, which is used for ADHD.[4] This resulted in increased demand for the drug which contributed to shortages that are still seen presently. This is especially pertinent since some obtain Adderall and other medications online for purposes of substance abuse.

Manufacturing problems and supply chain issues strongly contribute to drug shortages as well. The U.S. is dependent upon sources outside of the country for many of the drugs in shortage status. Less than one-quarter of the oral generics used in the U.S., and about 40 percent of sterile injectable generics are manufactured domestically. Approximately 17% of injectables used in the U.S. are manufactured in China.[5] Most importantly, many of the raw ingredients for pharmaceuticals are sourced outside of the U.S., with materials for 90-95 percent of U.S. generic injectable drugs coming from China and India.[5,6] Manufacturing certain older generic drugs, especially sterile injectables, is difficult due to the sterile manufacturing conditions required; thus, the number of capable facilities is low.

About 53 percent of the newest drug shortages are generic injectable medicines.[7] Sterile injectables include normal saline, antibiotics, flu vaccines, chemotherapy drugs, morphine, and insulin. Shortages in chemotherapy drugs have caused doctors and hospitals to resort to drug rationing. In those instances, hard decisions must be made regarding the treatment of life-threatening cancers. Doctors must choose which patients receive certain medications based on decisions based on curative intent and probability versus overall survival.

Photo Source: ADAP Advocacy

Drug shortages were also of heightened concern for those living with HIV during the coronavirus pandemic. In March 2020, ADAP Advocacy received assurances directly from each drug manufacturer that the coronavirus pandemic wasn’t negatively impacting the availability of anti-retroviral medications. The pharmaceutical industry was applauded for its efforts to protect the anti-retroviral drug supply chain.[8] At that time all of the drug manufacturers – AbbVie, Janssen Pharmaceuticals, Gilead Sciences, Merck. Theratechnologies, and ViiV Healthcare – did not foresee disruption to their supply chain.

Considering injectable therapies are increasingly showing up on the FDA’s drug shortage list, ADAP Advocacy once again inquired with its industry partners about potential concerns over shortages of injectable HIV-related medications, such as the injectables Cabenuva for the treatment of HIV, and Sunlenca for the prevention of HIV. 

Reaching out to the industry resulted in very positive feedback. A representative from ViiV Healthcare stated that “there are no current shortages nor anticipation of any prolonged shortages of any injectable within the ViiV portfolio.”

A Gilead spokesperson likewise stated, “Gilead’s commercial supply chain is robust, and we have a strong inventory position. We continually monitor the forecast and actively manage supply; thus, we do not anticipate any supply concerns related to Sunlenca®, Gilead’s twice-yearly injectable HIV treatment option for people living with the virus who are heavily treatment-experienced with multi-drug resistant HIV. We are committed to person-centric HIV treatment research and development, ensuring our advances in biomedical innovation reach the wide range of individuals and communities who are most in need.” 

Drug shortage is a serious concern that will require a multi-pronged approach to solve. The White House, FDA, and others must find solutions to the manufacturing, regulatory, and supply chain challenges. The government is already looking into investing in some of the raw materials needed for drug creation, which is a good start.

[1] Lokuwithana, D. (2024, June 15). U.S. drug shortages worsen to reach a decade high: report. Retrieved from https://seekingalpha.com/news/4116477-us-drug-shortages-reach-decade-high

[2] Silverman, E. (2024, June 4). U.S. drug shortages have reached a decade high and are lasting longer, too. Retrieved from https://www.statnews.com/pharmalot/2024/06/04/shortages-medicines-drugs-hospitals-manufacturing-cancer-adhd-gpo/

[3] IQVIA. (2023, November 15). Drug shortages in the U.S. 2023. Retrieved from https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/drug-shortages-in-the-us-2023

[4] Gilbert, D., Amenabar, T. (2023, March 14). An Adderall shortage has not let up. Here is why. Retrieved from https://www.washingtonpost.com/business/2023/03/14/adderall-shortage-telehealth-prescriptions/

[5] Owens, C. (2024, January 5). Low prices are contributing to America's drug shortage problem. Retrieved from https://www.axios.com/2024/01/05/america-generic-drug-shortage-reasons

[6] United States Senate Committee on Homeland Security and Governmental Affairs. (2023, March). Short Supply: The Health and National Security Risks of Drug Shortages. Retrieved from https://www.hsgac.senate.gov/wp-content/uploads/2023-06-06-HSGAC-Majority-Draft-Drug-Shortages-Report.-FINAL-CORRECTED.pdf

[7] U.S. Pharmocopeia. (2024, June). USP Annual Drug Shortages Report. Retrieved from https://go.usp.org/l/323321/2024-05-31/92zsjg/323321/1717187146zgOpt4vW/GEA_GC_056R_MSM_Report_2024_05_FINAL.pdf?_gl=1*e6c4sj*_gcl_au*Mjc1NzUzOTg5LjE3MTc1MTMzOTM.*_ga*OTI0OTQ1ODI4LjE3MTc1MTMzOTM.*_ga_DTGQ04CR27*MTcxNzUxMzM5My4xLjEuMTcxNzUxMzc1Ny4wLjAuMA

[8] ADAP Advocacy. (2020, March 26). Press Release: ADAP Advocacy Association Applauds Pharmaceutical Industry Efforts on Protecting the Drug Supply Chain during the Coronavirus Pandemic. Retrieved from https://www.adapadvocacy.org/pdf-docs/2020_ADAP_Press_COVID_19_Supply_Chain_03-26-20.pdf

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.  

What are 'Major Statements' for Direct-to-Consumer Pharmaceutical Advertisements

By: Ranier Simons, ADAP Blog Guest Contributor

In the United States, it is common to see advertisements for drugs. Ads appear in print magazines, on television, on the radio, on the internet, and mobile devices. In 2022, the pharmaceutical industry spent nearly $17.4 billion on advertising.[1] The majority of this spending is direct-to-consumer pharmaceutical advertisement (DTCPA) spending. Coincidentally, the United States and New Zealand are the only countries in the world allowing DTCPA. Other countries have banned DTCPA because they feel it does more harm than good. In addition to well-established prescription drug advertising regulations, the U.S. Food & Drug Administration (FDA) released a final rule in November of 2023, effective as of May 20, 2024.[2] Companies have until November 20, 2024, to come into full compliance. 

