I'm still bemoaning amev's sellout :-)
MEDI q cc amev related comments, quite a bit of analyst interest and color on numax and vitaxin.....
On the Numax front, our next-generation RSV antibody, we
continued enrolling patients in our pediatric Phase I/II safety and PK trials. We also initiated a Phase I RSV treatment trial involving 30 patients during the quarter and continued making progress on planning our Phase III development program for this molecule. We hope to begin that Phase III program in 2005. Numax as you probably remember is our third-generation antibody targeting RSV. In preclinical studies it has been shown to be 50- to 100-fold more potent than Synagis in helping to reduce RSV replication in both the lower and upper airway in animal models. Synagis has been successful in its ability to reduce RSV in the lower airway in infants, but if Numax is approved and can also be shown to reduce the virus in the upper airway, it could be a significant improvement and open the door to decrease the incidence and severity of upper respiratory tract infections and otitis media, reduce wheezing and reactive airway disease, as well as decrease RSV hospitalizations overall. I remind you that one of the other potential financial upsides to this molecule is that we have the full worldwide marketing
and financial rights which would allow us to retain the significant copromotion fees we now pay Abbott Laboratories for their part in U.S. Synagis sales.
Let me now give you a brief update on some additional pipeline activities in the first quarter. As you know, since last year we have had four Phase II trials with Vitaxin under way, each targeting a different patient group, including melanoma patients, patients with prostate cancer, rheumatoid arthritis patients, and psoriasis patients. During the first quarter we completed patient
enrollment in both the psoriasis and rheumatoid arthritis trials.
Enrollment in the melanoma study is well along, reaching
approximately 90 patients as of today out of a targeted
enrollment of about 110 patients; and we expect enrollment to be concluded in the second quarter in that trial. As the program for Vitaxin continues to move forward, we remain on target to have data from these trials this year and to hopefully be in a position to decide if and how to proceed to Phase III in 2005.
Q&A: Geller, CIBC
On Vitaxin, can you give us any sense about what indications you're most enthusiastic about, and when we would be getting some indication of, say, efficacy and safety on Vitaxin for various indications? Thanks.
On the Vitaxin question, what indications are you particularly excited about? Interestingly enough, on my way in the building this morning to come up here for this phone call I stopped by the MediCafe on the first floor to pick up my cup of coffee, and I ran into Dirk Reitsma and Jim Pluta, two of our oncology research physicians, who were breaking bread in the cafeteria together this morning. I went by and started pummeling them for information on Vitaxin, because I am so excited about
the oncology indications for Vitaxin. I think one of the ones that all of us are very anxious to get results on right now is the metastatic melanoma study which is
ongoing. As I mentioned in my comments, we have now gotten
enrollment in that study up to 89 or 90 patients, out of a target of 110 patients. So we are really tracking right on the curve we want them to be for enrollment in that program. Our targeted total enrollment is 110 patients.
The design of that study is one arm is DTIC which is the
standard of care in those patients. The other arm is DTIC plus Vitaxin. We're hoping to see, frankly, ultimately longer survival in those patients who tend to have very short expectations for survival, three to four months or even less depending on how late-stage the patients are.
So, there is the ability to see a pretty big impact in terms of keeping people alive with the product potentially in that indication. I think we're quite excited about that, because not only is it medically important and commercially a large opportunity but it is also an indication which can be studied relatively rapidly, as shown by how quickly we have enrolled patients in the Phase II study. We could do a Phase III pretty promptly. And patients reach endpoints unfortunately quite quickly. So I think that is an indication that, were we to see
some promise there, we would all be very excited about because it could move very, very quickly.
I think the prostate cancer study, which is also ongoing in Phase II right now, is likely to be slower not only in terms of enrollment but also in terms of how long it will take to get meaningful readouts from the study. So we are going to have to be a little more patient on that one.
Then, RA and psoriasis are interesting. Frankly the psoriasis study I view more as a biological marker study than a direct path to commercialization. Because until we see a result, I'm not looking at that as an immediate commercial opportunity, but an opportunity to understand how is this molecule working in those patients. Because you can recruit very quickly. You can get very quick readouts. And we expect it to have a meaningful impact on the course of disease in those psoriasis patients. But we need to see how big that impact is and compare it to
the other therapies in the biologic arena that have recently come to market before we can make a decision as to whether or not to go forward in commercial development in psoriasis.
The RA market I think is obviously very exciting, because it is huge. A huge commercial opportunity. But again sort of like psoriasis, the bar is pretty high at the moment in terms of what you have to show.
Net-net, when I look at those four Phase IIs that we're looking at right now, the one that I am particularly anxious to get some results on, for the reasons I have articulated, is the metastatic melanoma trial.
Maykin Ho, GS
The second is on the start of the Phase III trial for Numax. I thought that was going to be at the end of this year, and you just mentioned it's 2005. I'm not sure that I heard it correctly. And what is the reason for the delay?
