With little fanfare, Anthony Letai, a highly respected physician-scientist, was sworn in as the 18th director of the National Cancer Institute on Sept. 29. Then, two days later, on Oct. 1, the government shut down.
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The news of Letai’s apparent appointment was broken last week in the media, with no word from the White House. Although HHS has published a press release announcing Letai’s appointment, the White House is still silent on the matter.
Meanwhile, Trump’s FDA initiated an unusual regulatory pathway for leucovorin—asking the drug sponsor to reinstate a 25-year-old drug application—in order to begin the process of approving the drug for autism.
This week on The Cancer Letter Podcast, Paul Goldberg, editor and publisher of The Cancer Letter, and Jacquelyn Cobb, associate editor, discuss the oncology community’s enthusiastic support for Letai’s appointment, the government shutdown, and the strange regulatory future of leucovorin.
“Here’s the issue,” Paul said. “Leucovorin is a branded drug up through about 1997. By 1997, the company asks to just let it go to the generics. ‘The heck with this thing.’ Then, by 1999—GSK is the sponsor—GSK just withdraws from the whole thing, which makes perfect sense. That’s what pioneer companies do, because who wants to be updating the label on something you’re not selling? Who wants to be responsible for that? So, that’s just typical behavior.
“So, a quarter of a century ago. Now, fast forward to now and 26 years later, really, and there’s this sort of a political push, not necessarily scientific, but maybe a little so, to get this thing approved for autism, for a form of autism. So, the only reason to get that approval is so you can start promoting it.
“So, really, probably for the first time in the history of FDA and therefore likely for the first time in human history, the company was allowed, or in this case, really probably prevailed upon, to renew, revive, its NDA, and then seek a supplemental NDA for this indication.”
Stories mentioned in this podcast include:
- Anthony G. Letai to be named NCI director. The Dana-Farber and Harvard physician-scientist is an inspired choice, colleagues say
- Trump’s FDA invents an unusual regulatory pathway to approve leucovorin for autism. Experts call the move “extremely premature”
- Population-based cancer surveillance is a national treasure at risk, by Eric B. Durbin, Karen L. Knight, Betsy Kohler, and Sarah Nash
- Ci4CC’s 24th Symposium & Workshop set to focus on precision oncology powered by data intelligence, by Stephen D. Nimer
- Earlier diagnosis, better outcomes: Telemedicine has found a home in oncology, by Hardeep Phull
- Championing nurse wellbeing as a strategic priority, by Kim Slusser
This episode was transcribed using AI transcription services. It has been reviewed by our editorial staff, but the transcript may be imperfect.
The following is a transcript of this week’s In the Headlines, a weekly series on The Cancer Letter Podcast:
Jacquelyn Cobb (00:00): This week on The Cancer Letter Podcast…
Paul Goldberg (00:05): Anthony Letai, from a place called Harvard. Have you heard of it?
Jacquelyn Cobb (00:10): Yeah. It’s like off the beaten path, kind of not well known. It’s, yeah, I’ve heard it’s good though.
Paul Goldberg (00:16): Yeah. It’s in Boston. It’s,
Jacquelyn Cobb (00:18): It’s in Cambridge, actually.
Paul Goldberg (00:20): Well, Boston area. So, but, but seriously I don’t think anyone I know has anything but good things to say about him. So, the 18th NCI director, I called a bunch of people who knew him and who know him, rather, it’s present tense, and they all had wonderful things to say.
Before we list the names. I think we should probably talk a little bit more about the timing. ’cause he was sworn in by Kennedy on September 29th and actually we knew about this happening for maybe three weeks. And we didn’t break the story deliberately because we were actually hoping, you know, to be able to say that he was actually named, because there was—
Jacquelyn Cobb (01:16): Yeah.
Paul Goldberg (01:17): You know, you remember there were a lot of names floating about.
Jacquelyn Cobb (01:21): Yeah. Yeah.
Paul Goldberg (01:21): Some good, some not so good.
Jacquelyn Cobb (01:24): Mm-hmm.
Paul Goldberg (01:25): Some mainstream, some so out of mainstream, and painful to even imagine what could have happened.
