Clinical Efficacy and Future Prevention Trials

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He also addresses the dangers of irrational beliefs and the risks of applying astrology to serious decisions Wide ranging and entertaining, What Science Says about astrology is the first book in the new What Science says series. Available now wherever books are sold, WNYC Studios is supported by the New York Hall of Science, a hands on science center and learning lab in Queens, welcoming New Yorkers to explore, play, watch the World Cup, and more Tickets at nyscI. org. Hi, this is Ira Flato, and you're listening to Science Friday. Pancreatic cancer is among the most deadly forms of cancer and can be difficult to catch early But there is some good news. A new drug called Derexonacib which just finished its clinical trials, had some really promising results. And while it's not a cure, some oncologists are calling it a game changer notot just for pancorereatic cancer, potentially for other forms of cancer too Dr. Ze Wayneberg led a clinical trial for the drug and is the co director of UCLA Health GI oncology program He joins us from Los Angeles Welcome to Science Friday. Thank you, Iirraa. Happy to be here Nice to have you. Okay, first, tell us what this drug did, Just how effective was it for patients with pancreatic cancer Right. So this is a big moment for us because this is a drug that targets The dominant onkg gene in cancer, but especially dominant in pancreatic cancer. and that's called K RAS. and U This trial has gone through several studies over the last, I'd say, four or five years. in a fairly accelerated timeline. initially showing that even an advanced, very advanced pancreatic cancer for which the usual treatments are very short lived This drug producing response rates. It was shrinking tumors. It was making people live longer than we ever could have expected And when we saw that, the company and the investigators quickly moved to accelerate a randomized phase three trial in the same patient population, advanced pancreatic cancer patients, who had already gone through some chemo and randomize them. have got different chemotherapy regimen than they might have received before, which was the standard of care. versus this pill And it fundamentally showed a dramatic improvement in Both the ability to shrink tumors bothoth the ability to have cancer be controlled for a prolonged period of time and it doubled the survival of that group of patients compared to chemotherpeila So in the oncology world, the world of cancer, just how big a deal is this drug? I think Every cancer U, you know, has its moment, so to speak We saw that targeted therapy and breast cancer about thirty years ago We saw that with immunotherapy across the board in melanoma and lung cancers about ten or fifteen years ago. We've never had a moment quite like this. I've done a lot of studies I run pancreatic cancer And most of them have failed. and if they didn't fail, they showed very marginal benefits. So in my opinion, it is a breakthrough moment in the history of pancreatic cancer What is it about this drug that might make it useful for treating other types of cancer So so this Okagene, which is called Kas is the dominant oncogene across all cancers, which means that it's mutated and altered and up to twenty five percent of all cancers That's led by pancreatic cancer in which it's dominated in ninety percent of cases. I think pancreatic cancer is one of these cancers that we all recognize, we don't know a lot. We don't understand. whyy do people get it? Why does it grow so quickly U what We know, though, is that this Anka Jan Kayas is the driving engine behind a lot of the growth of these pancreatic cancers So People have been interested in blocking this and figuring out drugs to walk this gene for about fifty to sixty years, it's gone through a huge Um I would say series of mainly downs, not ups and trying to find drugs that effectively block this cham. U And so this is one of the first but Probably not the only drug that is hitting that threshold of successfully blocking that gene at the source. and effectively decreasing the cascade of signaling that runs through KRS Has it shown effectiveness in other types of cancers yet So it's being studied actively in lung cancer And in colon cancer, mainly in combinations in colorectal cancer, which Corectal cancer also has KRAS mutated about forty percent of the time one cancer about twenty five, thirty percent of the time We can say somewhat convincingly, doesn't work in the same manner And by that, I mean Probably not as good as a single agent in some of these cancers as it has been in pancreatic cancer And one of the hypotheses behind that is that the KRS onkagene while extraordinarily common across a lot of cancers may just be a more important driving engine in certain cancers rather than others. Let's talk about patience because we know because of our audience. They're going to hear about this and want to know when they can get it. So give us an idea of how soon patients might receive this new drug Well, we can say that this is under review by the FDA. Our hope and expectation is that review is very quick Um, and drug will receive forull approval It's hard to know the timelines of that, but obviously, u I think we've concluded this study quite successfully and shown a fairly definitive result. so That's not always the case in oncology drugs. Here it is, in my opinions What's it been like to see these kinds of positive results for patients as you ran the clinical trials because people with advanced pancreatic cancer really have Ver short life expectancies, don't they? Yes. And really in this study We tested it in those with the worst life expectancies, quite frankly, in the patients who had already received chemotherapy So we knew Unfortunately that chemotherapy is going to have a very limited success in that patient population It was very emotional in a challenging way. First of all We did not know that this drug would perform as well U until we saw the results But we did know that it was doing something. and u became challenging for many of us to enroll patients in chemotherapy which was