What They Said – FDA Press Releases in 2023

Less is more?

Every so often is it worthwhile to look back at FDA to see what they had to say in a given year, and in addition, how they said it. One might not think that a large agency would vary much in terms of volume or style from year to year, but that is not the case.

How Many? This year the agency issued 190 releases, which is a substantial cutback from recent years in terms of sheer numbers. The last time the agency issued less than 200 releases to the public was back in 2017. There was a marked pickup during that when FDA was overseen by Dr. Scott Gottlieb who introduced frequent releases that were from his office directly, a practice that had prior to that time been very much an exception and not a rule. The peak year, 2020, represents another big increase and coincides with the advent of COVID when there was a great deal to say about the current environment.

As noted in a posting on the half year check up, two factors figure in to the large drop. First, the COVID subject matter has slowed to a trickle. And second, the agency switched last year from issuing separate “FDA in Brief” notices to issuing releases called “FDA Roundup” that covers multiple items that, on their own, might not be press release-worthy in terms of news impact. In fact, the use of FDA Roundups appears to be on the rise, and this might be a factor in fewer traditional press releases coming out of FDA. In any case, no doubt about it, the agency volume of traditional releases has subsided greatly. If you factor out the FDA Roundups from the number for 2023, then the agency only sent out 102 traditional press releases.

What Did They Talk About? While in general, there was less talk, more of it was about approvals, which comes as little surprise perhaps given the fact that the number of new molecular entities (NME) approved by FDA during 2023 numbered 55, compared to only 37 the year before – a big jump and giving FDA much more to crow about. That said, only 25 releases were about the approval of new drugs, indicating that even though an approval may involve an NME, they don’t always issue a press release about it. The number of releases in relation to new gene therapies increased from 3 to 5, however it is worth noting that one of the 2023 releases actually addressed the approval of 2 new gene therapies in one release. Finally, no surprise here, the number of announcements about new vaccine approvals fell as the COVID pandemic entered a new phase.

General Announcements include any releases not categorized in the other categories and also includes FDA Roundups. The communications about legal actions (Consent Decrees, Warnings, Seizures, e.g.) was up while announcements about new rules (Guidances, Regulations and Policy announcements) were nearly flat.

Did They Speak Spanish? The agency is spotty about issuing releases that are both in Spanish and English, but it would appear that this year there were more releases than ever issued in bilingual fashion. New approvals were the category that most often (but not always) in both languages. Overall, when you take out FDA Roundups which are always solely in English, it looks like 71 percent of the time, the agency went bilingual. Last year by my count it was only 55 percent. The number of releases was lower than last year, but the proportion of bilingual has gone up.

So far 2024 has started off very quietly. In January FDA issued only 2 press releases while the balance of communications were handled through a large number of “FDA Roundups”. A single NME was approved in January. Stay tuned to see how it looks in a mid-year assessment.

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FDA’s OPDP Sends First Regulatory Letter of the Year Aimed at Rx Drug Promotion

Last week FDA’s Office of Prescription Drug Promotion issued its first regulatory action letter of the year. This was an Untitled Letter – a/k/a Notice of Violation Letter (NOV) – sent by the agency to Novartis in relation to promotional content regarding the cancer treatment KISQALI(r) (ribociclib). The communications vehicle that was the subject of the letter was a Direct-to-Consumer (DTC) television advertisement that had been submitted for agency review.

Before getting to the specifics of this particular letter, a look at how it stacks up against recent enforcement. Aside from being the first letter of 2024 – after 2023 when there were only 5 enforcement actions – the letter marks the second in a row concerning DTC TV ads, the last one being issued in October 2023. Too few to be a trend perhaps, but with such low levels of enforcement may nevertheless be noteworthy. DTC Ads, after all, do reach a very large audience.

There is a larger trend that may be in play – not the communications vehicle, but regarding the type of violation cited by OPDP. In this case, the most recent letter involved statements in relation to efficacy and the support cited for the making the claim. While the omission or minimization of risk is traditionally the most common violation cited in letters regarding promotional communications, the previous 8 letters issued by OPDP had issues with the presentation of efficacy information, making this the ninth in a row. Coupled with the fact that in 2023 OPDP announced that the office was conducting new research – “A Survey on Quantitative Claims in DTC Prescription Drug Advertising” and December 2023 guidance on “Presenting Quantitative Efficacy and Risk Information in DTC Promotional Labeling and Advertisements” it would be reasonable to assume that the presentation of efficacy claims is a subject getting the particular attention of the agency.

Regarding this particular letter, in addition to the characteristics already mentioned, the claims that were the subject of OPDP action involved expressions regarding quality of life (QoL). Specifically, the agency cited claims that the drug “helps preserve quality of live so that you’re not just living, you’re living well.” The claim was accompanied by a cited reference describing a clinical trial where QoL was included as a secondary endpoint.