You are listening to the Cancer Letter podcast. The Cancer Letter is a weekly independent magazine covering oncology since 1973. I’m your host, Paul Goldberg, editor and publisher of The Cancer Letter.
Jacquelyn Cobb (01:56): And I’m your host, Jacqueline Cobb, associate editor of The Cancer Letter. We’ll be bringing you the latest stories, groundbreaking research and critical conversations shaping oncology.
Paul Goldberg (02:06): So, let’s get going.
Jacquelyn Cobb (02:16): Hey, Paul. How’s it going?
Paul Goldberg (02:18): Hi, Jacquelyn. How are you?
Jacquelyn Cobb (02:21): I am good. I had maybe the best weekend of my life. My I was, I got engaged two weekends ago, which maybe should be the best weekend of my life. But this weekend Kevin, my fiance, invited like all of my childhood friends to come surprise me this weekend. So, from like, New Jersey, from Philadelphia, from Washington DC—they all came up this weekend. And it was just like surprise after surprise after surprise. So it was like, I’m on, I’m on cloud nine.
So, I’m great!
How are you, Paul?
Paul Goldberg (02:54): Mazel Tov! As we say in French.
Jacquelyn Cobb (02:57): Thank you! Yes. Awesome. Thank you, Paul.
Paul Goldberg (03:02): Yeah, this is fantastic.
Jacquelyn Cobb (03:04): Yes, yes.
Paul Goldberg (03:04): You didn’t really reveal those details, but you were proposed to in Stowe, Vermont, they tell me…
Jacquelyn Cobb (03:10): Yes. Yes. That happened. Yeah. It was on a run. It was very on brand for me and my partner. We were—which also, it’s a very high, very eventful time in my life right now. I have my first marathon next weekend too, so I’ll check in about that next week. But yeah, Stowe,Vermont and right on the Von Trapp Family Lodge grounds. So, it was really, really beautiful. And the foliage was like very early peak season this year. So it was just stunning. It was amazing. So beautiful.
Let me take us through this week’s headlines, because I can’t have this be, you know, five minutes of just me talking about my, my life, even though it’s very exciting.
So we have a new NCI director. It’s official. Do you wanna talk a little bit about that, Paul?
Paul Goldberg (03:56): Yep. Anthony Letai from a place called Harvard. Have you heard of it?
Jacquelyn Cobb (04:02): Yeah. It’s like an off the beaten path, kind of not well known. It’s, yeah, I’ve heard it’s good though.
Paul Goldberg (04:08): Yeah. It’s in Boston. It’s a, it’s, it’s been around.
Jacquelyn Cobb (04:10): It’s in Cambridge, actually.
Paul Goldberg (04:12): Well, Boston area.
So, but, but seriously I don’t think anyone I know has anything but good things to say about him. So, the 18th NCI director, I called a bunch of people who knew him and who know him, rather. It’s present tense, and they all had wonderful things to say.
Before we list the names. I think we should probably talk a little bit more about the timing, because he was sworn in by Kennedy on September 29th and actually we knew about this happening for maybe three weeks. And we didn’t break the story, deliberately, because we were actually hoping, you know, to be able to say that he was actually named, because there was, you remember, there were a lot of names floating about.
Jacquelyn Cobb (05:12): Yeah, yeah.
Paul Goldberg (05:13): Some good, some not so good.
Jacquelyn Cobb (05:16): Mm-hmm.
Paul Goldberg (05:17): Some mainstream, some so out of mainstream, it’s painful to even imagine what could have happened. My gosh. But, you know this is very mainstream. Cutting edge is actually a better word for it, so that maybe not be mainstream.
Jacquelyn Cobb (05:35): Yeah.
Paul Goldberg (05:35): So, yeah. So yeah. So, but it’s interesting. He got sworn in and now on Wednesday, October 1st, as we’re taping this, the government has been shut down. So it’s kind of like, hurry up and wait.
Jacquelyn Cobb (05:54): Mm-hmm.
Paul Goldberg (05:55): We don’t know how long this is going to take.
Jacquelyn Cobb (05:57): A whole two days off of work before the current shutdown. It’s very unfortunate that he’s walking into that.
Paul Goldberg (06:05): Yeah. We actually—one thing about the shutdown is that we actually do not know how NCI is planning to get through it, because in the past we kind of knew it.
