1 00:00:00,360 --> 00:00:03,080 Speaker 1: In the fall of two thousand seven, a twenty three 2 00:00:03,120 --> 00:00:05,320 Speaker 1: year old man went to see a doctor in Padua, 3 00:00:05,559 --> 00:00:08,000 Speaker 1: sitting near Venice in the north of Italy. He had 4 00:00:08,039 --> 00:00:13,520 Speaker 1: a blood clot in his leg. The whole case was unusual. 5 00:00:14,040 --> 00:00:16,720 Speaker 1: The man was young and healthy, and he didn't take drugs. 6 00:00:17,239 --> 00:00:20,120 Speaker 1: It turns out that the patient, whose name is still 7 00:00:20,120 --> 00:00:22,840 Speaker 1: a secret, had a genetic mutation in his d N 8 00:00:22,960 --> 00:00:26,360 Speaker 1: A somebody so rare that it had actually never been 9 00:00:26,360 --> 00:00:28,680 Speaker 1: seen before. Yeah, it made a big impression on the 10 00:00:28,760 --> 00:00:33,400 Speaker 1: doctor who saw him that day. Dr Paolo Simione I 11 00:00:33,400 --> 00:00:39,440 Speaker 1: immediately realized the importance of this same mutation in a 12 00:00:39,520 --> 00:00:47,519 Speaker 1: completely different context. They therapy. Gene therapy is an emerging 13 00:00:47,560 --> 00:00:50,360 Speaker 1: area of medicine generating a lot of excitement right now. 14 00:00:50,760 --> 00:00:53,440 Speaker 1: If it works, it could transform the lives of people 15 00:00:53,479 --> 00:00:56,880 Speaker 1: who suffer from thousands of different conditions caused by tiny 16 00:00:56,920 --> 00:01:00,760 Speaker 1: abnormalities in their d NA. It turns out that young 17 00:01:00,800 --> 00:01:04,360 Speaker 1: man in Padua had walked into Dr Simone's office with 18 00:01:04,480 --> 00:01:08,319 Speaker 1: a possible cure. You see, his blood clotted too easily. 19 00:01:08,800 --> 00:01:13,600 Speaker 1: A protein responsible for blood clotting was too active or supercharged. 20 00:01:13,880 --> 00:01:16,959 Speaker 1: But about twenty six thousand people around the world suffer 21 00:01:17,000 --> 00:01:20,560 Speaker 1: from an opposite condition, hemophilia B. When most of us 22 00:01:20,600 --> 00:01:23,959 Speaker 1: bleed are blood naturally forms a clot so the bleeding stops. 23 00:01:24,160 --> 00:01:27,240 Speaker 1: But this natural mechanism doesn't happen in people with severe 24 00:01:27,280 --> 00:01:31,000 Speaker 1: hem ophelia, which means that even with a relatively minor injury, 25 00:01:31,000 --> 00:01:34,800 Speaker 1: people with this condition could suffer from serious internal bleeding. 26 00:01:35,560 --> 00:01:39,760 Speaker 1: He was Betty, Betty Vitty excited by this fact that 27 00:01:40,120 --> 00:01:45,120 Speaker 1: this might be a real treatment for remostly. Indeed, hemophilia B, 28 00:01:45,680 --> 00:01:49,760 Speaker 1: the disease that famously plagued European royal families for generations 29 00:01:50,560 --> 00:01:54,040 Speaker 1: thanks to Paulo Simyonis discovery back in two thousand and seven, 30 00:01:54,520 --> 00:01:57,440 Speaker 1: scientists have been working on a new treatment that is 31 00:01:57,480 --> 00:02:00,840 Speaker 1: now being tested on patients with him ophilia B. And 32 00:02:01,040 --> 00:02:04,240 Speaker 1: unlike the frequent hospital visits and infusions patients have had 33 00:02:04,280 --> 00:02:07,280 Speaker 1: to put up with their whole lives, this is potentially 34 00:02:07,360 --> 00:02:23,519 Speaker 1: a one time treatment. Hi. I'm Brad Stone and I'm Donnyloomfield, 35 00:02:23,600 --> 00:02:26,000 Speaker 1: and this week on Decrypted, we're taking you to the 36 00:02:26,040 --> 00:02:28,720 Speaker 1: frontiers of science where we're starting to see the first 37 00:02:28,760 --> 00:02:32,760 Speaker 1: effective gene therapies, treatments that could rewrite the lives of 38 00:02:32,800 --> 00:02:37,080 Speaker 1: people living with genetic disease. Will follow one patient, in particular, 39 00:02:37,400 --> 00:02:40,760 Speaker 1: j Con Duros, on his journey through an experimental trial 40 00:02:40,840 --> 00:02:44,720 Speaker 1: to effectively get rid of his hemophilia. The potential cures 41 00:02:44,760 --> 00:02:47,400 Speaker 1: are setting the stage to one day upset the ten 42 00:02:47,440 --> 00:02:52,640 Speaker 1: billion dollar hemophilia market and even the gigantic billion dollar 43 00:02:52,760 --> 00:02:57,200 Speaker 1: rare disease market dominated by genetic conditions like hemophilia. A 44 00:02:57,280 --> 00:02:59,919 Speaker 1: small number of companies are on the brink of transform 45 00:03:00,040 --> 00:03:02,720 Speaker 1: into space. Will go inside the lab at one such 46 00:03:02,800 --> 00:03:06,280 Speaker 1: startup to explain the biotech breakthrough and how it's changed 47 00:03:06,360 --> 00:03:09,000 Speaker 1: Jay's life. Plus we'll take a look at the challenging 48 00:03:09,080 --> 00:03:22,320 Speaker 1: road ahead. So, Donnie, you're a biotech reporter. In simple terms, 49 00:03:22,560 --> 00:03:25,919 Speaker 1: let's explain to our listeners and frankly to me, what 50 00:03:26,080 --> 00:03:30,160 Speaker 1: gene therapy actually is. Genes are the underlying code of life. 51 00:03:30,480 --> 00:03:34,160 Speaker 1: Humans have about twenty thou genes in their DNA, and 52 00:03:34,320 --> 00:03:37,440 Speaker 1: the different genes they produce different kinds of proteins, which 53 00:03:37,680 --> 00:03:40,720 Speaker 1: turn out into all different kind of characteristics that show 54 00:03:40,800 --> 00:03:43,640 Speaker 1: up in our body, like