Last week, Richard Pazdur was named to the position of director of FDA’s Center for Drug Evaluation and Research. Much has been written about how Pazdur, with nearly a three-decade long career at the agency, represents a stabilizing choice for FDA as it faces inner and outer turmoil.
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Indeed, on this week’s episode of In the Headlines, we bring you the full audio of a conversation originally published in print in last week’s issue of The Cancer Letter between Ellen Sigal, chair and founder of Friends of Cancer Research, and Karen Knudsen, CEO of the Parker Institute for Immunotherapy, about how Pazdur is a great choice for the position—and the agency.
“We’re not gushers,” Sigal said. “That’s what’s so funny about this. All of us can be quite critical.”
“Now we know, the three of us can gush. We’ve proven ourselves capable,” Knudsen said.
An important piece of this conversation that has not been highlighted elsewhere is the role of Pazdur’s late wife, Mary, in his personal and professional success.
“She was his rock. She was his conscience, she was able to work with him, understand him, guide him, and for sure tell him when he was wrong,” Sigal said. “That ability to have someone you trust that isn’t just admiring you, that is your partner and your best friend and the trust that he had, and Mary would always speak her mind.
“I admired that woman so much. She was just a gift from heaven. I don’t know how, tears come to my eyes when I think of her right now. She was extraordinary, and I think she helped him, and we need to give her the credit for what Rick became.”
In death, Mary Pazdur continued to inform Rick’s work as a patient-oriented regulator.
“He knows personal loss. He knows what it means. He’s very empathetic to patients and the real-world patient that is struggling every single day,” Sigal said. “Every decision is never going to be exact, and he has to be able to take risks, and he understands those that are important to patients. We can’t ever forget in the back of his mind—not only what he went through, but he understands this instinctively—that he’s protecting and helping patients.”
Stories mentioned in this podcast include:
- Richard Pazdur, a respected insider with a plan to reengineer FDA, steps in as CDER director
- Rick Pazdur’s CDER appointment comes at exactly the right moment for FDA
- FDA to remove black box warnings on hormone therapy for menopause
- Smoldering multiple myeloma: Rethinking the waiting game
This episode was transcribed using 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: We have a very special episode for you today. Last week, Paul interviewed Ellen Sigal, the Chairperson and Founder of Friends of Cancer Research, and Karen Knudsen, CEO of the Parker Institute for Cancer Immunotherapy, about Richard Pazdur taking the job of Director of FDA Center for Drug Evaluation and Research. That story was on the cover of last week’s issue, but the conversation between Paul, Sigal, and Knudsen was so good we wanted to share the full thing with our listeners.
Before we jump in, I’ll give you a short overview of the rest of last week’s issue. Ellen Sigal also wrote a guest editorial for us about Pazdur’s appointment to CDER, coming at the perfect time for a very tumultuous FDA.
Claire wrote a story about FDA removing the black box warning on hormone replacement therapy for menopause.
And C. Ola Landgren from Sylvester Cancer Institute wrote a guest editorial about the implications of a recent approval of Daratumumab for high-risk smoldering multiple myeloma, an indication that historically was treated as a watch and wait disease. With that, I’ll hand over the mic to Paul, Sigal, and Knudsen. Enjoy.
Paul Goldberg: With us today we have Ellen Sigal, chair and founder of Friends of Cancer Research; and Karen Knudsen, CEO of Parker Institute for Cancer Immunotherapy. We are here to talk about Richard Pazdur being named director of CDER.
I guess we should just jump right in, and the question is, this is significant, we all know it’s significant—I’d love to hear what your thoughts are on this. Do you want to start, Ellen?
Ellen Sigal: Sure. Well, it is very significant. Initially, I think he turned down the job—that’s public knowledge. And then, all of a sudden this week there were calls coming to all of us. And I said, “Oh no, that’s never going to happen. No, he’s not doing it. And I was very assured…”
And then, after a while, I kept on trying to get Rick and then I couldn’t get him. Then I said, “Oh my God, this may be true. This may be true.”
This significance is not because I was surprised. The significance is significant for all diseases.
The culture, the stability of FDA and what can happen in every rare disease or in diseases that we’re fighting right now that aren’t rare, has leadership has been extraordinary.
And his innovation for cancer and now to take that to other diseases is really an exciting opportunity.
Paul Goldberg: Karen?
