In my last posting, I provided an overview from my database of Warning and Untitled (NOV) letters data base that spans the years 2004 – present regarding FDA actions around communications perceived by the agency to be promoting an investigational compound prior to approval. In that posting, we looked at the number of letters, the type, the communications vehicles involved, among other things. Today, we are going to look at the language.
There were 8 letters in all where one can discern how characterizing a compound that is still being investigated with conclusions as to safety or efficacy can catch the eye of regulators:
- November 2008 – An investigational oncology related compound discussed on a Web site. The language used said that the drug “is a biological product designed to…” “is the only drug that can remove…”. In addition, it stated that the drug “contains a recombinant enzyme which rapidly cleaves…” and “was able to achieve a clinically important reduction” – “consistently reduced … concentrations” and said that the drug “is well-tolerated” “a unique drug that allows clinicians to control patient exposure…” (Partial list from the letter)
- January 2011. A cosmetic treatment under consideration for approval discussed in media interviews by a clinical investigator. Statements cited by the agency included one that the drug “will likely come out later this year. Early data shows that it may last longer and kick in faster….” and “I can’t wait to use” the drug. “Effects last a month longer” than the competitive drug on the market; and “It’s time we have something that lasts a little bit longer…” For this letter – there was also consideration of the fact that there were no head to head trials comparing the investigational compound to any other drug out on the market.
- April 2011. Brochure for an investigational oncology compound distributed a conference. Brochure title included the words “new therapies” and described the mode of action saying that it “is particularly active against a number of short-lived proteins…” noting also that as positive data from clinical trials has become known demand for access under compassionate use had increased. Stated that the investigational drug “is a valuable option for the treatment of patients… FDA said that the totality of these claims suggest that the drug is safe and effective for patients.
- June 2011. An investigational oncology compound Web site. Here the site made statements such as that the product “has demonstrated both safety and clinical efficacy….” and that it had a “safety profile that is distinctly different” and that the it was demonstrated in the trials that it “can be safety given to humans” and “has generally been well tolerated. Even when accompanied by specific language stating that “[t]his investigational drug product has not been approved by the US Food and Drug Administration for safety and effectiveness” the agency felt was insufficient to overcome the impression that was given by the language used on the Web site.
- August 2011. An oncology related investigational product set of Web pages. Used language such as saying the product “is non-toxic because it works with the body’s immune system” and “is the first combination immunotherapy” and that it “is able to directly affect both the tumor cells themselves and activate a robust anti-tumor immune response” and “has been shown to be safe and well tolerated”. It also showed some before and after pictures which demonstrated dramatic improvement. There was additional language, but along the same lines as that already stated.
- October 2012. While the primary communications vehicle here is a Web site, the site included press releases and embedded videos regarding an investigational drug in oncology which contained the language that concerned FDA. The release stated that the product was “well-tolerated with easy manageable side effects….” which “compared favorably to radiation therapy and chemotherapy” and citing remarkable response of one patient in the trial. In another press release, the mechanism of action was described and in yet another, similar language to the first that stated that the product was “well tolerated, with just two cases of serious reversible toxicities”. The letter then addresses some language on the Web page that provides specific information on how the compound works and lastly cites a video on the Web site that was entitled “Tomorrow’s Cancer Treatment Today” and talks further about the mechanism of action. This provides an example of how the agency looks at the totality involved in the communication.
- November 2012. This involved discussion of an investigational treatment for diarrhea contained in a podcast on a website. Here there were some statements on the mechanism and what it does and does not do and statements that the product “is ideally suited to treat” the diarrhea and that the product “targets the primary cause”. Further cited was language that stated that the “mechanism of action and safety profile provide a strong rationale for treatment…” and in the podcast there were further statements about what the treatment did – such as the statement that the “product has so many different indications becasue the mechanism of action is a basic normalizing…. so it works for the most severe, acute, infectious…”
- April 2013. Another investigational oncology drug discussed on a website. Statements that the compound “achieves the required therapeutic concentration necessary…” and “demonstrated no significant or lasting side effects in the clinical setting, and had a very favorable adverse event profile”.