There was, you know, there was a memo that came out first. This is priority one. This is priority two. I haven’t seen anything yet. I have no idea. I mean, I hope all the animals stay alive. I know, I’m sure everything will be fine. It’s just sort of not clear what the process is. ’cause NCI is a tough and resilient place, and they’ll get through it.
Jacquelyn Cobb (06:45): Mm-hmm.
Paul Goldberg (06:47): I hope But can we—let’s talk about Letai for a few minutes.
Jacquelyn Cobb (06:53): Yeah, yeah, totally. He is a functional diagnostics expert. I think that’s what you’re referring to when you said cutting edge. He focuses on apoptosis and he has focused specifically on BCL2. It’s a pathway that I am not familiar with, so I’m not gonna get into the details of it. But it led to the BCL2 two inhibitor drug, Venclexta or Venetoclax… Always tongue twisters with these drug names.
But yeah. So, he’s, like you said, Paul, he is incredibly well respected by former NCI directors, former NIH directors. Monica Bertagnolli talked about how he’s an outstanding clinician scientist. We have Kim Rathmell supporting him, Ned Sharpless, Bill Kaelin—the Nobel Laureate also from Harvard. Brian Drucker from OHSU and Bruce Rabner. So a lot of a lot of support.
Paul Goldberg (08:07): And, you know, I could have contacted 10 more people and gotten 10 more things, 10 more really topnotch people everybody respects.
Jacquelyn Cobb (08:16): Yeah.
Paul Goldberg (08:16): And would’ve gotten a lot of, more and more, I just had to stop somewhere.
Jacquelyn Cobb (08:20): Yeah. Yeah. I haven’t heard anybody say anything negative about him.
Paul Goldberg (08:25): Yeah. Not even, not even in a way that would be well, you gotta watch out for blah, blah, blah, whatever. No, no, no, no, no. This is all good.
Jacquelyn Cobb (08:34): Yeah.
Paul Goldberg (08:35): So, I mean, this is a guy who would’ve been a great hire for any administration.
Jacquelyn Cobb (08:44): Yeah.
Paul Goldberg (08:47): Yeah, it’s an interesting, interesting thing.
I’m really looking forward to seeing him come in and stabilize the place. And I’m sure that their morale is not great. And I know morale is not great, and I’m also sure that it’s not gonna get better as a result of the shutdown.
Jacquelyn Cobb (09:10): Yeah. Yep. Yep. Absolutely. Well, at least we have this one sort of spot of, of hope and stability and, you know, like Dr. Kaelin said—I love this, I don’t know why it resonates with me so much, but Dr. Kaelin called Letai “a refreshingly well-qualified choice.” So, we have good leadership!
Paul Goldberg (09:33): Yeah. Yeah. It really is. It really is the case. But, you know, you can’t just say that it’s one thing. It’s one in a series of good news of good—of events that really are positive for NIH and NCI, the House and Senate bill.
Jacquelyn Cobb (09:55): I mean, that’s, it’s better than the catastrophic news of the budget, but it’s still not like good news. I feel like any other year we’d be like, oh, flat funding. No, that’s, you know, like, it’s still, you know,
Paul Goldberg (10:08): Well, it’s sort of like commutation of a death sentence.
Jacquelyn Cobb (10:11): Yeah.
Paul Goldberg (10:11): Yes. Or near that, which is what the president’s budget proposal was. It wasn’t quite a death sentence, but functionally it kind of was.
Jacquelyn Cobb (10:20): Yeah.
Paul Goldberg (10:21): And then there’s, there’s a lot—but, you know, that’s not where we are, so forget it. I think it’s good to see those things happen better than them not happening. And this guy is a great hire for any administration.
And in fact, I kind of missed the time when NCI directors could go from administration to administration, and nobody really cared because NCI is NCI science and is science, and there’s no, there’s no party affiliation issues. Or shouldn’t be.
Jacquelyn Cobb (10:59): Yeah.
Paul Goldberg (11:00): And I would hope that he sticks around for several administrations. That would be, that would be ideal. So, good news.
Jacquelyn Cobb (11:12): Good news.
