The FDA makes a clear rejection of Nonfamilial Hypercholesterolemia

“Familial” means “inherited.” “Nonfamilial” means “uninherited.”

  • The FDA clearly rejected the inclusion of the Nonfamilial disease during the approval process. With this rejection, pharma had essentially asked, “Does it matter if drug candidates actually carry a mutation or is high cholesterol enough?”
  • And the answer was more or less, “Yes it matters if they carry a mutation, and no, high cholesterol is not enough.”
Repatha FDA Approval

It follows by rational argument.

  1.  Pharma explicitly asked for both the Familial and Nonfamilial indication.
  2.  The FDA responds, No, only Familial. Nonfamilial is rejectedfrom the proposed indication.  So this is after a direct consideration.[1]

OmedaRx, a national pharmacy benefit manager, says that Nonfamilial is to be considered “not medically necessary.”[2]

Position statement for alirocumab

Unfamiliar terms give a margin for misunderstanding which common sense would never allow. 

The outline of the FDA-Pharma dialogue is something like this:

  1. Can I give this benefit to both the mutation and non-mutation carriers?
  2. No, it’s not just a benefit; it is also a risk. The non-mutation carriers would be put at unnecessary risk because it appears that other options are available. The mutation carriers appear to have very few options. Therefore, you can give the benefit along with that risk to the mutation carriers, but we do not want to put the non-mutation carriers at risk unnecessarily.

However, the industry has skipped over this rationale. What they have been told not to do is synonymous with what they say they are doing.

Definitions and Logic behind FDA approval for repatha
Logic behind FDA approval for repatha

The medical community is in a state of contradiction. Clear thinking precludes clinical scoring systems.

Contradiction and Off-label Marketing

 “A study on 643 Danish probands could not even find a single phenotypic characteristic to predict the existence of a mutation.” [3]

  1. If the set {FH and Non-FH} is requested,
  2. And if Non-FH is rejected,
  3. Then the set {FH and Non-FH} is rejected.
  4. Consistent with clear thinking, all subsets within {FH and Non-FH} which include at least some Non-FH are also rejected.
  5. Both passing clinical scores and phenotypic FH, as if sufficient, represent the set {some of the FH and large numbers of Non-FH}.
  6. Therefore, both passing clinical scores and phenotypic FH, as if sufficient, are rejected.
  7. If the FDA accepts clinical FH scoring systems that guarantee large percentages of Non-FH, they contradict their rejection of the requested set, {FH and Non-FH}.
  8. If the FDA rejects the set {FH and Non-FH}, then they reject the results of clinical scoring systems.
  9. Thus, the results of clinical scoring systems are off-label.
  10. The promotion of clinical scoring systems is the promotion of off-label drug sales.
  11. The deceptive conflation of Non-FH with FH and the proposal of lower diagnostic standards aggravates the violation of off-label promotion.

[1] https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125522Orig1s000SumR.pdf

[2] https://www.omedarx.com/files/Praluent%2C%20alirocumab%20dru406.pdf

[3] Familial Hypercholesterolemia: The Lipids or the Genes? Akl C Fahed and Georges M Nemer; 2011