our hair color, eye color, 55 00:03:43,720 --> 00:03:46,200 Speaker 1: or how likely we are to get breast cancer. By 56 00:03:46,200 --> 00:03:49,680 Speaker 1: the same token, they can cause real problems when they're 57 00:03:49,680 --> 00:03:52,120 Speaker 1: messed up. Or when we have a bad mutation or body. 58 00:03:52,400 --> 00:03:55,080 Speaker 1: And sometimes people might be missing a particular gene, or 59 00:03:55,160 --> 00:03:57,840 Speaker 1: they might have a mutation that means their bodies don't 60 00:03:57,840 --> 00:04:00,560 Speaker 1: operate normally. So the ideas gene therapy and fix it. 61 00:04:00,600 --> 00:04:03,760 Speaker 1: Are you replacing a gene. The idea is, let's give 62 00:04:03,800 --> 00:04:07,960 Speaker 1: these people a good gene, properly functioning gene that allows 63 00:04:08,000 --> 00:04:11,200 Speaker 1: them to effortlessly start producing the proteins that they need 64 00:04:11,600 --> 00:04:14,200 Speaker 1: from having the good gene in their body. So, being 65 00:04:14,200 --> 00:04:16,919 Speaker 1: a tech guy, I think about this like altering a 66 00:04:16,920 --> 00:04:19,599 Speaker 1: little piece of computer code to make make the computer 67 00:04:19,800 --> 00:04:23,440 Speaker 1: function differently. Is that's sort of right. So in this case, 68 00:04:23,480 --> 00:04:26,360 Speaker 1: it's not altering a code, it's giving people a new code. 69 00:04:26,640 --> 00:04:29,039 Speaker 1: And when you give people that new code, they can 70 00:04:29,120 --> 00:04:31,880 Speaker 1: run that, and you can think about a cell almost 71 00:04:31,880 --> 00:04:34,720 Speaker 1: like running a piece of software which ultimately turns into 72 00:04:34,760 --> 00:04:38,160 Speaker 1: these proteins. Of course, there is a big difference. You 73 00:04:38,200 --> 00:04:41,000 Speaker 1: can't just try out whatever kind of code you want 74 00:04:41,040 --> 00:04:43,839 Speaker 1: on people because even a little change can make a 75 00:04:43,920 --> 00:04:46,800 Speaker 1: huge difference. They could hurt someone, that could kill someone. 76 00:04:47,200 --> 00:04:49,720 Speaker 1: You have to be super cautious. You know exactly what 77 00:04:49,839 --> 00:04:55,800 Speaker 1: different code you're putting into someone's body. So this concept 78 00:04:55,839 --> 00:04:59,120 Speaker 1: of gene therapy has been around for a while now, right, Yeah, 79 00:04:59,160 --> 00:05:02,360 Speaker 1: but it has gone mainstream. So far, there have been 80 00:05:02,480 --> 00:05:05,719 Speaker 1: very few large trials and people, and most studies so 81 00:05:05,760 --> 00:05:09,480 Speaker 1: far haven't gone right, they've failed. But recently these treatments 82 00:05:09,560 --> 00:05:12,400 Speaker 1: have started making the way of real patients Like Jay. 83 00:05:13,360 --> 00:05:15,720 Speaker 1: As soon as I had any knowledge of anything, I 84 00:05:15,800 --> 00:05:19,719 Speaker 1: knew that I had humophilia because um it had been 85 00:05:19,760 --> 00:05:24,680 Speaker 1: diagnosed before, like by the time I was born. So 86 00:05:24,720 --> 00:05:27,120 Speaker 1: I actually techniques beak of not missing the factory nine. 87 00:05:27,160 --> 00:05:30,599 Speaker 1: The factory nine my body creates is creates a lot 88 00:05:30,640 --> 00:05:37,320 Speaker 1: of it, but it's misshapen. It doesn't work properly. Factor nine. 89 00:05:37,600 --> 00:05:39,680 Speaker 1: We're going to hear a lot more about that today. 90 00:05:40,440 --> 00:05:42,880 Speaker 1: It's a protein found in our blood if we get 91 00:05:42,880 --> 00:05:45,360 Speaker 1: a cut and start bleeding, Factory nine is a key 92 00:05:45,400 --> 00:05:47,880 Speaker 1: part of the system in our bodies that stops the bleeding. 93 00:05:48,400 --> 00:05:51,359 Speaker 1: The fact that Jay's genes don't produce a functioning version 94 00:05:51,360 --> 00:05:55,400 Speaker 1: of this protein has had a major impact on this life. Yeah. 95 00:05:55,640 --> 00:05:59,160 Speaker 1: Jay grew up in Canada, Montreal and Toronto. He says, 96 00:05:59,160 --> 00:06:05,640 Speaker 1: the childhood was pretty normal Montre. All days were just 97 00:06:05,800 --> 00:06:10,599 Speaker 1: your typical sixties seventy family life. I guess the father working, 98 00:06:10,720 --> 00:06:14,320 Speaker 1: mother homemaking, and kids doing what kids do. But my 99 00:06:14,640 --> 00:06:19,000 Speaker 1: very earliest memories are definitely the Volkswagen Peace Love vans 100 00:06:19,120 --> 00:06:21,800 Speaker 1: and uh that's sixties vibe. I think it's in my 101 00:06:21,880 --> 00:06:30,440 Speaker 1: soul for sure about it. For Jay, everything was normal 102 00:06:30,920 --> 00:06:34,880 Speaker 1: except a hemophilia. How would you explain him afiliate to 103 00:06:35,000 --> 00:06:38,720 Speaker 1: people if you did believe it or not. I've never 104 00:06:38,839 --> 00:06:43,080 Speaker 1: breach approached the topic. For me personally, I've avoided any 105 00:06:43,160 --> 00:06:45,320 Speaker 1: talk about it or to the point of leaving a 106 00:06:45,400 --> 00:06:51,480 Speaker 1: room if it's the discussions that got that way. As 107 00:06:51,480 --> 00:06:54,279 Speaker 1: a kid, Jay's friends would play hockey in the street 108 00:06:54,720 --> 00:06:58,600 Speaker 1: or wrestle for fun. But because of Jay's hemophilia, what 109 00:06:58,720 --> 00:07:01,080 Speaker 1: would have been regular scray and bruises for one of 110 00:07:01,080 --> 00:07:04,400 Speaker 1: his friends would mean Jay's mother rushing into the hospital. 