FDA took issue with several aspects of this claim. A few of the more interesting ones – (1) the agency said that the cited study design precluded drawing conclusions regarding QoL and that the outcome could have occurred by chance alone. Even though OPDP noted that the ad carried a SUPER on a frame that stated that the analysis was not pre-planned to detect a false positive that it was insufficient to address the potential for creating a misleading impression. The agency said that the data from the study, while hypothesis generating, were not conclusive. (2) Moreover the collection of QoL data, the agency said, did not account for confounding factors that might be present for individuals from non-cancer related factors such as other health problems or personal life-issues. (3) In addition, the agency took exception to the claim that treatment with the medication “helps preserve quality of life so… [patients] are living well” because OPDP said that this presupposes that the patients were living well at the outset of the clinical trial, and (4) A voice over and graphic in the ad claimed that patients would “live longer” which is explained further in a SUPER, but the agency found that this presentation was in competition with distractions that undermined audience understanding of overall survival, with the agency citing data on audience reading comprehension. The agency found the expression of claims was out of balance with the qualifiers to those claims. A thorough reading of the letter will yield further insights into the OPDP perspective and will give a more fully rounded and detailed understanding of the agency’s thinking in this regard.

In sum, this Untitled Letter signals not only a continued interest in the subject of how companies express efficacy data in promotions generally, but specifically sheds a light on the guard rails the agency has in mind relating to claims regarding quality of life.

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The Year in AdComms – A Look Back at 2023

For those working closely with the development of new medicines for FDA approval, it can be informative respecting the future to look back at recent activity and take note of any potential changes from years past. Now, with no more AdComms scheduled for 2023 – and it being highly unlikely that any will be – it is that time of year to do just that. What we find is that it was somewhat of a milestone year in terms of volume, outcomes and style.

Virtual Meetings. Let’s start with the obvious. We are still in virtual meeting territory. At the outset of the COVID-19 pandemic, FDA began conducting advisory committee meetings virtually. Prior they had been held in-person on the FDA campus (and prior to that, in hotels around the Washington, D.C. area). The quality of the virtual meetings has gotten better over time, though there are still occasional technical issues that impact the quality of the proceedings. Lost also are the many collateral benefits to in-person meetings where there is an ability to network among attendees and media, among other things. While 2023 maintained virtual meetings, it is perhaps noteworthy that FDA has scheduled an in-person advisory committee meeting of the General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee to be held February 6, 2024. Does this signal a return in 2024 to in-person meetings? In response to outreach, the media office only would state that that “[i]n person and hybrid meetings will continue and will depend on the particular meeting and committee.”

Volume of Meetings and Outcomes. During 2023, there were a total of 29 FDA Advisory Committee meetings related to human drugs, 25 of which were held to discuss either the approval of new drugs or the approval status of medicines approved under the accelerated approval pathway. Of those 25 AdComms, votes were held during 23 meetings, 18 of which had votes recommending approval and 5 of which did not. There were two examples of meetings where advisory committees recommended approval, but ultimately the agency did not approve – and there were no circumstances this year where the agency approved in spite of a lack of such recommendation from a committee.

There are two things of note from this year. First, there was an increase in the number of meetings held to consider the status of new medicines, the most since 2018 and far more than were held in 2020, 2021 and 2022. Secondly, the meeting outcomes were much more positive than they were in those same years. In fact, in 2021 and 2022 more drug applications resulted in negative recommendations than positive ones – with the number of negative outcomes in 2022 being more than twice positive recommendations. By contrast, in 2023, the number of recommendations for approval was over three times the number of negative outcomes. Both in terms of volume and outcomes, the needle has moved considerably.

Committees with the Most Action. No surprise – the committee that met the most times was the Oncologic Drugs Advisory Committee, with six meetings during 2023. The Antimicrobial and the Cellular, Tissue, and Gene Therapy each met three times. Those that met twice included the Anesthetic, Endocrinologic, Peripheral and CNS and Pulmonary committees. Those that met only once included the Cardiovascular, Gastrointestinal, Obstetrics and Psychopharmacologic.

About Voting. Much was made earlier in the year when FDA Commissioner Robert Califf stated that he hoped to see more discussion and less voting during advisory committee meetings. Last year, FDA experienced a great deal of public attention on the fact that the agency approved a treatment for Alzheimer’s after a lopsided negative vote from the advisory committee meeting on the matter. At the same time, the head of the Oncology Division at FDA was quoted in media as saying that the role of voting was very important. Things do not change quickly at FDA as a rule, and this year we did see two advisory committee meetings where there was no voting question posed to the committee. The first was a meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee meeting to discuss an investigational treatment for Sickle Cell Disease, and the other was a meeting of the Oncologic Drugs Advisory Committee which was convened to discuss updates on the accelerated approval status of two new drug applications previously approved under the accelerated approval pathway. We will have to look to 2024 to assess whether there is any meaningful change in FDA policy in regard to voting.