Photo Source: FDA

The new rule is specific to DTCPAs that are delivered in radio or television format, which name a drug and describe what it is used for. This rule focuses on the presentation of the ‘major statement’, which is the explanation of a drug's side effects and contraindications. There are five key standards the rule establishes. Major statements must be delivered in consumer-friendly language; audio information must be understandable; text must be presented clearly, conspicuously, and neutrally; text information must be readable; and ads cannot include distractions.

Requiring statements to be delivered in consumer-friendly language means that information regarding a drug's side effects and contraindications does not contain scientific and medical jargon. Most consumers must easily understand it. The rule’s requirements concerning the audio information are a direct response to the way ads used to appear and sound. Audio must be understandable in terms of volume, articulation, and pacing.[2] Previously, ads, whether on television or radio, would list a long line of side effects and concerns with a rapid cadence and sometimes in a less audible tone than the rest of the advertisement. This is because ads were required to list almost every possible side effect of a medication. The new rules now mean that only the major and most frequent side effects must be stated. They must be articulated in audio that is as clear as the remainder of the advertisement.[2]

With respect to text, the rule explains that textual information must be presented in an appropriate font, positioned in a visually advantageous manner, against an appropriately contrasting background, and appear for a proper duration of time.[2] Regarding distractions, the rule explains that ads cannot contain statements, text, images, or sounds that distract from the communication of the major statement of side effects and contraindications.[2] Most importantly, in terms of transparency, the contents of the major statement have to appear simultaneously in the audio and video portions of television ads, which is referred to as dual-modality.[2]

The new rule, in addition to the longstanding advertisement regulations, is meant to protect consumers and ensure they are not misled about what drugs can and cannot do. It also informs them about a medication’s risks. Many critics feel the new rules do not go far enough, primarily since they do not address the content of the information, only its presentation.

Photo Source: FDA

There are many pros and cons to DTCPA. Advertisements can educate patients about available treatment options, encourage people to seek care, especially regarding underdiagnosed conditions, and improve communication between doctors and patients. Moreover, when someone sees an ad for a drug they are already taking, it can be a reminder to take their medication as well as positively influence how they feel about the medication, which can increase adherence. Negative attributes of DTPCA are it can lead to overuse of some prescription drugs, which increases drug spending, can cause higher utilization of brand name drugs instead of effective lower-cost generics, and can negatively affect the patient-doctor relationship.[3] Consumers may see an advertisement for a drug and demand it from their physician. However, the physician may deny them a particular medication because the physician is knowledgeable of medical reasons why a drug may not be a good fit or actually be harmful. This could affect the trust and communication between a doctor and a patient.

A notable shift regarding DTCPA is regarding drugs to treat and prevent HIV/AIDS. Over the past few years, there has been a recognizable increase in the number of ART-related television, print, radio, and digital ads. In 2021, ads for ART accounted for six percent of total prescription drug ad spend. Gilead Sciences and GSK accounted for almost all of 2021’s pharmaceutical ad spending dedicated to HIV and AIDS.[4] For example, GSK spent all its 2021 Q4 advertising budget buying spots on ABC, A&E, CBS, CNN, Fox, NBC, and the USA network, which was 75% of what the company spent on television ads that year.[4]

ViiV Healthcare, which is majority-owned by GSK, with Pfizer Inc. and Shionogi & Co. Limited (Shionogi) as shareholders, has had a recognizable presence in television ads since 2017. In 2017, one of its first significant television campaigns was for Triumeq.[5] In 2022, ViiV spent $8.3 million in June alone, on television ads for Dovato. Advertisements for HIV-related drugs on television, in print ads, and digital forms are potentially not just beneficial for drug companies’ bottom lines.[6]

Photo Source: Trend Radars

Antiretroviral drug ads are educational in informing patients of drug options. The science behind treatment for HIV/AIDS is moving at a rapid pace, and many are not aware of all the treatment options available. Advertisements can empower HIV/AIDS patients to have discussions about treatment modalities their doctors may not have presented to them. Additionally, antiretroviral drug campaigns are a kind of social engineering. There are still negative perceptions and public stigma surrounding HIV despite scientific knowledge supporting the concept of undetectable viral load translating into a lack of risk of transmission, or “U=U undetectable = untransmittable.”[6] Many television ads depict subjects who are actual users of the antiretroviral medications, publicly revealing their status. This can add humanity to a disease that remains cloaked in stereotypes and misinformation for many.

Whether in a magazine, a television commercial, a print ad, a YouTube video, or a digital mobile pop-up, pharmaceutical advertisements in the United States are here to stay. There are valid pros and cons. The only way to ensure that the pros outweigh the cons is to monitor and regulate intentionally. Difficulties in the logistics of enforcing governmental regulations can mean slow adoption of and even violation of rules. Optimistically, the efforts of consumers, advocates, and medical professionals can facilitate acceptable and effective pharmaceutical advertisement utilization and execution.

[1] Faria, J. (2023, September 22). U.S. pharmaceutical preparations ad spend 2021-2022. Retrieved from https://www.statista.com/statistics/470460/pharmaceutical-preparations-industry-ad-spend-usa/#:~:text=In%20a%20survey%20of%20representatives,billion%20U.S.%20dollars%20on%20advertising.

[2] FDA. (2023, November 21). Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format. Retrieved from https://www.federalregister.gov/documents/2023/11/21/2023-25428/direct-to-consumer-prescription-drug-advertisements-presentation-of-the-major-statement-in-a-clear

[3] Keller, J., Hauschild, J. (2024, January 10). FDA Issues Final Rule and FAQ Regarding Direct-to-Consumer Drug Advertising. Retrieved fromhttps://www.faegredrinker.com/en/insights/publications/2024/1/fda-issues-final-rule-and-faq-regarding-direct-to-consumer-drug-advertising

[4] Media Radar. (2022, May3). HIV/AIDS Prescription Drug Advertising: Looking Toward the Future. Retrieved from https://mediaradar.com/blog/hiv-aids-prescription-drug-advertising/

[5] Bulik, B. (2017, December 4). ViiV starts 'Moving Forward' into first branded TV ads for HIV treatment. Retrieved from https://www.fiercepharma.com/marketing/viiv-s-first-branded-hiv-tv-ad-stars-real-patients-and-their-stories

[6] Adams, B. (2022, July 11). ViiV wants HIV patients to 'detect this' as it launches new Dovato TV ad. Retrieved from https://www.fiercepharma.com/marketing/viiv-wants-hiv-patients-detect-it-launches-new-dovato-tv-ad

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.  