111 00:07:05,520 --> 00:07:08,400 Speaker 1: Those things, even as a kid, were terrifying to me. 112 00:07:09,160 --> 00:07:14,040 Speaker 1: Those things, would, you know, end up putting you out 113 00:07:14,040 --> 00:07:17,560 Speaker 1: of commission kind of for you know, going to school 114 00:07:17,600 --> 00:07:19,840 Speaker 1: for a couple of weeks at a time or even more, 115 00:07:20,280 --> 00:07:24,200 Speaker 1: and then you'd be limping for another month recovering. So 116 00:07:24,200 --> 00:07:28,520 Speaker 1: so since you'd know what's gonna happen, those kind of 117 00:07:28,520 --> 00:07:36,120 Speaker 1: injuries were, Yeah, they get head towards being kind of terrifying. Today, 118 00:07:36,360 --> 00:07:38,960 Speaker 1: Jay is fifty three years old and he isn't playing 119 00:07:38,960 --> 00:07:41,920 Speaker 1: hockey in the streets anymore. Umphilia has become something he 120 00:07:42,000 --> 00:07:44,600 Speaker 1: learned to live with. He and his wife Yolanta run 121 00:07:44,600 --> 00:07:48,160 Speaker 1: a bakery called Nougat in Kitchener, Ontario. Hi, Lacy, it 122 00:07:48,280 --> 00:07:50,840 Speaker 1: is newgat bakery, J speaking, can I put it in 123 00:07:50,960 --> 00:07:57,920 Speaker 1: order for tomorrow? Almonds blenched meal, T pounds one box almond. 124 00:07:58,120 --> 00:08:01,240 Speaker 1: For years, Jay has managed a hemophilia with a portable 125 00:08:01,280 --> 00:08:03,520 Speaker 1: kit keeps with him so we can give himself an 126 00:08:03,560 --> 00:08:06,240 Speaker 1: infusion of the factor nine protein when he's worried about 127 00:08:06,240 --> 00:08:10,240 Speaker 1: a bleed. Despite that, a single bump, even if properly treated, 128 00:08:10,280 --> 00:08:13,000 Speaker 1: could still swell up with internal bleeding and turn into 129 00:08:13,000 --> 00:08:16,880 Speaker 1: a medical nightmare. For example, but in just a couple 130 00:08:16,920 --> 00:08:19,200 Speaker 1: of years ago, I ended up. I was shoveling snow 131 00:08:19,280 --> 00:08:24,960 Speaker 1: and this shovel cut the the ashphalts and the tip 132 00:08:25,000 --> 00:08:28,440 Speaker 1: of the shovel, which rotated the handle sideways into my thigh. 133 00:08:29,360 --> 00:08:33,920 Speaker 1: An everyday incident like this could be really dangerous for Jay. 134 00:08:34,000 --> 00:08:36,120 Speaker 1: Knew that was going to cause a bruise for sure, 135 00:08:36,160 --> 00:08:38,920 Speaker 1: so I actually went home and getting myself a treatment 136 00:08:39,000 --> 00:08:42,560 Speaker 1: right away. That's a factor nine infusion. Kid. Jay keeps 137 00:08:42,559 --> 00:08:44,840 Speaker 1: at home, and then ended up being in the hospital 138 00:08:44,880 --> 00:08:51,920 Speaker 1: for ten days and I was kind of on on 139 00:08:52,640 --> 00:08:56,680 Speaker 1: steady dose factor nine treatment for the next month. I think, 140 00:08:57,160 --> 00:09:02,160 Speaker 1: you know doctor's orders, and um, well it's on crutches. 141 00:09:02,200 --> 00:09:05,200 Speaker 1: I think for another three weeks after I got to 142 00:09:05,240 --> 00:09:08,920 Speaker 1: the hospital, and then on a cane and for another 143 00:09:09,440 --> 00:09:11,880 Speaker 1: three months, and I think there was another three months 144 00:09:11,960 --> 00:09:16,720 Speaker 1: after that before you'd say I was back to the 145 00:09:16,760 --> 00:09:20,560 Speaker 1: shape I was in before. I just can't imagine how 146 00:09:20,600 --> 00:09:24,640 Speaker 1: disruptive to his life hemophilia has been. I would imagine 147 00:09:24,679 --> 00:09:27,800 Speaker 1: Donnie that he he really leapt at the opportunity when 148 00:09:27,880 --> 00:09:31,440 Speaker 1: doctors told him, uh, they could cure as hemophilia. Well, 149 00:09:31,520 --> 00:09:33,880 Speaker 1: I don't think anyone was promising a cure. But a 150 00:09:33,960 --> 00:09:37,239 Speaker 1: year ago Jay's doctor did tell him about an experimental 151 00:09:37,280 --> 00:09:40,640 Speaker 1: trial with a company called Spark Therapeutics, and they're based 152 00:09:40,640 --> 00:09:44,439 Speaker 1: in Philadelphia. The goal of the trial seemed outlandish. Spark 153 00:09:44,559 --> 00:09:46,839 Speaker 1: was testing a new kind of therapy, like you said, 154 00:09:47,200 --> 00:09:50,840 Speaker 1: that would require one visit to the hospital and maybe 155 00:09:51,000 --> 00:09:54,200 Speaker 1: after just one visit, Jay would see the symptoms of 156 00:09:54,200 --> 00:10:04,400 Speaker 1: his hemophilia start to disappear. Are you telling me that 157 00:10:04,520 --> 00:10:06,760 Speaker 1: you can have a disease your whole life because of 158 00:10:06,880 --> 00:10:09,520 Speaker 1: so much drama and you have to have these injections. 159 00:10:09,520 --> 00:10:14,319 Speaker 1: They come with their own risks of infection of you know, viruses. 