"Clinically superior" and "same drug" are concepts that are important for whether a second to market mesenchymal stem cell product sponsor for the treatment of graft versus host disease can receive an exclusive access to an indication or whether the second player to market is effectively held out.
In other threads on this CYP part of the HC message board some good (relevant but not necessary conclusive) reference material has been provided (by a poster (see post numbers 59585644 and 59587257 I'm not fond of to say the least because of how he behaves on forum) almost in passing.
That poster provided this link https://www.govinfo.gov/content/pkg/FR-2013-06-12/pdf/2013-13930.pdf - which is a Federal Register entry of 12 June 2013 concerning Orphan Drug Regulations (at that time).
Because 2013 is some time ago, as I was reading, I was wondering is it still current. The FDA website which has been updated as recently as 2021 still has a link to the same document - so it seems the FDA itself is still endorsing it as relevant.
To get current definitions of "clinically superior" and "same drug" though I went to these sources (urls) in these images.
I'm going to retype the words because it will make it easier for me to read without being logged in to HotCopper. Also except for Clinically superior where bolding is in the original bolding is mine.
316.3 Definitions
"(3)
Clinically superior means that a drug is shown to provide a significant therapeutic advantage over and above that provided by an approved drug (that is otherwise the same drug) in one or more of the following ways :
(i)
Greater effectiveness than an approved drug (as assessed by effect on a clinically meaningful endpoint in adequate and well controlled clinical trials). generally, this would represent the same kind of evidence needed to support a comparative effectiveness claim for two different drugs; in most cases, direct comparative clinical trials would be necessary; or
(ii)
Greater safety in a substantial portion of the target populations, for example by the elimination of an ingredient or contaminant that is associated with relatively frequent adverse effects. In some cases, direct comparative clinical trials will be necessary, or
(iii) In unusual cases where neither greater safety nor greater effectiveness has been shown, a demonstration that the drug otherwise makes
a major contribution to patient care.
As the other poster has also noted 'sameness' has been something that the FDA have been updating their guidances over and comments are still open to have input to "Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations" - however, in my opinion that document isn't helpful for considering Remestemcel-L (or Ryoncil) vs CYP-001 because these will be cell based drugs but not gene therapies and as that document says in the intro "This guidance focuses specifically on factors that FDA generally intends to consider when determining sameness for gene therapy products and does not address sameness determinations for other types of products". So doesn't address cell-therapy products that are not also gene therapy products.
So it seems to me the best most up to date authority on sameness in considering whether Remestemcel-L and CYP-001 would be the same is in the wording above on "Same drug" and it is poor fitting wording but it is what it is.
Again, so I can read the text offline -I'm typing out the text
"14
Same drug means:
(i) If it is a drug composed of small molecules --- (well neither Remestemcel-L or CYP-001 would be).
(ii) If it is a drug composed of large molecules (macromolecules), a drug that contains the same principle molecular structural features (but not necessarily all of the same structural features) and is intended for the same use as a previously approved drug, except that, if the subsequent drug can be shown to be clinically superior, it will not be considered to be the same drug. This criterion will be applied as follows to different kinds of macromolecules:
(A) Two protein drugs.. " (not relevant)
(B) Two polysaccharide drugs .. " (not relevant)
(C) Two polynucleotide drugs.." (not relevant)
(D)
Closely related, complex, partly definable drugs with similar therapeutic intent (..) would be considered the same unless the subsequent drug was shown to be clinically superior. "
In my opinion mesenchymal stromal cells from either the MSB or CYP process will be able to be described under D in that they are both mesenchymal stromal cells (essentially in their function - with no genetic enhancement having been done to either), they will both be partly defined (because every possible interaction of either product with every patient won't have been explored but trials will have shown both to be safe to a statistical level).
So, if MSB get approval for Remestemcel-L first, a demonstration of clinical superiority will be necessary for CYP's drug to be deemed another drug and to so avoid not being prevented from accessing a market MSB gets an exclusive on.
And clinical superiority is about (a) greater effectiveness, (b) greater safety or (c) a "
major" contribution to patient care.
Personally, I am open to the possibility that CYP might be able to meet the standard of clinical superiority but I also have a strong impression that Ross exaggerates the differences between CYP and what he sort of characterises as earlier conventional methods into which group he bundles MSB so I'm not taking his word for it I'll want to see evidence.
And anyone can find evidence in well sources science if it is there to be found. So this is where I am wanting to here CYPers argue for or point at
evidence of clinical superiority (or to acknowledge that there is no such evidence) and to be aware that if they are quoting Ross that they need to have a basis not just his spruiking. Please.
By the way - cheaper is not a possible category of clinical superiority sufficient to make a drug not be the same as another drug. Cost of goods doesn't cut it.
(20min delay)