Claire and Paul worked on a very, very, very complicated regulatory story about Trump’s FDA inventing a wonky pathway, basically with the aim of approving leucovorin for the treatment of autism. And leucovorin, it’s not a chemotherapy, but it’s given alongside chemotherapy. Often, that’s its main use at this point.
We had three guest editorials this week. One was about the importance of continued federal funding for the North American Cancer Surveillance Enterprise. That is an excellent guest editorial. Definitely recommend checking that out. I say that every week, but this one is for real. The second was about the role of telemedicine in oncology, and the third was a case study. MD Anderson has a case study about how to successfully prioritize the well-being of nurses at academic cancer centers and how that is to the benefit of patients and nurses alike.
Do you want to talk about the story two a little bit? I know it is quite complicated, but we can do just a little chat about it. I thought it was really fascinating, the leucovorin story.
Paul Goldberg (12:17): Yeah, that one was really kind of a doozy, because FDA, and I suspect it had something to do with Kennedy as well, got very excited about the possibility of leucovorin being an effective treatment for autism for some forms of autism.
And yeah, a lot of excitement, data are a little on the thin side, not what you usually see to approve drugs. Although sometimes with rare diseases in pediatrics, for example, you do see pretty thin data packages for approval. So, let’s be fair here.
But then comes the really interesting part is the pathway they chose, because leucovorin is a very old drug and it’s used with 5-FU and methotrexate. That gives you an idea right there. I’m actually old enough to remember… Well, just after—
Jacquelyn Cobb (13:16): No, I want to know. Please, please.
Paul Goldberg (13:40): Well, I just remember when there was discussion of leucovorin versus levamisole and with 5-FU, and we really have no idea. Levamisole really didn’t work. And it’s just a fascinating story of levamisole, which is such a tangent. Do you want me to keep going on the tangent?
Jacquelyn Cobb (13:57): I do. Personally, I do.
Paul Goldberg (14:01): The beauty of levamisole in colon cancer was that it basically showed in early studies—and there weren’t late studies—that there was some efficacy. However, the efficacy was due to the fact that 5-FU was being administered on a schedule.
So, it’s like you do better on a clinical trial than in reality in the world. So, in this case, it was because it was just… They weren’t playing every which way with the dose and—
Jacquelyn Cobb (14:41): Oh my gosh.
Paul Goldberg (14:42): Yeah. Yeah. So, that’s what it showed. And then later studies showed that it was completely ineffective, and it was replaced. And it was a great story because you could buy, and this is a Chuck Mortel story from Mayo. Chuck Mortel discovered that you could buy very, very cheap animal-grade levamisole as opposed to human levamisole; it’s the same drug, but levamisole had nothing to do with it. It was replaced by leucovorin.
So, we’re talking really old stuff, and I was there. Oh boy. Yeah, I’m also exactly as old as 5-FU, by the way.
Jacquelyn Cobb (15:30): How did I not know that?
Paul Goldberg (15:31): I don’t know.
Jacquelyn Cobb (15:32): That’s crazy.
Paul Goldberg (15:33): I just looked it up, and I don’t know that speak volumes for my mental health that I looked up my age versus the age of 5-FU.
So, anyway, enough of the detours. These are not just detours. This is not good. Yeah
Jacquelyn Cobb (15:40): I’m having a good time.
Paul Goldberg (15:50): I don’t think anybody else is, but…
Jacquelyn Cobb (16:00): You are, that’s for sure.
Paul Goldberg (16:01): No, I am. I am. But hey, I could just be sitting there without wasting time with people who are watching or not watching this. So, where were we? Oh, yeah, yeah, yeah, yeah. Leucovorin.
All right. Here’s the issue. Leucovorin is a branded drug up through about 1997. By 1997, the company asks to just let it go to the generics. ‘The heck with this thing.’ Then, by 1999—GSK is the sponsor—GSK just withdraws from the whole thing, which makes perfect sense. That’s what pioneer companies do, because who wants to be updating the label on something you’re not selling? Who wants to be responsible for that? So, that’s just typical behavior.
So, a quarter of a century ago. Now, fast forward to now and 26 years later, really, and there’s this sort of a political push, not necessarily scientific, but maybe a little so, to get this thing approved for autism, for a form of autism.