160 00:10:14,800 --> 00:10:17,680 Speaker 1: But all of a sudden, you can walk into some buildings, 161 00:10:17,679 --> 00:10:20,679 Speaker 1: sit in a chair, have someone put an intravenous need 162 00:10:20,760 --> 00:10:24,920 Speaker 1: on you for maybe an hour forty five minutes to 163 00:10:24,920 --> 00:10:27,400 Speaker 1: an hour, and drip a clear bag of liquid into 164 00:10:27,480 --> 00:10:31,880 Speaker 1: you and that's it. Pulled the needle out and go home. 165 00:10:33,440 --> 00:10:36,000 Speaker 1: After talking over with his wife, he designed to sign 166 00:10:36,040 --> 00:10:39,040 Speaker 1: up and we said down and we talked about it, 167 00:10:39,080 --> 00:10:42,960 Speaker 1: and I thought it was a great idea. Uh, there 168 00:10:43,000 --> 00:10:46,480 Speaker 1: are no huge side effects on that. I'm like, you 169 00:10:46,520 --> 00:10:50,200 Speaker 1: have nothing to lose. The word that comes into my mind, 170 00:10:50,240 --> 00:10:52,000 Speaker 1: I don't want to even say it, but but you 171 00:10:52,000 --> 00:11:01,560 Speaker 1: could say it's a it's a joke. The company behind 172 00:11:01,559 --> 00:11:04,679 Speaker 1: the trial was called Spark Therapeutics. The company has been 173 00:11:04,679 --> 00:11:07,400 Speaker 1: around for four years and was born when a man 174 00:11:07,520 --> 00:11:11,160 Speaker 1: called Steve Altruler, then the CEO of the Children's Hospital 175 00:11:11,200 --> 00:11:15,240 Speaker 1: of Philadelphia, asked a consultant, Jeff Marazzo, to come to 176 00:11:15,280 --> 00:11:18,520 Speaker 1: the hospital and see did any of the hospital's research 177 00:11:18,559 --> 00:11:22,240 Speaker 1: of commercial potential. And I ended up agreeing with Steve 178 00:11:22,280 --> 00:11:23,800 Speaker 1: that I would spend about three months from in the 179 00:11:23,800 --> 00:11:27,080 Speaker 1: halls of the Children's Hospital Philadelphia meeting with scientists and 180 00:11:27,080 --> 00:11:31,680 Speaker 1: clinicians and people even working on health information technology. That's Jeff, 181 00:11:31,960 --> 00:11:34,800 Speaker 1: who's now the CEO a Spark. And one of the 182 00:11:34,840 --> 00:11:37,000 Speaker 1: last conversations I had was with a woman named Dr 183 00:11:37,200 --> 00:11:42,319 Speaker 1: Katherine High. My name is Dr Cathy High, and I'm 184 00:11:42,360 --> 00:11:46,200 Speaker 1: the president and chief Scientific officer of Spark Therapeutics. And 185 00:11:46,320 --> 00:11:48,720 Speaker 1: our one hour conversation, which I had scheduled with her, 186 00:11:48,840 --> 00:11:51,040 Speaker 1: ended up going about seven hours, and as they say, 187 00:11:51,040 --> 00:11:54,199 Speaker 1: the rest is history. As it turns out, Jeff's timing 188 00:11:54,240 --> 00:11:57,080 Speaker 1: couldn't have been better. I was getting cold calls from 189 00:11:57,160 --> 00:12:01,280 Speaker 1: investors in my office and I didn't want to talk 190 00:12:01,320 --> 00:12:04,640 Speaker 1: to investors. I wanted to do my work. And as 191 00:12:04,679 --> 00:12:06,720 Speaker 1: I was sitting there talking to him, I was thinking, Wow, 192 00:12:06,960 --> 00:12:12,640 Speaker 1: if somebody like this were involved, he could take those calls. Donny, 193 00:12:12,679 --> 00:12:14,800 Speaker 1: you went to go meet Jeff and Cathy in Philadelphia 194 00:12:14,840 --> 00:12:18,360 Speaker 1: the other week, right, Yeah. So, Sparks Labs and offices 195 00:12:18,400 --> 00:12:21,400 Speaker 1: are in the University of Pennsylvania, medical building. It's a 196 00:12:21,480 --> 00:12:25,199 Speaker 1: swanky tower of glass and steel. The bottles sit in 197 00:12:25,240 --> 00:12:27,760 Speaker 1: the roller rack, and then there are rulers here, which 198 00:12:27,800 --> 00:12:31,560 Speaker 1: turned it around. Okay. Kathy has been doing research in 199 00:12:31,559 --> 00:12:34,720 Speaker 1: this area for years, not just in gene therapies, but 200 00:12:34,840 --> 00:12:38,360 Speaker 1: in he ma ophelia specifically. Her earliest projects were looking 201 00:12:38,400 --> 00:12:41,280 Speaker 1: into the proteins that make blood clotting possible, and she 202 00:12:41,360 --> 00:12:45,040 Speaker 1: helped guide patients through the nineties, which was a devastating 203 00:12:45,080 --> 00:12:48,800 Speaker 1: time when most team ophelia patients in the US contracted 204 00:12:48,960 --> 00:12:52,360 Speaker 1: HIV because the factor therapy became infected with the virus 205 00:12:52,840 --> 00:12:57,160 Speaker 1: was very intense term. We uh started to evaluate all 206 00:12:57,200 --> 00:12:59,559 Speaker 1: the people in the clinic and it turned out that 207 00:12:59,640 --> 00:13:03,520 Speaker 1: nearly everyone was positive, but we didn't know what it meant, 208 00:13:03,880 --> 00:13:08,360 Speaker 1: and the and the virologists didn't know what it meant either. 209 00:13:11,720 --> 00:13:16,839 Speaker 1: My first thoughts were, um, I don't remember too much 210 00:13:16,840 --> 00:13:20,160 Speaker 1: because it's very is a panicky feeling because all of 211 00:13:20,200 --> 00:13:23,480 Speaker 1: a sudden, here in this a group of people who 212 00:13:23,520 --> 00:13:31,000 Speaker 1: were um being hunted down by this virus. Many of 213 00:13:31,000 --> 00:13:34,480 Speaker 1: your visions died, many of many of my patients died 214 00:13:35,440 --> 00:13:45,360 Speaker 1: during that time in the nineties and early two thousand's 215 00:13:45,880 --> 00:13:48,640 Speaker 1: Cathy was involved in some of the very first hemophilia 216 00:13:48,720 --> 00:13:53,240 Speaker 1: gene therapy trials. How did those therapies go well? Early on, 217 00:13:53,320 --> 00:13:55,679 Speaker 1: some of the issues was where to actually try and 218 00:13:55,840 --> 00:13:59,600 Speaker 1: deliver the gene. So Cathy tried to deliver the gene 219 00:13:59,600 --> 00:14:02,360 Speaker 1: to muff soul, but it just kept making factor nine 220 00:14:02,640 --> 00:14:05,120 Speaker 1: but it didn't get into the blood, so that wasn't helpful. 