Evidence Suggests Long-Acting Injectables Game Changer for Adherence

By: Ranier Simons, ADAP Blog Guest Contributor

Adherence to medication is one of the most important tenets of antiretroviral therapy (ART) for people living with HIV (PLWH). Adherence is taking the appropriate medications in the proper dosages on the correct schedule. Reaching an undetectable viral load requires strict adherence, with which many PLWH have difficulty for various reasons. The recent innovation of long-acting injectables (LAI) is an attempt to strengthen adherence for PLWH who have difficulty with pill regimens. In January 2021, the U.S. Food & Drug Administration (FDA) approved Cabenuva, the first injectable drug combination for HIV.[2,5] GSK recently released results from clinical trial data indicating Cabenuva works better than daily pills for patients with adherence challenges.[1,4,5,6]

Photo Source: Pharmalive

Cabenuva is a two-injection regimen of cabotegravir and rilpivirine administered either once a month or once every two months.[7] This month, GSK released data from the LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) study comparing the efficacy of Cabenuva in contrast with daily pill regimens regarding adherence.[1] The screened participants were verified as having challenges with ART adherence. They were initially given a three-drug oral ART regimen, receiving comprehensive and incentivized adherence support.[1] Once they were virally suppressed, they were randomly selected to receive Cabenuva injections every four weeks or continue with daily pill therapy.[1] The strong evidence of superior efficacy of Cabenuva over daily pill therapy led the Data Safety Monitoring Board (DSMB) for Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) to recommend removal of the randomization and offer all participants the option to take Cabenuva.[1]

This new development is an optimistic win in the fight against HIV. Joey Wynn, activist and chair of the ADAP Long-Acting Injectables Patient Advisory Committee, states, “Although definitely not for everyone, this is the next phase of evolution in HIV therapy. Injections allow us to get on with our lives and not be weighed down with the daily burden of taking pills.” 

There are many reasons daily pill therapy adherence is a challenge for some. Psychologically, taking daily pills is a reminder of disease that is too much for some to handle. There are people with developmental challenges who can't keep up a daily regimen. Stigma and privacy are adherence challenges for PLWH in living situations that are not safe or supportive, where the discovery of medication bottles is not ideal or dangerous.[2,3]

Photo Source: NIAID

As Riley Johnson, project manager for ADAP Advocacy's Long-Acting Injectables Project, points out, “LAIs can mean consistent medication instead of having meds lost or stolen and having to navigate bureaucratic hoops to pursue replacement.”

While very promising, Cabenuva does have hurdles to its implementation. Presently, there are three main criteria to be eligible for Cabenuva. It is only approved for PLWH who are virally suppressed, have documented absence of resistance to either cabotegravir or rilpivirine, and have no prior antiretroviral treatment failures.[2] Viral suppression requires adherence to oral medication, which is the challenge LAIs were created to remedy. In 2019, the Centers for Disease Control & Prevention (CDC) estimated that only 56.8% of PLWH were virally suppressed or undetectable.[2] This means that less than half of PLWH in the U.S. would qualify for Cabenuva. 

Just as with pill regimens, cost is also a hurdle for widespread adoption. The wholesale acquisition cost of the initial/loading dose is $5,940, and monthly/maintenance injections are $3,960.[5] Insurance companies must approve Cabenuva before patients can begin therapy. This is an access issue for those who do not have medical insurance. It is also an access issue for those with insurance because some insurance companies do not have an official classification of Cabenuva as a pharmaceutical or healthcare benefit. Thus, even though ViiV Healthcare has a payment assistance program for those who have commercial insurance, the lack of clarity of benefit status means ambiguity in which costs will be billed to patients and which to insurance companies.[2]

Studies have shown that multiple social determinants of health affect many patients' ability to maintain adherence regarding pill regimens. The same challenges apply to Cabenuva. Cabenuva must be administered in a healthcare setting by a health professional. Even though the visits would only be monthly or bi-monthly, that still poses a challenge for PLWH who lack reliable and affordable transportation. While pill forms of the medications are available for emergency doses if a patient misses an injection, on-time injections of Cabenuva are imperative to ensure resistance to either of the components does not occur.[2] Shipping doses of emergency medication is not viable for people with unstable housing or living situations where receiving medication is not optimal.

Photo Source: HIV.gov

Widespread adoption of Cabenuva also requires providers to adopt changes. Currently, with HIV healthcare, patients on established therapy only see their infectious disease doctors once or twice a year, and the responsibility of pill treatment adherence is on the patient. With Cabenuva injections, the facility's operational flow is disrupted since the injections require more frequent visits. Additionally, responsibility is added to the medical practices by ensuring patients do not miss their injection appointments and following up with them when they do. Moreover, practitioners must be trained in the z-track injection technique required for the intramuscular injection and have proper refrigeration equipment to store the Cabenuva between 2°C and 8°C.[8]

The recent data from the Cabenuva trial is a promising step in the right direction, though not without its challenges. Joey Wynn adds, “Understandably, there are issues of access for those on private insurance, clinic flow issues, and limited distribution shortages, meaning advocates need to demand improved pipeline delivery from the manufacturer so people can get what they need/want/require with less difficulties.” Riley Johnson adds, “no degree of adherence is possible if the medication is not available or accessible.” To ensure the success of the LAI landscape, policy and holistic community support will be required to keep up with the advances of science.

[1] GSK. (2024, February 21). Press release: LATITUDE phase III interim trial data indicates ViiV Healthcare’s long-acting injectable HIV treatment Cabenuva (cabotegravir + rilpivirine) has superior efficacy compared to daily therapy in individuals living with HIV who have adherence challenges. Retrieved from https://www.gsk.com/en-gb/media/press-releases/latitude-phase-iii-interim-trial-data-indicates-cabenuva-has-superior-efficacy-compared-to-daily-therapy/

[2] Pinto, R. M., Hall, E., & Tomlin, R. (2023). Injectable Long-Acting Cabotegravir-Rilpivirine Therapy for People Living With HIV/AIDS: Addressing Implementation Barriers From the Start. The Journal of the Association of Nurses in AIDS Care: JANAC, 34(2), 216–220. https://doi.org/10.1097/JNC.0000000000000386

[3] Simoni, J. M., Tapia, K., Lee, S. J., Graham, S. M., Beima-Sofie, K., Mohamed, Z. H., Christodoulou, J., Ho, R., & Collier, A. C. (2020). A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S. AIDS and Behavior, 24(4), 1226–1236. https://doi.org/10.1007/s10461-019-02701-7

