Design Details of Bapineuzumab (aab-001) Phase III
excerpts from the 3q CC follow (see link in i-Box for full transcript)
Design Introduction: (Lars Ekman)
"Characteristics of the Phase III trial design include the following:
Four (4) separate pivotal placebo control studies with a total of approximately 4,000 patients will be implemented across two sub-populations with mild to moderate Alzheimer's disease. Specifically, there will be two global trials in APOE carriers and there will be two global trials in APOE non-carriers. These trials will be of 18 months duration. We will have a single dose in APOE carriers and we will compare it with the same dose and multiple higher doses in APOE non-carriers. Our objective is to dose the first patient in North America by the end of this year.
In conclusion, we and Wyeth believe that this Phase III program optimizes our opportunity to develop a drug that would slow cognitive and functional deterioration in Alzheimer patients".
Question & Answer:
Corey Davis - Natixis Bleichroeder
"can we conclude that APOE patients are better responders to the drug or that they are more sensitive to vasogenic edema?"
Lars Ekman
"Vasogenic edema is, as I've said many times before, it's a largely asymptomatic and transient MRI finding. We have learned that it is more abundant for carriers. That has influenced the design of the trial, so that we can minimize this event. We do not know yet if that is sort of an adverse event or if it's an event that we're actually striving for, but we have at this point said let's try to minimize that event, and therefore we would only do one dose in those patients. In the APOE non-carriers, we will do the same dose, and then further doses. Some 60% of the Alzheimer patients are non-carriers and 40% are carriers."
"However, I would also like to remind all of us that we have the objective to develop a drug that fits all patients. The ability to use pharmacogenomics to identify specific patients groups is there to optimize the value of the drug and to optimize and find what therapy is best for patients with different genotypes within the Alzheimer disease as a whole. This is to my knowledge one of the first times where in a study of this magnitude companies have prospectively defined specific genotypes in order to optimize the therapy"
Corey Davis - Natixis Bleichroeder
"Okay. And can we assume that there is placebo arm in each of those four studies?"
Lars Ekman
"Absolutely. In each of the four studies there is very well defined placebo group. And in each of the trial is a pivotal standalone trial by itself."
Bill Tanner - Leerink Swann
"I think you did mention that the FDA had looked at the Phase 2 data..... whether you are focused on or just the whole data in general?"
Lars Ekman
"I cannot provide any color on that. As you know, the trial is ongoing and giving you color on that would sort of un-blind the trial. They have seen all the data relating to safety of the drug, related to the efficacy of the drug, so we have shared all the data from this, from that trial, for the Phase 1 trial and based on the totality of that and our experience was in an-1792, we have defined the trial and we have agreed with the trial design with the FDA."
Bill Tanner - Leerink Swann
"on the dosing, I understand the APOE carrier versus non-carrier, sort of understand the rest now, but was the dosing then really arrived at more or the differential dosing arrived at more from a safety perspective trying to avoid the vasogenic edema, I mean I am guessing what is known then about the relative efficacy Bapineuzumab and the two different types of patients?"
Lars Ekman
"We have not disclosed any efficacy in these two genotypes, that's obviously when it comes to that, it will fall out, as we know the totality of the data and it would then be disclosed. And we know that there is an abundance of vasogenic edema in the APOE e4 carriers that although the totality of the patients is low, the relative percentage is higher in the APOE e4 carriers and by having a lower dose in their patient category we can significantly reduce this event. That had an impact on this design."
Bill Tanner - Leerink Swann
"Okay, and then so then obviously the presumption is that you would not be sparing much efficacy for going with a lower doze for better safety profile I guess."
Kelly Martin
"I just want to remind people that Phase 2 data is blinded and it's not possible for us to answer much more. What we will try to do is give you all a framework for the Phase 3 design as Lars said the investigation we are taking through, through in more details and clearly there we had a unique situation, where with the interim look of Phase 2, there was very specific insight into all of these questions, that was then put into the design of Phase 3. Now optimally we need to wait for the Phase 2 to complete itself and we look at the data. So, the Phase 3 is designed to give ourselves the maximum opportunity to be successful."
Rich Silver - Lehman Brothers
"on Bapineuzumab again and the Phase 3 design, you'd mentioned that it's premature to be discussing whether an interim analysis would be included and that you said that you're still in the process of getting specific feedback from the regulatory agencies, does that also mean that the start timeframe is also yet to be determined?"
Lars Ekman
"No. The start time is fixed and we are on time to dose the first patient before year-end that has not changed. I would say that until we settle all the small details with all authorities, we should not disclose these details (interim analysis). I didn't say that we have this topic (issue open) with all of the authorities and I think at this point we would rather not disclose it."
Rich Silver - Lehman Brothers
"And how Lars, how long do you think it will be before you have the last patient enrolled?"
Lars Ekman
"We have all the trial sites, of course we have our own assumptions..... We hope and we think we can recruit fast for the following reason. One is that there is no big Phase 3 trial ongoing that is competing with this....."
Closing:
"I would reiterate since many of the questions focused on the Phase III design and we are in a quite unique situation where the Phase II is ongoing and its blinded but a very small group of people from Wyeth and Elan had an interim look at the Phase II, and obviously that opportunity allowed us to very, very specifically design a Phase III ......we would hope to get the first patient dosed in North America towards the end of this year or very early part of next year".
"....on the biotech battle-field, you need some élan...."