221 00:14:05,320 --> 00:14:07,800 Speaker 1: And then they tried to get it into the liver, 222 00:14:07,840 --> 00:14:09,679 Speaker 1: which is where they ended up going. But when they 223 00:14:09,720 --> 00:14:12,720 Speaker 1: did that, the immune system responded. Were their negative side 224 00:14:12,720 --> 00:14:16,840 Speaker 1: effects for the patients that were in those trials not significantly. 225 00:14:17,080 --> 00:14:21,000 Speaker 1: So far these mafiliate trials have been really saved. So 226 00:14:21,120 --> 00:14:24,120 Speaker 1: walk us through how this current trial works. What exactly 227 00:14:24,200 --> 00:14:27,080 Speaker 1: is the treatment sparks testing. The basic idea here is 228 00:14:27,120 --> 00:14:29,600 Speaker 1: you want to deliver a gene, which you can think 229 00:14:29,640 --> 00:14:32,280 Speaker 1: of as like an instruction manual, to the right cells 230 00:14:32,320 --> 00:14:34,400 Speaker 1: that they can make the right protein. And they do 231 00:14:34,440 --> 00:14:37,480 Speaker 1: that all by needing to start with a transportation device. 232 00:14:37,760 --> 00:14:40,160 Speaker 1: And in this case, they take a virus, which sounds 233 00:14:40,160 --> 00:14:43,840 Speaker 1: really scared. The virus does not sound like something you 234 00:14:43,840 --> 00:14:46,600 Speaker 1: want in your body. Yeah, that's right. But what they 235 00:14:46,600 --> 00:14:48,600 Speaker 1: did was they found a harmless one. They found these 236 00:14:48,680 --> 00:14:51,360 Speaker 1: naturally occurring harmless viruses, and you can think of them 237 00:14:51,400 --> 00:14:55,240 Speaker 1: like you know biological transportation system. The idea is that 238 00:14:55,280 --> 00:14:57,640 Speaker 1: they have this factory nine gene in them. They swarm 239 00:14:57,720 --> 00:15:00,200 Speaker 1: into the body, their billions of them, they swim him 240 00:15:00,280 --> 00:15:03,640 Speaker 1: through the blood, and their designs that they're gonna laser 241 00:15:03,720 --> 00:15:06,280 Speaker 1: in and hone in on those liver cells, which is 242 00:15:06,320 --> 00:15:09,280 Speaker 1: kind of the body's factory from making things. Is it 243 00:15:09,320 --> 00:15:13,960 Speaker 1: too early right now to draw any conclusions about sparks trial. Well, 244 00:15:14,040 --> 00:15:17,840 Speaker 1: they've actually had fairly encouraging results. It is small, but 245 00:15:18,040 --> 00:15:22,520 Speaker 1: they've shown that in ten people they can create pretty 246 00:15:22,560 --> 00:15:25,400 Speaker 1: high levels of fact or nine and that's the clotting 247 00:15:25,440 --> 00:15:27,840 Speaker 1: thing that that these people need. And what they've been 248 00:15:27,840 --> 00:15:29,800 Speaker 1: able to find was that nine out of ten people 249 00:15:30,080 --> 00:15:34,920 Speaker 1: haven't had any bleeds since they took this therapy. Is 250 00:15:35,040 --> 00:15:38,760 Speaker 1: Cathy confident that this will work? She is pretty confident. 251 00:15:38,800 --> 00:15:40,480 Speaker 1: She told me that, you know, if you can do 252 00:15:40,600 --> 00:15:43,560 Speaker 1: organ transplantation, she doesn't know why you can't do gene 253 00:15:43,680 --> 00:15:48,600 Speaker 1: transplantation too. But there have been years of hard work 254 00:15:48,640 --> 00:15:50,840 Speaker 1: and setbacks to get to this point. To be fair, 255 00:15:51,720 --> 00:15:54,240 Speaker 1: there were many gene therapy trials in the decade between 256 00:15:55,560 --> 00:15:58,479 Speaker 1: and two thousand and nine, and about as many failures. 257 00:15:59,200 --> 00:16:02,720 Speaker 1: A young man, Jesse Gelsinger, died in once a trial 258 00:16:02,840 --> 00:16:09,800 Speaker 1: run by a colleague of Kathy's at penn What do 259 00:16:09,840 --> 00:16:13,440 Speaker 1: I remember when I found out about the death of 260 00:16:13,520 --> 00:16:19,880 Speaker 1: Jesse Gelsinger? I do remember Kathy couldn't have known at 261 00:16:19,920 --> 00:16:24,040 Speaker 1: the time, but Jesse's death would upend the gene therapy 262 00:16:24,080 --> 00:16:29,080 Speaker 1: field for a generation. Suddenly investors and pharmaceutical companies didn't 263 00:16:29,120 --> 00:16:34,720 Speaker 1: want to touch this controversial field. Because I had been 264 00:16:34,760 --> 00:16:41,720 Speaker 1: to speak the night before at the Hemophilia Association of 265 00:16:41,760 --> 00:16:46,560 Speaker 1: New Jersey and I had been talking about the work 266 00:16:46,600 --> 00:16:50,200 Speaker 1: that we were doing in gene therapy. And the next morning, 267 00:16:50,760 --> 00:16:54,040 Speaker 1: the director of the hemp Association of New Jersey called 268 00:16:54,080 --> 00:16:59,880 Speaker 1: me because it was in the newspaper. It was a shock. Interesting. 