[4] Hart, R. (2024, February 21). First long-acting injectable HIV treatment works better than daily pills for some patients, GSK says. Retrieved from https://www.msn.com/en-us/health/other/first-long-acting-injectable-hiv-treatment-works-better-than-daily-pills-for-some-patients-gsk-says/ar-BB1iDCzR?ocid=socialshare

[5] Bernstein, L. (2021, January 22). FDA approves breakthrough injectable HIV medication. Retrieved from FDA approves breakthrough injectable HIV medication

[6] Liu, A. (2024, February 21).GSK’s long-acting HIV med Cabenuva beats daily therapy in patients who've faced adherence hurdles. Retrieved from https://www.fiercepharma.com/pharma/cabenuva-trial-modified-gsks-long-acting-hiv-med-beat-daily-therapy-patients-adherence

[7] VIIV Healthcare. (2024, January). Cabenuva. Retrieved from https://www.cabenuva.com/  

[8] De Vito, A., Botta, A., Berruti, M., Castelli, V., Lai, V., Cassol, C., Lanari, A., Stella, G., Shallvari, A., Bezenchek, A., & Di Biagio, A. (2022). Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort. Journal of personalized medicine, 12(2), 188. https://doi.org/10.3390/jpm12020188

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates. 

FDA Failure: Why Agency's Approval of Floridian Drug Importation Plan Fails Patients on Both Sides of the Border

By: Ranier Simons, ADAP Blog Guest Contributor

The U.S. Food & Drug Administration (FDA) has started the year off in the news cycle under controversy. The beleaguered federal agency announced on January 5th its authorization of Florida’s flawed drug importation program.[1] Under section 804 of the Food, Drug, and Cosmetic Act (FD&C Act), the FDA created a pathway for states to import certain prescription medications from Canada.[2] A state must submit a section 804 importation program proposal (SIP) to the FDA, which fulfills all requirements specified by the FD&C Act and FDA regulations delineated under the Code of Federal Regulations Title 21 Part 251 (21 C.F.R. part 251).[3] Drug prices in Canada are significantly lower than those in the United States, but rooted in a myriad of reasons. The goal, in theory, is to lower the costs of drugs for the consumer by purchasing them at lower prices from Canada. However, Florida’s SIP does not provide lower costs for consumers, threatens the safety of the United States' drug supply, and could cause harm to Canadians. Moreover, in its current approved iteration, Florida’s plan is an acute threat to people living with HIV (PLWH) since many of the proposed drugs for import are HIV treatments. For that reason, ADAP Advocacy was the very first patient advocacy organization to question the FDA's decision after it was made public.

All of the FDA and FD&C Act rules for the importation of prescription drugs from Canada exist to support one central overarching tenet: to significantly reduce the cost of drugs to the American consumer without imposing additional risk to public health and safety. Florida’s plan does not fulfill that tenet. According to Florida’s SIP, the drugs purchased are for those receiving care through the Florida Agency for Healthcare Administration and its Medicaid managed care plans, Agency for Persons with Disabilities (APD), Department of Children and Families (DCF) mental health treatment facilities, Department of Corrections (DOC), and the Department of Health (DOH) county health departments.[4] Those served by these entities are a small subset of the overall Floridan population. Additionally, those receiving prescription drugs through these programs already have access to them at very deep discounts and, in some cases, for free. Any resulting cost savings would benefit state drug spending expenditures, not Floridian consumers.

Cost savings or cost containment is also a challenge due to the logistics required to properly execute the importation program. The section 804 importation program rules require many steps to help ensure the safety of imported medications. One of these critical steps is testing. Testing of every batch of imported medicines is required to verify authenticity, degradation inquiry, and purity to rule out contamination and more.[2,3,5] Testing is expensive and requires the usage of FDA-acceptable testing laboratories. Florida plans to use two testing facilities, one mainly functioning as a backup. One is in Detroit, Michigan, and the other is in Fairfield, New Jersey.[4] There is only one FDA-approved U.S. Customs and Border Protection (CBP)port of entry for eligible imported drugs, which is in Detroit.[4] Thus, there are costs associated with temperature-controlled transport of medications to testing facilities.

Photo Source: US Times Mirror

The costs are just a fraction of the multitude of costly logistical details on both sides of the Canadian border required to implement Florida’s importation plan. The state has a $38 million contract with a logistics company for the administration and operation of the program.[6] This cost is in addition to paying for the drugs purchased under the program. Not only are most Floridians not receiving any consumer relief from prescription drug costs, but as taxpayers, their money is paying for the program. Research by Dr. Kristina M.L. Acri revealed that costs associated with conducting proper testing of imported drugs cancel out any potential savings.[7]

The logistics of implementing the program is also part of why it has the potential to add risk to public health and safety. Section 804 and the FDA regulations stipulate extensive and detailed requirements such as reporting on the origin of medications and their manufacturing, the documentation of the controlled chain of custody of drug batches, verifying that all Canadian suppliers receive drugs from FDA-approved manufacturers, and even requiring a detailed system for notification and retrieving drugs that have been recalled. Proper execution requires many moving parts and geographical locations, providing multiple points of possible compromise. The massive implementation will also result in subcontracting for various aspects, posing another potentially disastrous failure that can result in counterfeit medications, lowered efficacy of drugs due to improper storage or transport, or even adulterated or tampered medications. Moreover, Canada does not have a track and trace system like the United States; thus, there is no solid way to verify true transparency back to a non-US manufacturer.[8]

On the other side of harm is the damage Florida’s drug importation program could potentially be due to the Canadian system. Lyne Fortin, B.Pharm, MBA, who serves on ADAP Advocacy's board of directors, offered her insights from the Canadian perspective: "In recent years, 1 in 5 approved prescription drugs in Canada have been in out-of-stock situations, creating already enormous pressure on the public Canadian Healthcare which continues to introduce regulatory safeguards against US drug importation initiatives. The recent FDA decision, however, paving the way for such a program in Florida dangerously compounds the risks and severity of potential drug shortages for Canadians. Florida alone represents half of the entire Canadian population. HIV being a chronic, life-threatening infectious condition where U=U, the importance of secured supply and drug integrity are even more heightened. When patients on both sides of the border bear all the risks against the pursuit of unvalidated economic benefits, flags should be raised to balance short-sighted wishful thinking policies."