Karen Knudsen: I couldn’t agree more. I agree with everything you said, Ellen, and I think it’s at some level I am thrilled to death that he did it. But I’m also at some level not totally surprised, because when I look back at what he’s done, it seems to me that he’s always had this strong service-minded component and a really good track record of being patient centered when it comes to decision-making.
I think he’s gotten a reputation for championing patient input and the regulatory process. He’s worked very closely with advocacy groups that we’ve both been affiliated with across a wide spectrum in oncology of everything from metastatic disease to rare cancers, and really trying to put together policies and regulation that are going to adhere to strategies to let the science go faster, and at the same time protect those that would benefit from new technologies and new therapeutics.
So, I’ve admired that.
And then his focus really on meaningful endpoints, on quality of life, on survivorship—that resonates with patient advocacy groups.
And, bottom line: his ability to make us nimble as a community, but without losing scientific rigor, I think really makes him very perfect for this. And it’s clear he is in this to do better by people and increase health.
Paul Goldberg: Do you think that the administration knew what it got? I mean, because you get stability with him, do you think they really understand the significance of this? Because if he doesn’t get what he wants, he’s just going to walk.
Ellen Sigal: It’s hard to know whether they know what they got. They were in a situation where they needed desperately to have stability.
They knew they had to have someone within the agency. If they know what they bought, I don’t know.
But what I’m telling you is what they’re going to get is real science, real rigor, real ability to make innovation happen, and to work in a way that will be important for patients.
So, they may not fully understand. Obviously, everyone knows, everyone knew he was capable and certainly what he did in cancer was legendary, but I think they may be surprised at what may come out of what he’s doing, because he did not take this job unless he can make change.
Because his initial position, a week ago, was, “No, I’m not going to do it.”
So, obviously, he has the ability to hire and perhaps have the resources he needs to implement his vision.
Karen Knudsen: Yeah—hallelujah!
And I think none of us in leadership want to take a job if we don’t think that we can make a difference, so, clearly, he’s got a green light in front of him. I’m delighted by it.
Did the administration know what they got? I don’t know. I’m with Ellen on that, but they’ll sure find out.
I mean, I think that this administration that’s focused on or really is publicly declaring that they want to improve health knows that the FDA has to be a major lever toward that.
And if you think back to reinforce what Ellen said, if you think about the innovation for the Oncology Center of Excellence, thinking about very new models of how to bring things to approval, which is essential for modern therapeutics that don’t necessarily fit neatly into a single regulatory bucket, I think moving that beyond oncology into other disease areas or other areas of health is going to bring fresh new rigor into the FDA and improve the lives of all of us.
I hope they’ll see what they got pretty quickly.
Ellen Sigal: Yes, I think Karen’s right, I think she’s exactly right. They may not know, but they will know quickly what this really means, and I think they will be very pleased.
Paul Goldberg: Yes, it’s interesting, because the most interesting thing he has said—and we’ve all spoken with him for many years, often—he said in a meeting, actually in a conversation with you, Ellen—”Nobody goes to a doctor to get a drug or biologic or a device. They go to a doctor to get treatment for a disease,” which is what he’s really saying is that FDA must reorganize itself based on what, based on diseases, disease groups.
That’s obvious.
He’s been talking about this for 25 years.
Karen Knudsen: And prevention. And prevention though too, and he absolutely gets that.
And we’re seeing so much innovation along that side that I think you need a bold thinker, an innovative thinker who’s going to be able to determine what are the regulatory pathways and trial strategies that are going to let us exponentially improve prevention for diseases like cancer.
Ellen Sigal: I agree. I mean, he comes in with a full plate. He’s also very focused on what probably needs to happen. He definitely will want more integration. He’s not going to want silos of all the divisions.
We know now that these silos don’t work, and that is something he’ll have an opportunity to integrate other disease experts in different areas, whether it’s epidemiology, prevention, or immunotherapy.
He’ll be able to really take that across the board.
Karen Knudsen: When I think about the enablers of how he’s going to be successful, maybe this goes without saying, but I think he knows how to navigate the territory, right?
The most skilled of us who’ve never served in government would probably have a challenge of getting into this position at FDA and being effective without understanding how to really navigate the system that is government.
Paul Goldberg: Maybe we should do a little bit of history, because he comes to FDA in 1999. By 2001, Ellen Stovall sets up, essentially, a movement to get him named FDA Commissioner.
There was a total move to do that. It was kind of fun. And then also director of oncology and so forth.