With respect to the Numax, I am not sure what the basis of the confusion is. Let me just be real specific on exactly where we are with the Numax program. It has not changed. In fact, if anything, we're ahead of where we expected to be. We are driving very, very hard with that program. We have large Phase I/II programs going on now in the northern hemisphere, both. We have done healthy adult volunteer studies. We've done single-dose pediatric studies. We are now doing multiple-dose pediatric studies at the target dosing level of 15 mg/kg monthly.
We have now also begun a treatment study looking for antiviral effect in intubated patients. And we have many centers lined up in the southern hemisphere to begin studies in the April-May-June time frame as their season begins and our season up here winds down, to continue to build the safety data set that we think is appropriate to support moving forward into pivotal studies. It is possible that we could, if everything goes right, have the
opportunity to accelerate the program and began a Phase III as early as this fall. But that is a real stretch, an aggressive program; and we have not yet had the opportunity to meet with the FDA and discuss those objectives. And we need to get some of the data in from the Phase I/II trials to be able to credibly go meet
with the FDA and discuss those things. So, our current base assumption is, as it has been consistently,
that the Phase III program will really be underway in '05; perhaps beginning in the southern hemisphere season in '05, moving into the northern hemisphere for the fall-winter season, and then hopefully finishing up in the southern hemisphere in their next season. If we're fortunate enough to be able to accelerate, then we could do it in the northern hemisphere in the '04-'05 season, have some southern hemisphere in the summer of '05, and then finish it up in the northern hemisphere in the '04-'05.
We don't know which one of those will pan out at this point. I think that given the aggressiveness of getting in this fall the appropriate assumption is '05. But trust that we will do everything we possibly can to accelerate it into '04.
Mark Augustine - CS First Boston - Analyst
I wanted to ask about the Numax program, because I was under the impression that the use of the southern hemisphere this calendar year would be in the context of a Phase II study of approximately 500 patients. Given that you haven't changed any of your guidance, we know that. But the discussion of a more aggressive planned Phase III, would that preempt or skip through the Phase II? And why would you do that?
David Mott - MedImmune - President & CEO
Sure. To do a Phase II that large, would mean that we would
not be doing Phase III in the fall of '04-'05. So, if we do not succeed in accelerating the program, then I would expect us to recruit -- we probably won't get 500 patients in the southern hemisphere, but it will continue rolling. We will keep the program rolling that is in the northern hemisphere now. Roll it through the southern hemisphere, and then continue back into the northern hemisphere collecting Phase II data. And that would be on the order of a 500-patient kind of Phase II program. The alternate would be that if everything goes extraordinarily well we will end up with more like 200 patients' worth of Phase II data from this year's northern hemisphere, some southern
hemisphere. And that is all we can really get in time to accelerate into a Phase III this fall. So, the larger Phase II program is a fall-back if you can't get into Phase III in the '04-'05 season.
Mark Augustine - CS First Boston - Analyst
Would you have an efficacy comparator in Phase II or Phase
III? I guess I am wondering if your envisioned head-to-head
remains as you laid out back in the analyst day from June, a head-to-head with Synagis providing broader protection against viruses of interest, what would be the benefit of entering the great unknown of a head-to-head study directly from Phase I to Phase III? Or have your plans changed for Phase III?
David Mott - MedImmune - President & CEO
Our plans haven't changed in any way for Phase III. I'm not
sure what you really mean about broader coverage. Numax is
specific against RSV just as Synagis is. So we would not expect broader coverage against any other viral pathogens. We would hope to have potentially greater efficacy because of the greater potency, and potentially block upper respiratory infections which could produce asthma, wheezing, those kinds of things. The limitations on Phase II in a prophylactic study are ones that we have lived with for many years in developing RSV products more than a decade. Because you really can't learn much in terms of efficacy from Phase IIs. Because if you have an underlying RSV hospitalization rate that, depending on what
population and what literature you look at, is anywhere from 10 to 20 percent or 10 to 25 percent, it takes a very large number of patients before you can learn something.
If you are trying to look at comparative efficacy between Synagis and Numax, you've got to multiply that by a large factor in terms of the number of patients who would be required to show it. So frankly, the role of Phase I/II in RSV development is really a safety role. You might get some signals of benefit, but it is unlikely that you're going to be able to tell much in terms of relative efficacy from a Phase II program, even a 500-patient
Phase II program. So, all that does is give you additional safety information that makes you more comfortable going into Phase III. But it really doesn't help you with the efficacy questions that have to be asked in Phase III. Our strategy for Phase III does continue to be to compare the efficacy of Numax to that seem with Synagis in preventing RSV hospitalizations. And that would be the primary endpoint, is comparative efficacy between the two in RSV hospitalization rates.
Eric Ende - Merrill Lynch - Analyst
One last question on Numax. How large a study would you
really have to do comparing Numax to Synagis to show
superiority?
David Mott - MedImmune - President & CEO
We're looking at a Phase III trial design of between 5 and 6,000 patients. A head-to-head study of 5 to 6,000 patients. One-to-one randomization, Synagis versus Numax. |
