from YMB
CC
by: chatalinda 02/23/06 10:27 am
Msg: 28433 of 28454
Interesting CC.
Filtration
The additional filtration process was installed at the request of European regulators. The same regulators now say that said that the submitted data was based on Atryn produced BEFORE the new filter was installed and that therefore the new filter is cited as a concern. This is nonsense because there is no evidence to suggest that Atryn (used in trials) was in any way "contaminated."
Immunology
In over 200 patients, there is no evidence of any antibodies or hyper-reaction to Atryn or to possible impurities. European regulators know this but said since they excluded pregnant women from their review, they now indicate that there is not enough evidence (patients) to show no anti-body formation or no hyper-sensitivity.
Pregnant patients at childbirth
The normal AT level is about 80-120. A lack of it can cause women to die in child birth from bleeding. In child birth, AT-defficient women' AT levels may range from 30-50. These women were given AT to increase their levels, and then blood samples were drawn to verify they had been bought up to/near normal levels. The problem is that there is not a consensus protocol as to WHEN to inject AT or take blood samples, and hence these women were excluded from the final review process. In fact, GTCB studies have gone a long way in creating a useful protocol, thereby filling an important gap in medical treatment. Also, there can be no doubt from available data, the injected Atryn did bring AT levels In AT-defficient women in childbirth) into the normal range, but since there are no consensual criteria as to when (confirmatory) blood samples can/should be taken, the regulators simply excluded the (positive) results for pregnant woman though they are the group probably most in need of AT.
Appeal
GTCB now plans an appeal. I think the filtration issue can be resolved. The harder issue will be to re-include pregnant women -- or more time-consuming testing will be necessary. But GTCB has developed and refined a protocol of injections/testing to maximize and stabilize AT levels in child-birth. But, again, if European regulators are willing to toss out data where the efficacy of AT is so clearly demonstrated for a lack of a consensus protocol (which they were always aware of), there will be dilution (and time) to redo studies using a pre-approved protocol for pregnant women at child birth.
Summary
Immunological issues are a result of regulators' narrow focus, not evidence. The extra purification process was done at EMEA's request. And GTCB is ahead of the game in offering a protocol for women at child-birth. Hence the price bounce during and after the CC. The next 2-3 months will be critical in learning how long it will take GTCB to overcome these last hurdles.
The issues are not efficacy or purity or production of Atryn, but regulatory. There are no doubts about Atryn or GTCB's ability to produce it. The big remaining issue/hurdle is for regulators to define testing protocols for women in childbirth. GTCB may already have that answer in hand.