But in between there is the ImClone scandal, which also causes a move to bring all of these places together and the biologics and drugs. And this has been going on and on and on, and it’s still going on, because people at CBER don’t necessarily want to go into the Oncology Center of Excellence.
And what happens now is it seems that the systems have all crumbled, essentially.
The FDA is weak and maybe he can build it now…
Ellen Sigal: Yes, I think he would not have taken this job unless he felt he could execute and make changes that were meaningful. He knows that there isn’t a huge amount of time, but the fact that he knows the organization and the government so well and has been in it for so many years is a major advantage.
Nobody, no matter how nimble or how bright or how they have a vision to even find out where the bathrooms are is a challenge.
I think that I know that he knows government and he will have government behind him, I am sure.
It’s a rare quality where you have patients, where you have scientists, wherer you have industry, and the media that really adore you and think you’ve done a really good job.
There have been some critics in the past, but, honestly, he has a very, very, very broad constituency that will help him implement what he needs to do.
Karen Knudsen: I think that’s such an important point—and under multiple and very different administrations.
That’s really, I think, bodes well for the future. And if you’re thinking about who to put in this position, why not pick someone from oncology?
I mean, look at what we’ve done as a field.
Investment in science has resulted in a 34% reduction in cancer mortality since 1991. And that only happens when patients get access to new diagnostic prevention and therapeutic strategies.
So, oncology has really been able to convert science into improved outcomes and health.
But then, when you dig into the history of what he’s done, that incorporation of real-world data certainly focused on evidence, but also developing adaptive trial designs to match the new science, I think it was a great choice to pick someone who’s clearly done that in oncology and now positioned them to be successful across all disciplines.
Ellen Sigal: One thing we haven’t talked about, but we have to talk about, in addition to the science leadership, and ability to attract wonderful people is his empathy.
He knows personal loss. He knows what it means. He’s very empathetic to patients and the real-world patient that is struggling every single day.
Every decision is never going to be exact, and he has to be able to take risks, and he understands those that are important to patients. We can’t ever forget in the back of his mind, not only what he went through, but he understands this instinctively that he’s protecting and helping patients.
Paul Goldberg: I was actually thinking, preparing for this, who might be the person in the history of oncology who would have a similar fundamental influence—really shaping the field.
And that would be Gordon Zubrod. Those two guys have really are the most important people in the field.
Gordon Zubrod set up the cooperative groups. He started viral oncology program [at NCI], which now means immunotherapy. [He brought about the cures of] childhood leukemia, and so forth.
But Rick shows up in 1999 and sets up the entire structure of approval of cancer drugs which shape everything. And without him, we wouldn’t be where we are.
Ellen Sigal: We have to give credit to the fact that he knew that there had to be organizational structures. Remember CBER; taking monoclonal antibodies from CBER and putting it into CDER?
He understood that was going to be incredibly important. He also worked closely with his colleagues. He had good relationships. So, he worked with Janet Woodcock, he worked with every director of the FDA has admired and had to deal with Rick, because they knew that he was serious about what he was going to do.
There was nobody that I know in the leadership of FDA in the years that I know that didn’t admire Rick and his talents.
Karen Knudsen: Agreed.
Paul Goldberg: I don’t think he would’ve taken his job if he weren’t promised… I don’t know what those premises are worth, but if he weren’t promised that he would be shielded from political influence, there’s no way—he wouldn’t.
Ellen Sigal: I’m positive that he would be shielded and would not accept political interference.
And I’m sure that was discussed. I don’t know exactly what made him change his mind, but I am sure that he will be free to really implement the science that is right for the FDA.
It’s never 100%; right. And there’s going to have to be some risks, but I’m sure that he will do the right thing.
Karen Knudsen: Of that, I am certain.
Who can really guarantee someone that you’re going to be shielded from political influence?
Yes, you want to create a clear pathway for a new leader to be able to execute on what they’re being asked to do, and this is so critical for all of us in the US and beyond.
But what I have full confidence in is that he will always be guided by doing the right thing for patients.
Ellen Sigal: That’s exactly right.
Paul Goldberg: A little bit of history. Again, when he came in, drugs were being approved based on two randomized [trials] for full approval. And overall survival, of course.
And for accelerated approval, there were these monstrously large phase II trials for tumor shrinkage.
So, we’re talking about paleo-oncology.