Committee Vacancies. A survey of the rosters of all of the human drugs advisory committees shows that the agency is ending the year with a large number of vacancies with 16 of the 17 committees with vacancies. In total among all the committees, there are 56 vacancies.

Things to look for in 2024. (1) Voting questions for meetings considering NDA approvals; (2) getting these many vacancies filled; (3) whether or not there will be in-person meetings to put that meeting room to use again; (4) whether the number of meetings will hold steady and (5) will outcomes continue to be so positive for new drugs?

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FDA’s OPDP Issues Two New Untitled Letters

While enforcement has been at a low ebb for quite some time with FDA’s Office of Prescription Drug Promotion (OPDP), this week took a different turn with the posting of two new untitled letters sent October 31. That brings the total number of letters issued by OPDP to five this year – one Warning Letter that came out in August respecting a sales aid used in promoting a treatment for COPD, and 4 untitled letters – one in June, one in August, and now two in October.

The first letter posted this week was issued on October 31 and was in sole relation to a direct-to-consumer brochure that contained promotional claims for an on demand contraceptive. In it, language was used to assign a specific percentage in relation to the product’s efficacy. FDA said that the use of this specific statistic was misleading in that it did not use a validated methodology and did not agree with the means used to describe efficacy in the PI for the product.

Likewise, the second letter posted this week, also issued on October 31, involved two different communications vehicles – a DTC broadcast advertisement and a banner ad that contained promotional language regarding an adjunct therapy for major depressive disorder – but focused on the same issue as the previous letter in relation to the promotional issue that concerned OPDP. Here again, OPDP compared the statistic used to describe efficacy with that of the PI for the product and found a difference between the two, resulting in the issuance of the untitled letter.

Looking for trends in recent enforcement, one does not see any pattern in terms of the types of communications vehicles – 2023 involved a Website, a sales aid, two banner ads, a brochure, and a DTC broadcast advertisement. And while contraceptives were involved in two of the 2023 enforcement actions, it seemed more like a coincidence than an area of concentration on the part of the agency. And they were pretty evenly divided between digital and traditional communications vehicles. There was no concentration among products with boxed warnings.

But there has been one trend worth noting. In fact, looking back to enforcement beyond this year through March of 2022, one can see that the last 7 letters issued by OPDP to pharmaceutical companies about promotional communications all involved a tie between a particular efficacy claim and the data from which it was derived, or where an efficacy claim appeared unsupported by data. So there is perhaps a message worth paying attention to here. The trend would indicate extra caution may be prudent when pharmaceutical and biotech companies are assigning specific performance percentages to their promotional claims when being derived from sources other than the PI for the product.

This leaves us with a total of five letters this year, more than last year, and less than the year before. In a period of such low enforcement it is difficult to discern a trend. But we still have several weeks left to the year, and in 2016, OPDP issued several letters in December to boost the total for that year into double digits. We’ll have to wait and see for 2023.

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FDA Launching New Advisory Committee on Digital Health

FDA announced this week the formation of a new advisory committee – the Digital Health Advisory Committee – for the purpose of providing the agency with advice on matters related to digital health technologies (DHT). FDA does not form new advisory committees all that often, making it a notable development in more than one respect.

FDA stated in the agency’s press release that the committee’s subject matter jurisdiction will include helping the agency explore and assess issues regarding artificial intelligence/machine learning (AI/ML), augmented reality, virtual reality, digital therapeutics, wearables, remote patient monitoring and software. That is a broad spectrum of subject matter. The AI/ML portion alone is growing rapidly in breadth as is its uptake.

Simultaneous to the announcement, the agency began recruiting for its membership for the nine members the agency is seeking to comprise the membership of this committee. By design there are currently none voting members – which includes the Chairperson – comprising the committee. FDA is looking for a consumer organization to fill a voting slot and nominations and self-nominations will be considered by the agency to fill both consumer and individual seats. According to the Federal Register notice, individuals should be “full-time employees of firms that manufacture medical device products, or consulting firms that represent manufacturers or have similar appropriate ties to industry.”

The agency provided examples of areas where the Commissioner may seek advice which included real world data and evidence, patient generated health data, personalized medicine and use of DHTs in clinical trials to name a few. Right now it is a stand-alone committee subject matter area, not housed under Human Drugs Advisory Committees or Medical Devices. Given the speed and span with which AI/ML is developing, it is easy to think that there will be a basis for future expansion and just as Medical Devices is sub-divided into panels by subject matter jurisdiction, one could imagine the future of the new committee taking on a similar structure given the prolific nature of DHT.

Troy Tazbaz, director of FDA’s Digital Health Center of Excellence stated in the FDA press release – “Many of these technologies are novel and tend to rapidly change; it’s our duty to seek as much knowledge on them as possible as we determine and implement appropriate regulation to encourage innovation while protecting the public health.” This is one to keep an eye on for sure – not only to see what subject matter comes before the committee, but how rapidly it grows.

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