OPDP's First Letter in a Year...

By now you have heard Xeris Pharmaceutical's was the recipient of the first Untitled Warning Letter in over a year and the agency laid it on them (maybe because this was letter two for this organization in three years - I know some REALLY awesome Compliance & Regulatory Strategists, let me know if you want their names!). They made several comments, which Porzio (who has the AHHHHMAZING Alicia Whittlesey on staff) summarized well, so instead of reinventing the wheel, this is from them last week:

?According to OPDP, the “What is Recorlev??” webpage misleadingly overstates the efficacy of Recorlev with claims such as, “67% of patients who moved on to the second part of the study had normal cortisol levels by the end of the study.” OPDP acknowledges that the PI states, 67% of patients in the SONICS study had normal cortisol levels at the end of the titration phase; however, OPDP explains, the titration phase was not the “end of the study,” and the presentation omits material information necessary to interpret the study results from the SONICS study.?Additionally, the claim "More patients who were on a stable and steady dose of Recorlev had normal cortisol levels", according to OPDP, provided a misleading impression regarding the general experience of patients with the drug. The Agency also takes issue with Xeris’ presentation of risk, notably “Side effects can occur with Recorlev, including some that are serious,” indicating Xeris minimizes serious and significant risks of the drug, and does not prominently display the drug’s boxed warning or specific potential side effects, including potentially fatal ones.?

A copy of the Untitled Letter is available?here.

Basically, FDA said "you overstated efficacy, understated safety and risk information (BIG TIME), and misrepresented data to potential patients" and then followed that up with "whip yourself into shape in 15 days or you'll pay".

Now one might ask themselves if warning and untitled letters are common and how bad could it be anyway? Well, let's break it down a bit - since 2020 there have been a total of 17 letters, which is low considering the all time high was 156 in 1998 (yes, that's in a single year), the closest we've seen to that insanity was 52 in 2010 (I missed that by a year, joining pharma in 2011); however, a short 11 years later we are down to 1 letter in 2022. Either we got good at interpreting guidances in industry or the agency was a little lost in trying to wrap their head around the technological advancements that their late 1960's regulations are trying to govern. I think with the rise in modular content and the industry turning their focus to dynamic access of this content to gather as much information as possible, the sheer volume of NPP materials with a data feedback loop similar to personalized promotion is going to go through the roof. Once that happens it will be significantly easier and cheaper for Commercial to create their own market studies and gather lots (and lots and lots) of data for Marketing campaigns, but it also means MLR is going to be inundated with innovative tech-heavy material, which will be submitted into the same process and workflows we've been using for the last 15+ years. We've slapped lipstick on the pig, and she looks darn pretty in that shade of orange ??, but we still have the same issues we've always had. People hate MLR and the only way out is through, so let's sit down cross-functionally to figure out how to collaborate better to CHANGE this process. And please keep in mind it has to be PEOPLE first (do I have the right people in the right positions doing the right things and do they know the right stuff), THEN process (does this support my people to efficiently do what they need to do), and THEN technology (what additional efficiencies can the collective gain).

But I digressed from OPDP letters...two things need to be recognized and remembered from this moment in time. The first is just because you got away with something once does NOT mean you will get away with it forever. And just because I'm like a dog with a bone, I want to drive the point home - you have to remember that the inappropriate activity has a built in self-destruct mode the more you make the same mistake. Meaning, if you have a likelihood of getting caught once in one hundred times the more you do it the higher the risk each subsequent time and eventually you WILL get caught. Don't be that guy. Besides, jail is not fun and no one looks good in stripes or that shade of orange (except the pig??).

The second is if your MLR committee isn't a cohesive team that is fully supported by their leadership then it's time to make a change because committees that don't jive or communicate effectively are committees that let things like this slip through and the company pays. Your MLR committee is your safety net - they mitigate risks that you don't even know exist so use them and, while I'm at it, respect their experience. They're telling you that you cannot do that for a reason, but if you let them finish their sentence instead of interrupting when they take a breath, you will hear your options. MLR Reviewers are trained to come to the table ready to say "that's not possible" and (this coordinating conjunction is IMPORTANT) to provide you options when they do - let them help you. It's not a personal attack and I can promise you 99% of the time they WANT this to go to market it's just the appropriateness that needs to be adjusted to get it there.

If you want to talk more about how to get your committee set up or how to get them to collaborate better through strategy setting, shoot me an email. I specialize in PEOPLE FIRST, THEN process, AND THEN technology - but I promise you get the whole dang thing!