Arog Pharmaceuticals Untitled Letter

In a letter dated 6/29, OPDP told Arog Pharmaceuticals that they had been promoting their unapproved drug Crenolanib.

The crux of this letter was that it was OPDP's opinion that Arog was making conclusionary statements about Crenolanib although it had not yet been approved.

This type of letter has been sent out many times over the years by OPDP to companies for pre-approval promotion of drugs.   Looking back over past letters the theme is generally the same:

• Companies fail to make it clear that the drug is investigational and not approved
• Companies make conclusionary statements about aspects of the drug where no conclusion can yet be reached because the drug is not approved
• Companies give or imply an indication for a drug that has not yet been approved.  Obviously this is problematic to OPDP as in many cases there are limitations to an indication once approved.
• Use of words like novel or unique or other words that imply superiority
• In a couple of old examples, indicating lack of adverse reactions with the drug

In the current letter OPDP also cited Arog for indicating that their drug was useable with some forms of full dose chemotherapy.

In many of the letters and supposed promo materials sent out to OPDP, the supposed violations come down simply to choice of phrase.  It is impossible to know from the letters whether the company cited has chosen their words purposely, have just quoted words directly from discussion sections of scientific publications or, more simply, just believed so much in their product and were so unaware of the ad/promo regulations and previous OPDP letters on the subject that they didn't realize that what they were saying or doing was pre-approval promotion.

As I said, it is usually all in the language used.  In many cases just the addition, removal or substitution of a few words changes a claim to a statement of current belief (based on scientific data) about an unapproved drug.  Let's look at the language that was cited and see what could have been said (additions in bold, removed text in cross out):

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o Combination Therapy—Future of A New Hope for AML Treatment 

     o CRENOLANIB - currently in clinical trials  

            o Also being investigated to see if it is combinable with chemotherapy at full doses

o The Goal: Eradicating Activating Mutations  

     o The Hope: CRENOLANIB  

          o Pre-clinical study results suggest that it could be a potent inhibitor of  

                o FLT3   

                o PDGFRα   

                o PDGFRβ 

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o  Crenolanib - A next-gen  new type of tyrosine kinase inhibitor for use being investigated for use in the treatment of FLT3-mutated AML. 

o Pre-clinical data suggests that Crenolanib, a type I TKI, is could be a potent inhibitor for FLT3-ITD and secondary KD mutants

THERE ARE SEVERAL ATTRIBUTES THAT HAVE BEEN DESIGNED IN TO THIS MOLECULE TO HELP SET CRENOLANIB APART FROM OTHER THERAPEUTIC OPTIONS 

1. In clinical studies Crenolanib, whether delivered by itself or as part of a drug combination, has shown showed benefit in FLT3 mutant AML. 

2. There is some evidence that patients who progress after treatment with prior TKIs may still remain sensitive to crenolanib. 

3. Evidence suggests that Crenolanib has favorable pharmacokinetics and does not appear to accumulate with repeated dosing. 

4. Crenolanib is was designed to be a selective type I TKI that does not inhibit wild-type cKIT.

Now, I am not saying that this language would be acceptable to OPDP as the language I suggest is not exactly scientific exchange and I haven't even read the science to see how definitive the results are, let alone know if FDA would think those results were definitive.  However, the changes I suggest would at least address most of the concerns OPDP presented in this most recent letter.  If we are to take the language in this letter as a signal from OPDP as to what would be acceptable to say about a drug that has not yet been approved but for which substantial data was available, then the message appears clear to me: Make clear the drug isn't approved and don't represent statements about the drug as fact when the validity of those statements will be dependent on the outcome of the review of the drug application by FDA and the resultant language in the approved full prescribing information.