necessary to preserve the randomized study And ultimately, when you see a drug, a pill Turn someone's cancer around and pancreatic cancer. If you ask many of us five years ago, we never would have thought this would have been possible If the drug gets approval from the FDA, would this then become front line treatment for pancreatic cancer Or would patients need to try chemo first So it's hard to say what the FDA will do exactly U But I think our vision is, you know, this is a stepping stone We're doing the other studies as we speak. We're even testing this drug and others In earlier lines of pancreatic cancer, those who had surgery and are unfortunately, very likely to reccur after surgery But we're testing the drug there We're making efforts to test this drug and others like it before surgery. The emphasis now is beyond this immediate second line indication, which just became public. We're already moving three steps ahead trying to get a better handle on the disease by using this drug and others even before it becomes advanced W to thank you for taking time to be with us and good luck with it. Thanks, Iyra. It's been great to chat with you today Dr. Ze Weinberg is the co director of UCLA Health GI, I'm Coeology Program based in Los Angeles, California After the break, another story of a promising drug. This one is for ALS. Stay with us WNYC Studios is supported by the New York Community Trust, providing a powerful way to make a difference on the causes and communities you care about Here's an audio portrait of Nancy Talbot who has a donor advised fund with her husband Jay and is part of a women's giving circle at the Trust I'm a native New Yorker who spent most of my adult life in Chicago. and when we moved back here twenty years ago We looked for a way to reconnect with the city New York Community Trust was our first stop and they introduced us to a Donor Circle, which has enabled me to meet extraordinary heroes in five boroughs who have marvelous ideas but few resources to to make it happen. and we've had the privilege over the years of supporting them in their dreams. 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And you're probably relying on air conditioning to keep cool But if your AC is always turned up Well, your energy bills are likely to go up too Luckily, Con Edison has ways to help Try their energy saving tips, which are personalized to you, or explore budget billing, which helps you spread your biggest payments out across the year Visit coned. com slash Bill helpelp to get started because taking control is New York ALS is a degenerative and ultimately deadly disease. Patients lose their ability to walk, swallow, and eventually breathe But now there's a drug for a rare genetic form of ALS able to stop or even reverse some of these symptoms. My next guest, Pam Bellk A health and science reporter for the New York Times in New York reported on this development. Pam, welcome back to Science Friday Thank you so much Tell us about this drug Tfersin. How does it work Who is it for? Yeah, it is for a genetically caused version of ALS. So about ten percent of ALS cases are caused by known genetic mutations. The rest of the cases, we don't really know the cause But about two percent of ALS cases are caused by a mutation on the SOD one protein And this often causes a particularly aggressive form of ALS people decline very rapidly. And the patients that I focused on in this story, some of them had lost multiple family members over generations. So then we're very hopeful about this drug. Tell us how effffective it is So it's a sort of synthetic drug. and what it does is it binds to a mutated form of RNA on SOD one genes What that does is it stops a toxic form of SOD one protein from being produced. And that's the protein that causes ALS or worsens ALS for sure in these patients. It's actually sort of the first disease modifying therapy that's been approved for ALS, which is pretty huge. As you note, patients die within a few years, typically Almost nobody stabilizes or even improves And when this drug was approved, In twenty twenty three, it was given kind of a conditional approval called accelerated approval because it hadn't actually been shown to be effective. It had been shown to reduce the protein, but they weren't able to show that it worked better than placebo. but As time has played out and people have been followed for several years on this drug. They have found that about twenty five percent of the patients who have received it have either stabilized or improved, which is just does not happen in ALS. And when we're talking about improvement, we're talking about things like Their muscles have gotten stronger. They've been able to maybe walk better. and crucially, for several of them, their breathing scores have improved to the point where maybe they don't need a portable ventilator as much And that is really extraordinary in the world of ALS Yeah, it must have been incredible for them, I mean, to see their own improvements. What were their experiences like? Yeah. I mean The other thing that has just been extraordinary here is that people are alive Right? So many of them expected not to be alive, based on their family history, based on how they were progressing. So the main patient that I focused on in my piece, Amanda Sifford beforefore she started on toophersin three years ago, she was really, as her doctors told me, you know, kind of falling off a cliff in terms of her breathing She had gone from about eighty six percent on a test of breathing function to forty eight percent. And they really thought that she would have maybe a matter of months or a year left live. And three years later, she scored a sixty three percent So that is about the range for somebody who has kind of chronic asthma. So of course, it's not perfect, but it's much more functional for her. She's been able to go dancing No kidding. herer Yeah, you know, she loves to dance that she hadn't been able to do it for years. And this is a woman who's fifty eight, you know, one of the tragedies of ALS is very often strikes people in the prime of their lives. And these kinds of improvements in function can be just really dramatic.