Replies to post #54409 on Biotech Values

[zipjet]

>>One of the first analysts to ask questions on the conference call said something along the lines of:
"This is like a 'When did you stop beating your wife?' question. How do you know that your generic product is no more immunogenetic than the branded product when there is no data on what is normal for the branded product?"

The point was well taken. It is even more potent when you know that there is substantial batch to batch variation between Lovenox batches. Which batch do you compare to?

I thought anther interesting take-away from the CC was that there is no "approvable letter" issued in ANDA's. So while the FDA response is in the form of a "not approvable letter" the requests for additional information on immunogenicity is similar to requests received in "approvable letters". As we know approvable letters vary in difficulty from easily produced info to doing more human studies.

ij

[DewDiligence]

>It would be interesting if immunogenicity data will have to be collected for all potential generic drugs submitted via an ANDA.<

I assume you mean generic drugs that are complex mixtures, as Lovenox is. It would hardly make sense for the FDA to ask for immunogenicity data in a typical ANDA. (Nor does the OGD section of the FDA need an excuse to increase its workload!)

>wow, MNTA first filed the ANDA in August of 2005, and this is the first time the FDA mentioned immunogenicity?<

Teva and Amphastar field their generic-Lovenox ANDA’s in 2003.

>…does it always take this long for generics to be reviewed?<

No.

[dewophile]

MNTA

The complexity of the product seems to be at issue here. MNTA has some proprietary method of depolymerizing native heparin, and there is concern that the end result is not quite identical to the approved branded product - no matter how well they have characterized it using their proprietary carbohydrate analytic methods. Much like the FOB conundrum, where companies argue minor changes in conditions and cell lines can alter the characteristics of the final product, here the batch to batch variability and complex mixture of isoforms of the original product make comparisons between the 2 versions far more difficult than a traditional synthetic chemical drug, and may require in the end a bit more than just bioequivalency for approval

that the FDA took so long both to review the application and give guidance is disgusting..but I would argue if MNTA was altering the native heparin backbone in a unique way - knowing that carbohydrates can, albeit rarely, alter immunogenicity - they might have seen this coming, no matter how good their technology was at assessing "similarity" between their product and branded LMW heparin

the good news is that if immunogenicity is the only issue at hand, this shouldn't be too difficult (or take too long) to tease out - and I highly doubt it will ultimately prove to be of any clinical consequence, so why it sold off to the degree it did based on just this is curious