Photo Source: AARP

On January 8th, Health Canada, Canada's version of the FDA, released a statement in response to the FDA decision. “Regulations have been implemented under the Food and Drugs Act to prohibit certain drugs intended for the Canadian market from being sold for consumption outside of Canada if that sale could cause, or worsen, a drug shortage in Canada. This includes all drugs that are eligible for bulk importation to the United States, including those identified in Florida's bulk importation plan or any other state's future importation programs.”[9] Canada is effectively legislatively blocking the bulk exportation of drugs. Essentially, no wholesaler in their legitimate supply chain can ship to the United States, and FDA regulations do not allow imported drugs outside of the legitimate supply chain. Additionally, manufacturers that sell their patented medications in both United States. and Canadian markets will not sell extra supplies to Canada just to potentially buffer increased demand due to exportation. Thus, if any exportation occurred, it would be from the supply meant explicitly for Canada, directly shorting their coffers. Canadians, in general, aren't too happy with the news either!

In addition to the aforementioned problems associated with the Florida bulk importation program, it poses a targeted threat to PLWH. Of the fourteen initial drugs listed for procurement in the Florida SIP, ten are HIV treatment medications. In recent years, there have been issues with counterfeit HIV medications. Gilead Sciences was the victim of a notable scheme. Over a two-year period, criminals sold over $250 million of counterfeit bottles of their HIV drugs including Descovy, Genvoya and Biktarvy.[10] Anything that can threaten the already fragile supply chain of HIV medication, such as drug importation, is a detriment to both U.S. and Canadian public health.

The FDA’s approval of Florida’s SIP is just the first step and one hill the state must climb to actually see any medicine in hand from this program, much less any savings. Additionally, given that Canada is not supportive of the venture, Florida does not have a Canadian supply to tap. Ultimately, the more significant issue is that importation does not solve the United States problem of high prescription drug prices.

[1] FDA. (2024, January 5). News Release: FDA Authorizes Florida's Drug Importation Program. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-authorizes-floridas-drug-importation-program

[2] FDA. (2024, January 5). Importation program under section 804 of the FD&C Act. Retrieved from https://www.fda.gov/about-fda/reports/importation-program-under-section-804-fdc-act

[3] National Archives and Records Administration. (2024, January 10). Code of Federal Regulations: Part 251 - Section 804 Importation Program. Retrieved from https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-251

[4] State of Florida. (2023, October 20). The State of Florida’s Section 804 Importation Program (SIP) Proposal for the Importation of Prescription Drugs from Canada. Retrieved from https://www.safemedicines.org/wp-content/uploads/2019/09/01-Florida-SIP-Proposal-Oct-2023.pdf

[5] FDA. (2024, January 5). Letter of Authorization for Florida’s Section 804 Importation Program. Retrieved from https://www.fda.gov/media/175237/download?attachment

[6] State of Florida Agency for Health Care Administration. (December 29, 2020) Standard Contract. Retrieved from https://www.safemedicines.org/wp-content/uploads/2024/01/CN-680000-ME214.pdf

[7] Lybecker, K. M. (2020). State pharmaceutical importation programmes: an analysis of the cost‐effectiveness. Journal of Pharmaceutical Health Services Research, 11(2), 117–126. https://doi.org/10.1111/jphs.12349

[8] The Partnership for Safe Medicines. (2023). Canada doesn't have Track and Trace. Retrieved from https://www.safemedicines.org/wp-content/uploads/2019/09/Track-and-Trace-final.docx.pdf

[9] Health Canada. (2024, January 8). Statement from Health Canada on FDA decision on Florida bulk drug importation plan. Retrieved from https://www.canada.ca/en/health-canada/news/2024/01/statement-from-health-canada-on-fda-decision-on-florida-bulk-drug-importation-plan.html

[10] Reuters. (2022, September 28). Gilead widens battle against alleged counterfeit HIV drug ring. Retrieved from https://www.reuters.com/business/healthcare-pharmaceuticals/gilead-widens-battle-against-alleged-counterfeit-hiv-drug-ring-2022-09-29/

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.

New Study Dissects Efficacy of Lenacapavir

By: Ranier Simons, ADAP Blog Guest Contributor

Lenacapavir, a novel HIV treatment medication, again appears in the medical news cycle. A recent article in Medical Express, ‘FDA approves treatment for multi-drug resistant HIV,’ was published on September 1st.[1] The article title would lead the reader to think the drug was just approved. However, the U.S Food and Drug Administration (FDA) initially approved lenacapavir in December of 2022.[2] Gilead Sciences released the medication under the name Sunlenca. Please view the previous ADAP Advocacy discussion of Sunlenca and its background here. So, what happened?

Photo Source: sunlencahcp.com

The impetus for the recent article is newly reported data regarding lenacapavir’s ongoing clinical trials. The August 2023 issue of The Lancet included the story, 'HIV presents an article where researchers discuss week 52 results of the phase 2/3 trial',[3] which discusses the study's results. But just as important is examining the study’s design.

The ongoing clinical trial of lenacapavir is also known as the Capella study, ClinicalTrials.gov number NCT04150068. There are 72 subjects divided into two cohorts. Previous data had been reported for evaluations performed at 26 weeks. In Cohort 1, 36 subjects were randomly assigned oral lenacapavir or placebo on days 1,2, and 8 in addition to simultaneously continuing their failing antiretroviral therapy for 14 days. On day 15, those in the lenacapavir group began subcutaneous lenacapavir once every six months (26 weeks) in addition to an optimized background therapy. On day 15, the placebo group began oral lenacapavir plus an optimized background therapy for one week, then switched to subcutaneous lenacapavir once every six months.[3]

The primary efficacy endpoint was the percentage of patients that had a decrease in the HIV-1 viral load of at least 0.5log10 copies/ml by day 15. In the lenacapavir group, that endpoint was seen in 88% of the patients while in only 17% of the placebo group.[4]  In Cohort 2, 36 subjects were given an optimized background regimen on day 1 along with oral lenacapavir on days 1,2, and 8, switching to subcutaneous lenacapavir once every six months (26 weeks) starting on day 15.

A secondary efficacy endpoint involved viral load. The endpoint was a viral load of less than 50 copies per/ml or a viral load of less than 200 copies per/ml. In cohort 1, at 26 weeks, a viral load of 50 copies per/ml was seen in 81% (29 of 36), and a viral load of less than 200 copies was seen in 89% (32 of 36).[4]  In cohort 2, less than 50 copies per/ml was observed in 83% (30 of 36); and less than 200 copies in 86% (31 of 36).[4] The recent report in Lancet: HIV reports data at the 52-week point. At week 52, 83% (30 of 36) subjects in cohort 1 had HIV-1 RNA of less than 50 copies per mL, and 86% (31 of 36 ) had HIV-1 RNA of less than 200 copies per mL.[3] For cohort 2 at 52 weeks, 72% (26 of 36) had less than 50 copies per/ml, and 78% (28 of 36) had less than 200 copies per/ml.