Jacquelyn Cobb (17:25): Yeah, it’s CFD, it’s cerebral folate deficiency, which I think people with CFD demonstrate autistic features. It’s a related condition, it’s not quite, but I think the administration definitely has its eyes set or its aim set on having leucovorin approved for autism eventually, but that’s just not where they’re at right this second.
Paul Goldberg (17:49): So, the only reason to get that approval is so you can start promoting it.
So if you go to an SNDA approach, but to have an SNDA, you have to have an active NDA. And in this case, GSK gave up its NDA 26 years ago. So, really, probably for the first time in the history of FDA and therefore likely for the first time in human history, the company was allowed, or in this case, really probably prevailed upon, to renew, revive, its NDA, and then seek a supplemental NDA for this indication.
Now, the company is not going to be going back into the sort of big market for leucovorin.
Jacquelyn Cobb (18:58): Yeah.
Paul Goldberg (18:59): There’s no way.
Jacquelyn Cobb (19:00): Yeah.
Paul Goldberg (19:01): It’s just going to open that up and make it available and let them have it, and I guess it’s just an odd story. Plus they actually even kept the same NDA number as they had before and some folks have been pointing out that as a result of the drug shortages, which by the way also affected leucovorin in a pretty major way, which was catastrophic during the drug shortages, or as a result of the drug shortages, FDA got the authority to approve drugs, cancer drugs, and this is a cancer adjacent drug and they could have done that. They could have really done that without GSK, but they chose to do it through GSK. Maybe it’s a path of least resistance.
Jacquelyn Cobb (19:53): So you said that this was the first time in human history, but that’s specifically the FDA is asking a company to resubmit an NDA that is long—
Paul Goldberg (20:05): To revive an old NDA and do so under the same number. So suddenly it’s as though those 26 years never passed, which is, I mean, you have to be a certain kind of nerd to be very interested in this.
Jacquelyn Cobb (20:23): I know, I was just gonna say that.
Paul Goldberg (20:25): We at The Cancer Letter are precisely that kind of nerds.
Jacquelyn Cobb (20:28): Yeah. I was literally gonna say we’re regulatory nerds. It’s fascinating to me.
Paul Goldberg (20:32): Yeah. What a story. It’s a really… You kind of have to think of Hatch-Waxman and how that works and why do the company… Anyway, but it was really a lot of fun, and it was actually a very important story to have to actually report in this way. So this was a fun issue for all of us.
Jacquelyn Cobb (20:57): Absolutely. Yeah.
Paul Goldberg (20:59): Yeah. I got to kind of report around the edges. Claire did a beautiful job on the FDA story and, of course, on the NCI story, and I’ve been sniffing around on the edges of the story and trying to bring in the parts that Claire didn’t or couldn’t really, or could, but couldn’t be expected—
Jacquelyn Cobb (21:24): I don’t think she’d be mad about that. Yeah, I think she would say the same thing.
Paul Goldberg (21:26): No, no, no, no, no. It is kind of perfect because I was doing the work that I couldn’t do.
Jacquelyn Cobb (21:32): Yeah, exactly.
Paul Goldberg (21:33): Yeah.
Jacquelyn Cobb (21:34): It’s awesome. Well, beautiful, beautiful week last week. Very nice and a fun podcast. I had a good time. It might be a little tangential for the general audience, but…
Paul Goldberg (21:45): I hope others listen to it, and then I hope there are people still out there who care about levamisole as much as I do.
Jacquelyn Cobb (21:56): Yeah, I bet they’re out there for you, Paul. All right, well, thank you so much. I will talk to you next week.
Paul Goldberg (22:02): Alright, thank you. All right. Bye-bye.
Jacquelyn Cobb (22:06): Thank you for joining us on The Cancer Letter Podcast, where we explore the stories shaping the future of oncology. For more in-depth reporting and analysis, visit us at cancerletter.com. With over 200 site license subscriptions, you may already have access through your workplace. If you found this episode valuable, don’t forget to subscribe, rate and share together, we’ll keep the conversation going.
Paul Goldberg (22:27): Until next time, stay informed, stay engaged, and thank you for listening.