269 00:17:00,720 --> 00:17:02,800 Speaker 1: Jay says he actually takes comfort in the fact that 270 00:17:02,880 --> 00:17:06,760 Speaker 1: SPARK is associated with the University of Pennsylvania, where Jesse died. 271 00:17:07,400 --> 00:17:09,439 Speaker 1: If if there's ever a bunch of people to go with, 272 00:17:09,640 --> 00:17:13,560 Speaker 1: it's the people who um got surprised in the past 273 00:17:13,960 --> 00:17:18,480 Speaker 1: and learned the hardest lessons. The patient's taking part in 274 00:17:18,600 --> 00:17:22,560 Speaker 1: Kathy's gene therapy studies were safe, but for years her 275 00:17:22,600 --> 00:17:26,119 Speaker 1: research kept running into a different problem. The body's natural 276 00:17:26,119 --> 00:17:29,520 Speaker 1: immune system would detect the cells carrying the new genes 277 00:17:29,840 --> 00:17:31,720 Speaker 1: and wipe them out. Why did they do that? Did 278 00:17:31,720 --> 00:17:35,560 Speaker 1: they identify it as a pathogen? Yeah, So what happened 279 00:17:35,600 --> 00:17:37,840 Speaker 1: was that they found out that when you put in 280 00:17:37,920 --> 00:17:42,600 Speaker 1: these virus like particles, maybe unsurprisingly, the body react. When 281 00:17:42,760 --> 00:17:44,560 Speaker 1: we get the flu or we get some other kind 282 00:17:44,560 --> 00:17:47,720 Speaker 1: of virus, our body will respond and it will see 283 00:17:47,760 --> 00:17:51,080 Speaker 1: this as a potential threat. So the immune system came back, 284 00:17:51,240 --> 00:17:54,400 Speaker 1: took out all those cells, left everything alone, else alone, 285 00:17:55,040 --> 00:17:56,560 Speaker 1: and thought, hey, I did a great job on this. 286 00:17:57,280 --> 00:18:00,720 Speaker 1: So it doesn't sound like that's what Kathy was hoping for. No, 287 00:18:01,600 --> 00:18:04,359 Speaker 1: but then there was a breakthrough. Let's go back to 288 00:18:04,400 --> 00:18:06,840 Speaker 1: that doctor in Patro Italy. We heard at the beginning 289 00:18:06,840 --> 00:18:09,919 Speaker 1: of the show. The doctor had found a patient with 290 00:18:09,960 --> 00:18:13,440 Speaker 1: a random mutation in the gene that makes the protein factorne. 291 00:18:14,359 --> 00:18:18,120 Speaker 1: This mutation is really the tiniest change, a single letter 292 00:18:18,160 --> 00:18:22,119 Speaker 1: of the genome mutated changed from a g d n A. 293 00:18:22,800 --> 00:18:26,440 Speaker 1: That tiny change meets factor nine protein way more effective 294 00:18:26,440 --> 00:18:30,040 Speaker 1: than normal. We still don't fully understand why, and that 295 00:18:30,080 --> 00:18:32,520 Speaker 1: sounds like a potential game changer for someone like j 296 00:18:32,720 --> 00:18:36,760 Speaker 1: with hemophilia B because the supercharge protein is more effective 297 00:18:36,760 --> 00:18:39,240 Speaker 1: than normal, you need less of it, and having a 298 00:18:39,320 --> 00:18:44,280 Speaker 1: smaller amount of gene therapy product those little things that 299 00:18:44,320 --> 00:18:47,520 Speaker 1: are derived from viruses entering the body, that means there's 300 00:18:47,600 --> 00:18:50,240 Speaker 1: less chance of triggering the immune system to attack the 301 00:18:50,280 --> 00:18:53,840 Speaker 1: foreign elements, which is what killed the cells in Cathy's 302 00:18:53,880 --> 00:18:56,960 Speaker 1: earlier trials. So I can't wait to hear did it work. 303 00:18:57,440 --> 00:19:00,160 Speaker 1: So far, it's encouraging. Eat. Out of the ten men 304 00:19:00,200 --> 00:19:02,719 Speaker 1: who have been infused in this study have not had 305 00:19:02,760 --> 00:19:06,639 Speaker 1: an immune response, so two of them did. But Spark 306 00:19:06,720 --> 00:19:10,520 Speaker 1: thinks that can basically control that kind of immune response, 307 00:19:10,880 --> 00:19:13,600 Speaker 1: and it's used steroids to try and tamp down the 308 00:19:13,640 --> 00:19:16,440 Speaker 1: body's immune system, which has worked out pretty well for 309 00:19:16,440 --> 00:19:18,840 Speaker 1: at least one of those patients. The other one is 310 00:19:18,880 --> 00:19:26,119 Speaker 1: still producing a pretty steady amount of factor nine. Okay, 311 00:19:26,280 --> 00:19:28,600 Speaker 1: so far we've learned about this new therapy from a 312 00:19:28,600 --> 00:19:32,120 Speaker 1: company called Spark to treat people with hemophilia. We've learned 313 00:19:32,119 --> 00:19:34,840 Speaker 1: it's been pretty effective in the very early tests, and 314 00:19:34,880 --> 00:19:37,640 Speaker 1: it gets around some roadblocks that have held back other 315 00:19:37,680 --> 00:19:42,239 Speaker 1: gene therapies. So, Donnie, what's next so to move the 316 00:19:42,240 --> 00:19:45,800 Speaker 1: therapy to a broader group of patients, Spark and its partner, 317 00:19:46,080 --> 00:19:49,159 Speaker 1: the pharmaceutical giant Fightser will have to test it in 318 00:19:49,240 --> 00:19:52,960 Speaker 1: final stage studies, and they're called Phase three. Sparks CEO 319 00:19:53,080 --> 00:19:56,320 Speaker 1: Jeff Mrazzo says it's now in Fightser's hands as to 320 00:19:56,359 --> 00:20:00,160 Speaker 1: when that trial will begin this quarter. We are also 321 00:20:00,240 --> 00:20:04,680 Speaker 1: conducting a meeting with the FDA under what's called a 322 00:20:04,720 --> 00:20:08,480 Speaker 1: breakthrough Therapy designation, which we received for there are human 323 00:20:08,520 --> 00:20:12,320 Speaker 1: fill a B product candidate UM and those discussions, as 324 00:20:12,359 --> 00:20:16,120 Speaker 1: well as subsequent internal discussions with Fish will that they 325 00:20:16,160 --> 00:20:18,280 Speaker 1: will to me determine what steps they want to take 326 00:20:18,320 --> 00:20:21,320 Speaker 1: for those bigger and longer trials will be necessary to 327 00:20:21,400 --> 00:20:23,800 Speaker 1: make sure that the therapy works on a larger scale, 328 00:20:24,280 --> 00:20:27,640 Speaker 1: that it's safe, and that it will actually continue lasting. 