Photo Source: European AIDS Treatment Group

The overall theme is that the results at 52 weeks support the efficacy of lenacapavir injections every six months for those with multi-drug resistance to retrovirals. Consistent viral suppression was met, and therapeutic drug levels were maintained in the blood between injections. Most importantly, since lenacapavir is to be used with other medications, the injections do not increase pill burden or complicate daily regimens. 

Although the results are promising, there are reasons to research much further before expanding lenacapavir for other uses, such as prevention. The cohort size was very small, at 72 participants. That is partly due to the requirements of the subjects. The participants had to have documented resistance to at least two drugs from at least three of the four major antiretroviral classes in addition to having advanced HIV disease. Additionally, while the data showed no significant safety issues, people living with HIV are known to have hypersensitivity issues with drug reactions. The CAPELLA clinical trial, along with CALIBRATE, a different lenacapavir clinical trial, together only have a total of 229 subjects.[5]

Much larger cohorts need to be examined in order to have comprehensive cross-sectional data to explore gender, age, and ethnicity differences. The complex variances of combination antiviral regimens of multi-drug resistant patients are also a significant concern. Once further lenacapavir research is conducted, the path of its utilization will be more apparent. It could even possibly become paired with another complete long-acting drug, creating an easy-to-use twice-yearly injection for all patients, whether multi-drug resistant or not.[5]

[1] Rivera, Viviana. (2023, September 1). FDA approves treatment for multi-drug resistant HIV. Retrieved from https://medicalxpress.com/news/2023-09-fda-treatment-multi-drug-resistant-hiv.html

[2] FDA Press Release (2022, December 22). FDA Approves New HIV Drug for Adults with Limited Treatment Options. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-drug-adults-limited-treatment-options

[3] Ogbuagu, O., Segal-Maurer, S., Ratanasuwan, W., Avihingsanon, A., Brinson, C., Workowski, K. A., Antinori, A., Yazdanpanah, Y., Trottier, B., Wang, H., Margot, N., Dvory-Sobol, H., Rhee, M. S., Baeten, J. M., Molina, J., DeJesus, E., Richmond, G., Berhe, M., Ruane, P., . . . Rassool, M. (2023). Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial. The Lancet HIV, 10(8), e497–e505. https://doi.org/10.1016/s2352-3018(23)00113-3

[4] Segal-Maurer, S., DeJesus, E., Stellbrink, H., Castagna, A., Richmond, G., Sinclair, G., Siripassorn, K., Ruane, P., Berhe, M., Wang, H., Margot, N., Dvory-Sobol, H., Hyland, R. H., Brainard, D. M., Rhee, M. S., Baeten, J. M., & Molina, J. (2022). Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. The New England Journal of Medicine, 386(19), 1793–1803. https://doi.org/10.1056/nejmoa2115542

[5] SHarris, M. (2023). Lenacapavir: an attractive option, but proceed with caution. The Lancet HIV, 10(8), e486–e487. https://doi.org/10.1016/s2352-3018(23)00170-4

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.   

Modern Antiretroviral Therapy is Less Toxic, but Not Free from Side Effects

By: Ranier Simons, ADAP Blog Guest Contributor

Antiretroviral therapy (ART) has indisputably improved the medical outcomes of people living with HIV/AIDS (PLWHA). ART increases life expectancy, prevents people with an HIV-positive diagnosis from reaching an AIDS diagnosis, brings many patients back from AIDS into healthier CD4 counts, and even renders many undetectable. Today’s current lines of defense are also increasingly less toxic than earlier drugs. 

Photo Source: 4Life4Me+

AZT, the first antiretroviral (ARV) used alone against HIV, was so toxic that it caused a faster health decline than HIV would have in people left untreated. The side effects, including damage to bone marrow, made people feel worse than they did without it. Although ART has evolved significantly, it is not perfect. Current ARVs have fewer serious or unbearable adverse issues; however, many PLWHA still deal with side effects.

Some side effects are short term lasting only a few days or weeks. Conversely, some can be much more long-term. It is important to remember that the side effects of one medication can vary from person to person in type, severity, and number. Additionally, some drugs take months to years to develop side effects. PLWHA are living longer and thus are on ART for more extended periods. Researchers are concerned about the potential cumulative toxicity that can develop from long-term use.[1] 

Diarrhea, depression, other mood changes, and hypertension are three common side effects of ART.[2] Diarrhea is one of the most prevailing side effects and causes some people to stop taking their medications. Commonly, it is a side effect of protease inhibitors like ritonavir which may damage the intestinal lining.[3] Immodium (loperamide) is a common over-the-counter remedy used to help PLWHA deal with diarrhea. There are frequently prescribed solutions such as Mytesi (Crofelemer) as well. Derived from the red sap of the Croton lechleri plant, it is just the second botanical prescription drug approved by the U.S. Food & Drug Administration (FDA).[2] Unfortunately, while effective, some State AIDS Drug Assistance Program (ADAP) drug formularies do not offer it.

Depression in PLWHA can have many causes. For some, it can be the psychological result of dealing with having the disease. It can also be caused by the penetration of HIV across the blood-brain barrier and infection of the central nervous system.[4] However, it can also be a side effect of some ARVs. In fact, many list depression or strange dreams as a side effect.[4] Efavirenz, which is in drugs like Atripla, is known for causing nightmares, vivid dreams, or depression.[5] While being a comorbidity among PLWH, hypertension is also shown to be a side effect of some ARVs. Studies show that the chronic inflammation associated with HIV and ART is a significant factor in the high prevalence of PLWHA with high blood pressure.[2]

Photo Source: Ivan Toms Centre

A side effect of ART not well-known by many is Diabetes. Some older nucleoside reverse transcriptase inhibitors and older protease inhibitors that are no longer used as much, such as zidovudine and lopinavir, respectively, cause pancreatic damage.[2,6] Newer treatments, such as integrase inhibitors like dolutegravir and bictegravir, have been correlated with weight gain.[6] Unhealthy weight gain increases the risk of developing Diabetes as well. Integrase inhibitors have been shown to lead to faster viral suppression than some other ARVs.[6] Thus, eating well and exercising when using them is essential to mitigate any possible weight gain.