By the time these new drugs started showing up, he was there…
Ellen Sigal: He was there, but he understood, and was able to work with it, and take the risks inherent in it, and not stop the evolution of this science that was so important.
Karen Knudsen: Yes, I think what the point Ellen is making is so absolutely critical.
So, he knew that there had to be significant rigor to protect the population. But at the same time, rigor didn’t mean that you couldn’t be nimble, didn’t mean you had to slow down.
You just had to have a different way of thinking. That different way of thinking is going to continue to adapt. The kinds of ways that drugs will be assessed, brought to market, and the way that they’ll be delivered are so fundamentally different than they have been in the past.
I mean, the way that chemotherapy will be delivered is in a much smarter way or more specific way.
Maybe I’ll withdraw the word smarter, but more specific way than it has been before with antibody-drug conjugates.
The way radiation therapy will be delivered is very different with radio ligands.
The way that trials will occur and the regulatory pathways are going to be quite different, that’s just from those perspectives.
But then also, we are fulfilling the promise of precision medicine. The way those agents are going to be developed and brought into the regulatory pathway are just different.
And so, I think having somebody who’s shown that ability to adapt and still protect at the helm is what’s key.
Ellen Sigal: Yes, those are hard things when you think about it. Adapt, which means taking some risk, and on the other hand, not to do it really hurts people.
So, I think he knows those lines and we’ll navigate them well.
Paul Goldberg: If he leaves, the whole thing crumbles, you know.
Ellen Sigal: Well, let’s hope that doesn’t happen, let’s hope.
I think Rick is quite serious about this job. I think he probably made it extremely clear that what he needed to be successful, and I think the administration will want that.
There is no way they’re not going to accept… Even though it’s been quite challenging, I think they want to get to the right place to help patients, and we can only hope for that.
Paul Goldberg: There’s one thing I cannot understand, and he’s CDER. CBER is run by Vinay Prasad, his counterpart.
Vinay Prasad before he came to FDA, essentially made a career of knocking down, or trying to knock down, the things that Paznur built.
I mean, you cannot imagine two people more opposite. So, how do you think that can work out? And where’s [FDA Commissioner Marty] Makary in all of this?
Ellen Sigal: You’re asking hard questions.
Look, what I know is that people have been very respectful of Rick. That up until now, the interactions have been okay.
If that’s the case with him taking the CDER job, we can only hope that will continue. But clearly, it’s a risk, because Rick is going to have to make very difficult, very challenging changes and he’s going to need the support of his colleagues.
And we can just only hope that Makary will understand what he needs to do to make Rick successful.
Karen Knudsen: And Rick has a history of being very transparent. And I would imagine those conversations amongst all the individuals that you just talked about happened before he agreed to take the job, I would deeply suspect.
Paul Goldberg: I was just thinking going back to before he came to FDA, FDA was generally unreachable, and if you were able to get through, which required some work, they were also incomprehensible.
Ellen Sigal:
Correct.
Paul Goldberg: You could really figure out, the first thing Rick did was show up, start talking to ASCO and the ACR. Bring in the advocates like you and Ellen Stovall, who was his huge friend, and just open the doors.
And that’s an actual transparency.
Ellen Sigal: Yes, he did more than open the door, he listened. He understood the advocacy community and obviously the scientific community that Karen comes from, so he did both.
Karen Knudsen: He really did. Showing up and being present, and to your point, listening, Ellen, I think made a ton of difference.
And then one of the things that he didn’t directly do, but under him happened with his instruction that I was really thankful for is in prostate cancer field, my field, all of a sudden we went from having no new therapeutics for decades to having the science now lead to new potential life-extending therapies that became FDA-approved.
The second line androgen receptor therapeutics, PARP inhibitors, other things. I was chairing ASCO GU, which is the biggest subspecialty ASCO, and we asked Rick’s team to bring someone in to tell us the story.
I think it was enzalutamide, of what was that regulatory pathway of the things you can share with us. Let’s do a Q&A, tell us the arc of how you were first contacted about this and what questions you had and what guidance you gave and how that led to an appropriate dialogue between those that were behind the drug itself and then the FDA.
And it was so instructive for all of us, and I can’t help but to think made everybody better, those that are trying to bring drugs to clinical trial and design those trials appropriately to ask the right questions and do the right thing by patients, but also what is the FDA really looking for and what, give us insight into that black box, that window of what the conversation is actually like.
Now, that one had a happy ending that the drug got approved and men are living today because of it.