329 00:20:28,080 --> 00:20:30,920 Speaker 1: So this is not a done deal, no, not by 330 00:20:30,920 --> 00:20:34,640 Speaker 1: any means. Tons of therapies that go into these kind 331 00:20:34,640 --> 00:20:38,480 Speaker 1: of trials can still fail to show widespread success or 332 00:20:38,520 --> 00:20:40,280 Speaker 1: there could be some kind of dangerous sun effect that 333 00:20:40,280 --> 00:20:43,360 Speaker 1: didn't show up before. So I'm really curious, Donnie, if 334 00:20:43,359 --> 00:20:46,760 Speaker 1: this shows promise with with hemophilia B as as seems 335 00:20:46,760 --> 00:20:49,439 Speaker 1: to be showing what kind of other diseases can we 336 00:20:49,480 --> 00:20:53,440 Speaker 1: address with gene therapy? Yeah, so Spark is actually working 337 00:20:53,640 --> 00:20:56,320 Speaker 1: right now. They've finished a phase three study looking at 338 00:20:56,320 --> 00:21:00,439 Speaker 1: this rare form of blindness that's caused by a genetic defect, 339 00:21:00,440 --> 00:21:03,680 Speaker 1: and they're actually moving towards trying to get that approved 340 00:21:03,680 --> 00:21:06,199 Speaker 1: by the FDA. And there are other companies that are 341 00:21:06,280 --> 00:21:09,879 Speaker 1: working on things like sickle cell disease. UM, there's a 342 00:21:09,920 --> 00:21:12,560 Speaker 1: small group in China that's working on certain forms of cancer. 343 00:21:12,720 --> 00:21:15,480 Speaker 1: Are there any ethical concerns that have slowed down the 344 00:21:15,520 --> 00:21:19,000 Speaker 1: adoption of these techniques? I mean questions about whether we 345 00:21:19,080 --> 00:21:22,520 Speaker 1: are you know, tinkering with uh, you know, mother nature 346 00:21:22,800 --> 00:21:25,960 Speaker 1: or or the design of our bodies. Well, I think 347 00:21:25,960 --> 00:21:29,399 Speaker 1: in this case, it's not such an ethical concern. For 348 00:21:29,480 --> 00:21:32,040 Speaker 1: one thing, you're not changing people's genes. You're giving them 349 00:21:32,080 --> 00:21:34,160 Speaker 1: a new one, and you're giving them one that will 350 00:21:34,160 --> 00:21:37,200 Speaker 1: help them live just a healthier and better life. And 351 00:21:37,480 --> 00:21:40,120 Speaker 1: in a sense, we're already tinkering with mother nature when 352 00:21:40,119 --> 00:21:42,080 Speaker 1: we're giving people fact or nine, which is part of 353 00:21:42,080 --> 00:21:44,439 Speaker 1: what's keeping them align in the first place. So just 354 00:21:44,480 --> 00:21:47,679 Speaker 1: to be clear, they don't they can't pass on the 355 00:21:47,680 --> 00:21:50,800 Speaker 1: new gene as if it was their their original gene, right, 356 00:21:50,840 --> 00:21:54,879 Speaker 1: they don't. They doesn't. This treatment doesn't change their genetic makeup. Yeah, 357 00:21:54,920 --> 00:21:57,679 Speaker 1: that's right. So the basic idea here is it doesn't incorporate, 358 00:21:57,720 --> 00:22:00,879 Speaker 1: It doesn't get into the the rest of the genome. 359 00:22:01,000 --> 00:22:03,320 Speaker 1: It's not like it's going into any of the cells 360 00:22:03,359 --> 00:22:06,719 Speaker 1: that like sperm or egg that would eventually get passed down. Okay, 361 00:22:06,800 --> 00:22:10,399 Speaker 1: I got it, so um obviously and decrypted. We we 362 00:22:10,480 --> 00:22:14,320 Speaker 1: deal with businesses and the technologies effect on businesses. So 363 00:22:14,600 --> 00:22:19,800 Speaker 1: obviously treating hemophilia is a large lucrative market. What what 364 00:22:19,840 --> 00:22:24,359 Speaker 1: do these gene therapies mean for healthcare and the businesses 365 00:22:24,440 --> 00:22:27,280 Speaker 1: that are pursuing these kinds of cures. There are a 366 00:22:27,359 --> 00:22:31,200 Speaker 1: number of companies like Shire and Nova Nordisk and Fiser itself, 367 00:22:31,320 --> 00:22:34,600 Speaker 1: which makes a ton of money from selling therapies to 368 00:22:34,680 --> 00:22:37,720 Speaker 1: hemophilia patients, and those therapies do a lot of good. 369 00:22:37,760 --> 00:22:39,600 Speaker 1: But of course, if you had a gene therapy that 370 00:22:39,640 --> 00:22:42,639 Speaker 1: would be a one time shot cure, then they would 371 00:22:42,640 --> 00:22:44,920 Speaker 1: be losing a lot of market share. But it's an 372 00:22:44,920 --> 00:22:49,240 Speaker 1: interesting point that they could end up undermining their own businesses. Yeah, 373 00:22:49,240 --> 00:22:51,480 Speaker 1: I mean I think that that's how these companies like 374 00:22:51,520 --> 00:22:53,360 Speaker 1: to think about these things where you know they want 375 00:22:53,400 --> 00:22:55,520 Speaker 1: to make the next generation, and in this case, the 376 00:22:55,560 --> 00:22:59,359 Speaker 1: next generation is really the hope is a one time cure. 377 00:22:59,720 --> 00:23:02,280 Speaker 1: But I think that it's fair to say we're not 378 00:23:02,359 --> 00:23:04,919 Speaker 1: there yet and they're still planning on making billions of 379 00:23:04,960 --> 00:23:07,959 Speaker 1: dollars from hum ahiliate patients for the foreseeable future. Are 380 00:23:08,000 --> 00:23:10,359 Speaker 1: are there any other gene therapies like this that are 381 00:23:10,359 --> 00:23:14,040 Speaker 1: close to being commercialized? Yeah? So pharm a giant Glaxow 382 00:23:14,080 --> 00:23:17,399 Speaker 1: smith Klin actually has a gene therapy on the market 383 00:23:17,440 --> 00:23:20,960 Speaker 1: now in Europe for um a super rare disease called 384 00:23:21,000 --> 