Fortunately, with the breadth of current options available, PLWHA are not stuck dealing with lifestyle challenges or unpleasant and possibly severe side effects to maintain viral suppression. Suffering from adverse effects results in poor medication adherence or complete abandonment. PLWHA are encouraged to communicate with their care team when a medication switch may be necessary. Sometimes PLWHA feel as if too many medications are becoming toxic in their body. In this case, their physician may be able to switch them from a three-drug regimen to a one or two-drug regimen.[7] 

Some ARVs have to be taken with food or even specific types of food. When that becomes a problem, there are options for those who have specific dietary restrictions by choice or necessity. HIV-positive pregnant women must beware of birth defects some ARVs can cause. For them, dolutegravir-based regimens are recommended.[7] PLWHA at risk of kidney problems are directed not to use regimens like Stribild and Truvada, which contain tenofovir disopoxil fumarate (TDF), which can cause them harm.[7] Regimens containing tenofovir alafenamide (TAF), such as Biktarvy or Descovy, better serve that population.[7] Even novel options exist for those who do not wish to take pills. The FDA approved Cabenuva, a two-shot injectable regimen containing rilpivirine and cabotegravir, in 2021. The two injections are administered in a doctor’s office every two months.[7]

All drugs cause side effects, even essential established medications like aspirin. Although newer ARVs don’t have the number or severity of side effects as ones from the past, it is misleading to describe newer regimens as “free from side effects.” Knowledge of possible side effects of regimens enables PLWHA and their doctors to make informed decisions about their care. Moreover, awareness empowers patients to distinguish between side effects and adverse outcomes caused by other issues. Being educated is empowering as well as informs realistic expectations.

[1] Chawla, A., Wang, C., Patton, C., Murray, M., Punekar, Y., de Ruiter, A., & Steinhart, C. (2018). A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population. Infectious diseases and therapy, 7(2), 183–195. https://doi.org/10.1007/s40121-018-0201-6

[2] Yahoo News. (2023, July 3). 2023 Treatment Guide: Dealing With HIV Med Side Effects? Retrieved from https://news.yahoo.com/2023-treatment-guide-dealing-hiv-134944629.html?soc_src=social-sh&soc_trk=tw&tsrc=twtr

[3] MacArthur, R. D., & DuPont, H. L. (2012). Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 55(6), 860–867. https://doi.org/10.1093/cid/cis544

[4] Rapid Response Service. (2009, March). HIV medication and depression. Retrieved from https://www.ohtn.on.ca/rapid-response-hiv-medication-and-depression/

[5] Cairns, G.(2012, October). Efavirenz and the brain: are we nearer to solving a mysterious side-effect?.Retrieved from https://www.aidsmap.com/news/oct-2012/efavirenz-and-brain-are-we-nearer-solving-mysterious-side-effect

[6] Haynes, R. (2021, January).Type 2 diabetes and HIV. Retrieved from https://www.aidsmap.com/about-hiv/type-2-diabetes-and-hiv#:~:text=Some%20anti%2DHIV%20medications%20may,taken%20them%20in%20the%20past

[7] Yahoo News. (2023, June 29). 2023 Treatment Guide: Is it Time to Change Your HIV Regimen? Retrieved from https://www.yahoo.com/entertainment/2023-treatment-guide-time-change-203031820.html?soc_src=social-sh&soc_trk=tw&tsrc=twtr

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.  

Flawed Mifepristone Decision Threatens Public Health

By: Ranier Simons, ADAP Blog Guest Contributor

Ideological attacks on evidence-based established medical science through litigation continue to threaten the healthcare of millions. New legal challenges from anti-abortion groups restricting access to mifepristone join continued pushback from the Braidwood vs. Becerra decisions in the current news cycle. 

In November of 2022, an anti-abortion coalition of doctors called The Alliance for Hippocratic Medicine sued the U.S. Food and Drug Administration (FDA) stating that the agency improperly approved the drug mifepristone in September 2000. The group purports that the drug has serious safety issues that the FDA did not adequately consider. It claims the studies the FDA cites confirming the safety of mifepristone are flawed; thus, the drug should be taken off the market and approval revoked. Additionally, the group claims the FDA approved the drug using an accelerated process that was not thorough, thus abusing its authority.[1] 

Photo Source: Ohio Capital Journal

Mifepristone used in conjunction with misoprostol is the current established method of chemically inducing the termination of a pregnancy. Mifepristone is a steroid that starts the process and misoprostol makes the body expel the pregnancy tissue. Data has proven the duo to be the most effective with the least number of complications. Using misoprostol alone is not as effective and can result in complications that result in the need for surgical intervention to complete the abortion. It is safe to use misprostol alone with 93% of women using it alone having complete abortions without surgical assistance.[2] However, there are currently no official FDA backed protocols for using it alone.

Attorneys from the Alliance Defending Freedom represent the physicians. Alliance Defending Freedom is the same group that worked with Mississippi lawmakers on the suit at the center of the Dobbs v. Jackson Women’s Health Organization decision, which eventually overturned Roe V. Wade.[1] The group made efforts to get the case heard by Judge Matthew Kacsmaryk, of the U.S. Northern District of Texas, a judge Trump appointed in 2019.

The Amarillo division of the Northern District of Texas is a federal district with a single judge, Judge Kacsmaryk. The attorneys knew of his anti-abortion history, which is why they filed in his district. Judge Kacsmaryk has also issued rulings against protections for transgender persons and against asylum seekers forcing a return to Mexico while awaiting processing.[3] Moreover, Judge Kacsmaryk concealed from the Senate Judiciary Committee his authoring of an article titled “The Jurisprudence of the Body,” published in September 2017 in the Texas Review of Law and Politics.[4] In the article, he stated the Obama Administration had ignored the beliefs of religious physicians who “cannot use their scalpels to make female what God created male” and “cannot use their pens to prescribe or dispense abortifacient drugs designed to kill unborn children.”[4]

The case before Judge Kacsmaryk has not gone to trial yet. However, he held a hearing regarding the issue, whose results were released on April 7, 2023. He stated that the Alliance for Hippocratic Medicine had legal standing to sue, and that the FDA’s approval of mifepristone should be suspended nationwide while the case plays out in court. Additionally, he delayed the effective date of his ruling for a week to allow the Biden Administration to appeal.[1] The decision was appealed to the United States Court of Appeals for the Fifth Circuit, which ruled partially against Judge Kacsmaryk on April 12, 2023.

