WEBVTT 1 00:00:00.520 --> 00:00:04.860 (serene music) 2 00:00:04.860 --> 00:00:06.170 We'd love to hear your thoughts 3 00:00:06.170 --> 00:00:09.490 on how you see innovation on the clinical development side. 4 00:00:09.490 --> 00:00:12.380 It's very hard to see how we're going to handle hundreds 5 00:00:12.380 --> 00:00:16.200 of gene therapies for rare disorders. 6 00:00:16.200 --> 00:00:18.083 There are hundreds of rare disorders 7 00:00:18.083 --> 00:00:19.758 waiting to be addressed, 8 00:00:19.758 --> 00:00:23.770 and trying to get there towards hard clinical endpoints 9 00:00:23.770 --> 00:00:26.200 that meet the statutory standard 10 00:00:26.200 --> 00:00:29.110 of substantial evidence of effectiveness 11 00:00:29.110 --> 00:00:31.580 for the final clinical endpoint 12 00:00:31.580 --> 00:00:35.660 is going to be very challenging for every one of them. 13 00:00:35.660 --> 00:00:38.320 Whereas getting there for substantial evidence 14 00:00:38.320 --> 00:00:41.260 of effectiveness based on a surrogate 15 00:00:41.260 --> 00:00:44.200 to meet the accelerated approval standard, 16 00:00:44.200 --> 00:00:46.300 that's more possible, I think. 17 00:00:46.300 --> 00:00:48.200 So do you see, do you believe then, 18 00:00:48.200 --> 00:00:52.620 that to address the durability issues, we'll need to, 19 00:00:52.620 --> 00:00:55.440 I guess, have a sort of more rigorous approach 20 00:00:55.440 --> 00:00:58.610 to the subsequent trials that are needed 21 00:00:58.610 --> 00:01:01.800 to demonstrate effect over the long term? 22 00:01:01.800 --> 00:01:04.020 Or how do you see the balance between what's done 23 00:01:04.020 --> 00:01:05.300 in the clinical trial setting 24 00:01:05.300 --> 00:01:07.580 versus the real world observations? 25 00:01:07.580 --> 00:01:09.740 Yeah, so I mean, the balance here 26 00:01:09.740 --> 00:01:12.280 is dealing with what the underlying disorder is, 27 00:01:12.280 --> 00:01:16.690 because for a disorder that kills a child 28 00:01:16.690 --> 00:01:19.891 within five to seven years of life, 29 00:01:19.891 --> 00:01:24.470 a durability of something that gets you five to ten years 30 00:01:24.470 --> 00:01:26.940 is what parents will take because they'll say, look, 31 00:01:26.940 --> 00:01:29.677 if I can get five to ten years out of this gene therapy, 32 00:01:29.677 --> 00:01:32.470 something will come along next 33 00:01:32.470 --> 00:01:34.930 at generation two that I'll take. 34 00:01:34.930 --> 00:01:38.820 On the other hand, if you have shorter durability, 35 00:01:38.820 --> 00:01:40.220 that could be an issue. 36 00:01:40.220 --> 00:01:45.220 The other issue is that, 37 00:01:45.482 --> 00:01:47.240 when you start to think about this 38 00:01:47.240 --> 00:01:50.720 for more common disorders 39 00:01:50.720 --> 00:01:53.250 for which there might be an alternative therapy, 40 00:01:53.250 --> 00:01:58.250 then the analysis gets complicated by the economics 41 00:01:58.540 --> 00:02:00.000 of what you're doing as well. 42 00:02:00.000 --> 00:02:03.700 In other words, what can you actually charge for something 43 00:02:03.700 --> 00:02:07.720 that only gives you five years of correction on average 44 00:02:07.720 --> 00:02:11.680 when you can give another drug 45 00:02:11.680 --> 00:02:15.120 for that same five years, and it will cost less? 46 00:02:15.120 --> 00:02:20.120 So what is the incremental benefit of not needing 47 00:02:20.350 --> 00:02:23.540 to infuse yourself once a week, or once every two weeks? 48 00:02:23.540 --> 00:02:26.500 And that gets to be more complicated. 49 00:02:26.500 --> 00:02:28.500 I'm not sure I have all the answers to this, 50 00:02:28.500 --> 00:02:32.100 but there's a lot of calculus that goes into here 51 00:02:32.100 --> 00:02:34.600 that I don't think we've worked all of it out yet.