But I think that transparency that was brought about by Rick, I think it was Paul Kluetz who came in and did it for us at ASCO GU, and we loved it so much.
And then that became a mainstay of ASCO GU, like, “Please come, please continue telling us the stories and the dialogue so that we can understand how to go faster and make sure that we’re giving every patient an opportunity to survive cancer with new potential therapeutic life-saving therapies.”
Ellen Sigal: The other thing is, we’re all not afraid to criticize him, so there are two sides of it.
There is the part, Rick, you’re doing great, or Rick, we’re not happy.
Not fast enough… or whatever it is because you’re never quite happy, ever, with the FDA. It’s too fast or too slow. And that amount of criticism is pretty huge.
When the community thought he wasn’t right or when he wasn’t going fast enough, he was willing to understand. He may not agree, but you felt free to discuss issues with him and have a dialogue without him taking it personally, and I think that’s very important for a leader.
Paul Goldberg: He’s been slammed pretty hard a number of times.
Ellen Sigal: Correct.
Paul Goldberg: He also built one of the best oncology departments in the world with almost no money. He was hiring people from NCI fellowship program, thanks to Mary—and some of these folks are gone now.
And I know it’s really must be very difficult to leave or to bifurcate as he’s going to have to be chief of oncology and CDER.
Do you think he’s got the people, he’s got the slots to hire?
Ellen Sigal: If you were to talk about all the attributes of Rick Pazdur, and there are many, one of the things that is really critical is he’s always recruited excellent people.
He takes it quite seriously.
Not only does he recruit them, he keeps them. Now people will move on for all different reasons, but the ability to get the right people to want to work with or for Rick is a special sauce that has been really critical for his success.
Karen Knudsen: Mark of a great leader.
Wanting to have critical feedback and being open to that critical feedback and being mission-oriented, I think is all part of what makes a great leader. And people want to follow individuals like that.
And a great leader as well, wants the people underneath them to challenge them and continue to make, because isn’t every organization, CDER included, on a consistent journey of self-betterment, of iteration, of how we think differently, move with the science?
Ellen Sigal: And there are a lot of critical people. It’s like having a 13-year-old, a teenage daughter. What can I say? Nobody’s ever quite happy at any time.
Karen Knudsen: Yeah.
Paul Goldberg: Yeah. I mean none of us, the three of us are prone to gushing, but we are gushing.
Ellen Sigal: Correct, correct.
Karen Knudsen: Yes, we are.
Paul Goldberg: If he has time, he’ll probably watch this and say, “Have they gone crazy? What are they talking about?”
I think we should probably talk about Mary a little bit more.
Ellen Sigal: Yes, I think you are bringing up the right thing. She was his rock. She was his conscience, she was able to work with him, understand him, guide him, and for sure tell him when he was wrong.
That ability to have someone you trust that isn’t just admiring you, that is your partner and your best friend and the trust that he had, and Mary would always speak her mind.
I admired that woman so much. She was just a gift from heaven. I don’t know how, tears come to my eyes when I think of her right now. She was extraordinary, and I think she helped him, and we need to give her the credit for what Rick became.
Paul Goldberg: I think he took a job and it became a mission, and he’s still on the mission. And 25 years later, 26 years later now almost, we’re seeing what happened, which is he is now able to implement the vision that he brought more or less brought to FDA, I think.
Karen, what do you think?
Karen Knudsen: Hey, I totally agree. And as speaking to somebody whose whole organization is dedicated to collapsing that timeline between a discovery and the time that a life-saving therapeutic hits a patient, I’m all about it. I’m thrilled to death of the choice and I’m just not sure we could have done better.
Ellen Sigal: Karen, you were right on.
You’ve said it better than any of us, or certainly I could have said it. That is exactly right. We’re all behind him and we’re thrilled, and I think he will benefit all diseases, and I think we’ll all be extremely happy.
Paul Goldberg: I agree. Thank you so much.
Karen Knudsen: Now we know, the three of us can gush. We’ve proven ourselves capable.
Ellen Sigal: And we’re not gushers. Any one of us are not gushers. That’s what’s so funny about this. All of us can be quite critical.
Paul Goldberg: That’s right. That’s true. Well, thank you so much.
Karen Knudsen: All right.
Ellen Sigal: Thank you.
Jacquelyn Cobb: 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: Until next time, stay informed, stay engaged, and thank you for listening.