The appeals court ruled that Judge Kacsmaryk could not reverse the FDA’s 2000 approval of mifepristone because the statute of limitations for the plaintiffs to claim harm had passed. However, the three-person appeals panel added restrictions. The restrictions effectively reversed additional approvals for use the FDA issued in 2016 based on ongoing evidence-based research that had developed since its initial approval. The appeals court ruled that mifepristone should only be used up to 7 weeks of pregnancy, down from its current limit of 10 weeks. Additionally, it ruled that the drug could no longer be sent through the mail, it could only be obtained in person via three different doctor visits, and it could only be administered by a qualified physician instead of other medically qualified and licensed caregivers. The appeals court also invalidated the FDA’s 2019 approval of a mifepristone generic made by GenBioPro.

This ruling still greatly restricts mifepristone’s usage. It prevents pharmacies, both in-person and by mail, from dispensing the medication. Shortening the window in which the drug can be used reduces options for women depending on when they discover they are pregnant. The requirement of in-person doctor visits is one of the most significant hindrances. Requiring in-person doctor visits increases patients' costs of paying for multiple doctor visits, whether through insurance copay cost sharing or entirely out of pocket if uninsured. Additionally, it prohibits prescribing the drug through telehealth visits.

Photo Source: WHYY PBS | The Associated Press

In response to the appeal court’s ruling, the U.S. Department of Justice (DOJ) submitted an emergency consideration before the Supreme Court. As a result, on April 14, 2023, U.S. Supreme Court Justice Samuel Alito issued a temporary stay on all the lower court rulings. The temporary stay leaves mifepristone usage unchanged from the status quo until 11:59 PM Wednesday, April 19, 2023.[5] Both sides are instructed to submit responses so that the Supreme Court can ultimately rule if mifepristone can remain unencumbered while the appeal plays out or if the appeal court limits will be reinstated pending court trial.

U.S. Solicitor General Elizabeth Prelogar stated that “the lower court rulings are the first-time judges have repealed the conditions of an FDA drug approval based on a disagreement over the agency’s judgment about safety.”[5] Many pharmaceutical companies, patient advocacy groups, physicians, and government officials have been sounding the alarm concerning the danger of the initial case and its appeal. On April 14, 2023, 253 members of Congress (50 Senators and 203 Representatives) filed an amicus brief asking the Supreme Court to give relief from the district court ruling and the appellate ruling. 

They stated in the brief that “emergency relief from the order is necessary to mitigate the imminent harm facing members of the public, many of whom rely on the availability of mifepristone for reproductive care—and many more of whom rely on the integrity of FDA’s drug approval process for continued access to life-improving and life-saving drugs. Congress intended to—and did—vest authority in FDA to evaluate and ensure the safety and efficacy of drugs in the United States, and Amici call on this Court to give due weight to that intent.”[6]

A group of over 160 CEOs, healthcare organization presidents, and physicians also filed an amicus brief detailing the negative consequences of the ruling from an industry perspective.[7] In the brief, they explain several arguments against Judge Kacsmaryk’s and the appeals court ruling. The central idea is that the judge nor the court has the scientific or medical expertise to challenge the validity of the evidence behind the FDA. Mifepristone has been in use for over 20 years and has been extensively researched. The lower court rulings would also prevent the FDA from effectively using new data that comes from comparative safety data from real-world evidence. As drugs are used, continuous examination results in changes to initial use recommendations. The lower court rulings stifle the FDA’s ability to depart and evolve from a drug’s initial clinical trial findings. 

The legitimacy of the authority of the FDA is what is at stake. Rachel King, BIO's Interim President and CEO, stated: “We’ve repeatedly warned that the District Court’s decision would set a dangerous precedent for undermining the FDA, has consequences that extend well beyond the single drug, and stokes regulatory uncertainty in an industry responsible for bringing life-saving and life-enhancing therapies to vulnerable patient populations.”[8] 

Allowing ideology and special interest agendas to upend medical science threatens public health. It also threatens destabilization of the entire drug development infrastructure and investment. The results of the cases will have ripple effects regardless of the resolution.

[1] Kimball, S., Luhn, M., Mangan, D. (2023, April 7). Federal judge suspends FDA abortion pill approval, gives Biden administration time to appeal. Retrieved from https://www.cnbc.com/2023/04/07/federal-judge-stays-fda-abortion-pill-approval-gives-time-to-appeal.html

[2] University of California San Francisco. (2023, February 26). The recommended protocol for misoprostol-Only abortion. Retrieved from https://www.ansirh.org/research/research/recommended-protocol-misoprostol-only-abortion

[3] Kitchener, C., Marimow, A. (2023, February 25). The Texas judge who could take down the abortion pill. Retrieved from https://www.washingtonpost.com/politics/2023/02/25/texas-judge-abortion-pill-decision/

[4] Kitchener, C., Marimow, A., Barnes, R. (2023, April 15). The controversial article Texas federal judge Matthew Kacsmaryk did not disclose to the Senate. Retrieved from https://www.texastribune.org/2023/04/15/kacsmaryk-law-review-article-washington-post/

[5] Kimball, S. (2023, April 14). Supreme Court lifts abortion pill restrictions for now. Retrieved from https://www.cnbc.com/2023/04/14/supreme-court-temporarily-blocks-abortion-pill-restrictions.html

[6] Murray, P. (2023, April 14). Democrats in Congress File Amicus Brief Urging Supreme Court to Prevent Dangerous Ruling From Restricting Access to Mifepristone Nationwide & Upending FDA Approval Process. Retrieved from https://www.murray.senate.gov/democrats-in-congress-file-amicus-brief-urging-supreme-court-to-prevent-dangerous-ruling-from-restricting-access-to-mifepristone-nationwide-upending-fda-approval-process/[8

[7] Case 23-10362. (2023, April 11). Unopposed motion for leave to file brief of pharmaceutical companies, executives, and investors as amici curiae in support of appellants' motion for stay pending appeal. Retrieved from https://www.bio.org/sites/default/files/2023-04/2023-04-11-amicus-brief.pdf

[8] BIO. (2023, April 11). Press Release: BIO joins amicus brief challenging court's efforts to undermine FDA's authority to bring treatments and cures to patients. Retrieved from https://www.bio.org/press-release/bio-joins-amicus-brief-challenging-courts-efforts-undermine-fdas-authority-bring   

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.