so today we’ve said that we do plan on keeping a subset of our assets longer and what we plan to do is have a different business development strategy for each asset depending on its characteristics. The characteristics of drugs that we’d keep longer are programs where we think the Phase 2 clinical trials will substantially derisk the asset; programs where we have internal expertise, so we know that we can create a Phase 2 clinical development plan that’s as good as the Phase 3 clinical development plan at any large pharmaceutical company can create; programs where we have external networks, KOLs, consultants, we know the doctors, we know the clinical trials that we run, so that it isn’t just a question of being good in the therapeutic area and hiring one or two doctors who happened to know it. The relationships that you build over a lengthy period of time are very important in implementing a Phase 3 clinical trial program.
In addition, obviously the Phase 3 clinical development has to be manageable. So we’re talking about smaller indications with shorter time to a clinical efficacy endpoint. The first drive that meets all of these criteria is our apoC-III inhibitor, ISIS-APOCIIIRx. That’s a drug that where our initial development passes in patients with severely elevated triglycerides. So triglycerides levels over 880 milligrams per deciliter its about 50,000 patients in the U.S. were finishing up the Phase 2 program in the middle of the year that we plan to take those data to the regulatory agencies in the U.S. and Europe finalize our Phase 3 clinical plan and start the Phase 3 clinical program early next year.
Okay, so it seems like you have a good handle on the efficacy of this product and it definitely does lower triglycerides very materially, but I guess one question, a question on safety. Have you seen any signals in other studies and that concern you of the upcoming data sets?
We have not and recall that this is one of the more advanced generation two compounds we have, so we would expect to see much fewer and milder injection site reactions and much less frequent flu like symptoms in this extremely high risk patient population we’re hoping for a safety profile that’s very benign and very attractive.
The Kynamro launch is going well. It’s going the way we expect it to. We think actually given the very different profiles of these two drugs, its going to take time, maybe 12, 18 months before the patients really sort themselves out based on combinations of efficacy and safety and compliance with the two different drugs and we’re pleased at the efforts our partners making to characterize those issues with physicians and we’re really pleased with the uptake that those ideas are having with the physicians.
what's your plans on getting KYNAMRO on the market for, in the EU now?
So, we did have a negative opinion from the CHMP, and we have an ongoing study called the FOCUS-FH study in severe heterozygous FH patients which we’re doing under a SPA with the FDA to expand the indication in the U.S. assuming those data are positive. Genzyme plans to use those data to go back and re-file in Europe as well as filing in the U.S. to expand the indication. And that study will finish up at the end of next year.
Spinal Muscular Atrophy (SMA)
We are currently conducting two Phase 2 clinical trials in this program, one in the childhood onset form of the disease, and one in the infant form of the disease which is a fatal form of the disease where the babies generally die before their second birthday. We plan on finishing up both those studies this year to support Phase 3 clinical trials in both of those patient populations early next year.
Now the clinical trials you just mentioned in the children and infants; are they placebo controlled or are they just single arm studies?
They are not [placebo controlled]. Both of those studies are studies intended to help us finalize our dose and schedule for Phase 3, and so there’s no reason to essentially waste patients by giving them placebos in those studies. We want to get to the fastest answer to finalize our doses so that we can start the studies that are really going to rigorously examine the drug which is the Phase 3 studies. We will have efficacy endpoints built in, but they won't have placebo control.
Is there anything you can do to protect your study from a placebo effect?
Well, I think you do several things which is you make your stay long enough and large enough to do that, and that’s what we are designing. So our Phase 3 clinical trial one of the Type II and Type III children we expect to have approximately 100 or a little bit more patients with a year or so of dosing and we’re designing a very robust study so that we can identify. So that even if placebo patients respond or respond for a period of time based on the enthusiasm of their parent or something like that, that we will have a study design that’s rigorous enough to distinguish.
Now is this a type of product that can get break though designation from the FDA?
I think it should be. It will be an example that the FDA used in some of their commentary, Spinal Muscular Atrophy as the disease in which break through could be your failure.
And I’m guessing you’re in talks with them about this?
We’re going to talk to them about it. Yeah, I mean they say you need Phase 2 clinical data in order to …
Phase 2 or, so you’ll have the Phase 2 data by end of this year, and then you’ll talk to them about it.
Yeah....But that being said, we have had a tremendously positive dialogue with the FDA about this drug. We haven't found that there are any barriers to interactive discussions with them about the program.