00:23:24,040 Speaker 1: bubble boy disease. That's the kind of common name for it. 385 00:23:24,040 --> 00:23:26,119 Speaker 1: It's only approved in Europe and it costs more than 386 00:23:26,119 --> 00:23:29,320 Speaker 1: six thousand dollars. But the idea is that it's a 387 00:23:29,320 --> 00:23:32,760 Speaker 1: one time shot that could replace an enzyme therapy that 388 00:23:32,840 --> 00:23:36,800 Speaker 1: costs like three dollars a year. So how excited should 389 00:23:36,840 --> 00:23:39,480 Speaker 1: we be? Well, I think the science is super cool 390 00:23:39,560 --> 00:23:42,800 Speaker 1: and it's super exciting and we are seeing results, but 391 00:23:42,880 --> 00:23:45,159 Speaker 1: we shouldn't get ahead of ourselves either. We're still in 392 00:23:45,160 --> 00:23:48,040 Speaker 1: the early days here, and even though there is at 393 00:23:48,119 --> 00:23:50,399 Speaker 1: least you know, one patient that's out more than a 394 00:23:50,480 --> 00:23:53,720 Speaker 1: year with this spark gene therapy. That's seeing it work 395 00:23:53,800 --> 00:23:56,159 Speaker 1: for them. We still need to see what the long 396 00:23:56,280 --> 00:23:58,600 Speaker 1: term effects are and how could work in other diseases. 397 00:23:58,880 --> 00:24:02,800 Speaker 1: And I would imagine they're some regulatory hurdles as well. Yeah, 398 00:24:02,840 --> 00:24:05,160 Speaker 1: I mean, of course they're going to have to succeed 399 00:24:05,200 --> 00:24:07,920 Speaker 1: in their final stage study, which is a real difficult 400 00:24:07,960 --> 00:24:10,520 Speaker 1: hurl to get over, and of course when you're working 401 00:24:10,520 --> 00:24:13,520 Speaker 1: with regulators, you know there's a big process ahead of them. 402 00:24:13,840 --> 00:24:16,320 Speaker 1: But the hope is that for a rare disease, those 403 00:24:16,359 --> 00:24:18,520 Speaker 1: things can move quickly and if they really prove that 404 00:24:18,560 --> 00:24:23,280 Speaker 1: they work, that this thing can move forward before we 405 00:24:23,320 --> 00:24:25,320 Speaker 1: wrap up or show today. What are Jay and his 406 00:24:25,400 --> 00:24:28,200 Speaker 1: wife you Alanta, up to now? So when I met 407 00:24:28,240 --> 00:24:31,160 Speaker 1: them in Philadelphia, Jay was about to have his appointment. 408 00:24:31,160 --> 00:24:33,680 Speaker 1: He was going to find out how much factor nine 409 00:24:34,040 --> 00:24:36,760 Speaker 1: was actually being active in his body, and they found 410 00:24:36,800 --> 00:24:41,119 Speaker 1: out the next day that he had normal factor nine activity, 411 00:24:41,160 --> 00:24:43,840 Speaker 1: which maybe doesn't sound great, but for someone like Jay, 412 00:24:43,880 --> 00:24:46,320 Speaker 1: that's pretty amazing, and that's somewhere where you can really 413 00:24:46,320 --> 00:24:49,920 Speaker 1: have a basically completely normal life. And it's showing. I mean, 414 00:24:50,160 --> 00:24:53,080 Speaker 1: they're feeling a lot more free and Jay even feels 415 00:24:53,080 --> 00:24:57,200 Speaker 1: a little reckless. Here's his wife Filanta, Because we always 416 00:24:57,200 --> 00:25:00,359 Speaker 1: traveled with the with the package with the act or 417 00:25:00,440 --> 00:25:04,600 Speaker 1: nine just in case if something happens every time when 418 00:25:04,600 --> 00:25:08,400 Speaker 1: we were traveling, and this time it was the first 419 00:25:08,440 --> 00:25:11,560 Speaker 1: time when he said maybe I should not take it. 420 00:25:12,840 --> 00:25:17,320 Speaker 1: That's a huge change. That's like hundred eighty degree change 421 00:25:18,160 --> 00:25:23,359 Speaker 1: degrees change in his behavior by saying that it's generally stupid. 422 00:25:23,440 --> 00:25:26,400 Speaker 1: But we only have so much space in our luggage. 423 00:25:26,400 --> 00:25:28,719 Speaker 1: So I was thinking, well, if we're going to New 424 00:25:28,800 --> 00:25:30,560 Speaker 1: York in a few days, maybe you wanted to need 425 00:25:30,600 --> 00:25:36,800 Speaker 1: some more space for her shopping. And from scientific point 426 00:25:36,840 --> 00:25:41,159 Speaker 1: of view, yes, definitely, it was interesting. It was something 427 00:25:41,640 --> 00:25:44,400 Speaker 1: and I said, okay, I have a GMO husband now. 428 00:26:07,800 --> 00:26:10,720 Speaker 1: And that's it for this week's episode of Decrypted. Thanks 429 00:26:10,760 --> 00:26:13,040 Speaker 1: for listening. We love to hear what you thought of 430 00:26:13,080 --> 00:26:15,639 Speaker 1: this episode. Record a voice message and send it to 431 00:26:15,680 --> 00:26:18,840 Speaker 1: us at Decrypted at Bloomberg dot net or I'm on 432 00:26:18,880 --> 00:26:22,239 Speaker 1: Twitter at Donnie Bloomfield and I'm at brad Stone. If 433 00:26:22,280 --> 00:26:25,520 Speaker 1: you haven't already, please subscribe to our show on iTunes 434 00:26:25,640 --> 00:26:28,080 Speaker 1: or wherever you get your podcasts and leave us a 435 00:26:28,200 --> 00:26:31,600 Speaker 1: rating and a review. It really helps more listeners Finder show. 436 00:26:32,440 --> 00:26:36,040 Speaker 1: This episode was produced by Pio Gukari, Liz Smith, and 437 00:26:36,200 --> 00:26:39,399 Speaker 1: Magnus and Rickson. A special thanks to our reporter Shelley 438 00:26:39,440 --> 00:26:42,560 Speaker 1: Hagen for help with today's show. Alc McCabe is head 439 00:26:42,640 --> 00:26:47,960 Speaker 1: of Bloomberg Podcast. We'll see you next week.