In our ongoing series called “OncoDaily Dialogues”, we consistently feature prominent individuals in the field of oncology. We showcase their achievements, obstacles they’ve overcome, and significant moments in their journey.

Today, we’re honored to welcome Mikkael Sekeres, M.D., Chief of Hematology at Sylvester Comprehensive Cancer Center, which is part of the University of Miami Miller School of Medicine.

In this episode of OncoDaily Dialogues, Dr. Sekeres and Roupen will discuss drug development, clinical trials, the FDA approval process, and Dr. Sekeres will provide insights into how the FDA operates. Additionally, they will explore the most mind-blowing advancements currently shaping the drug development field.

About Mikkael Sekeres

Dr. Mikkael Sekeres holds the position of Professor of Medicine and serves as Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, the University of Miami Miller School of Medicine. He is the chair of the medical advisory board for the Aplastic Anemia and Myelodysplastic Syndrome (MDS) International Foundation. Previously, he chaired significant bodies such as the Oncologic Drugs Advisory Committee of the FDA, the MDS Research Fund of the Dresner Foundation, and the Cleveland Clinic Enterprise Pharmacy and Therapeutics Committee, where he also held the role of Vice-chair for Clinical Research within the cancer center.
Dr. Sekeres is an active member of American Society of Hematology, where he serves on the Executive Committee and chairs the Committee on Communications, as well as the American Society of Clinical Oncology and the Southwest Oncology Group—Leukemia Committee.
He is author and co-author of over 450 manuscripts and 650 abstracts, which have been featured in reputable journals. He has also writen 60 essays for The New York Times and has authored 8 books.
Dr. Sekeres focuses on the study and treatment of myeloid malignancies, with a particular interests on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in older adults.
During an interview, Dr. Sekeres said he loves New York-style thin crust pizza, wishes he could tie a cherry stem with his tongue, and enjoys Nirvana’s album “From the Muddy Banks of the Wishkah”. He’s also good at plumbing, electrical work, and carpentry.

About Roupen Odabashian

Dr. Roupen Odabashian is an accomplished Internal Medicine Physician and Hematology/Oncology Fellow with a profound commitment to advancing healthcare through clinical practice, research, and technology. Currently based at the prestigious Karmanos Cancer Institute, Dr. Odabashian is actively involved in pioneering cancer treatments and conducting clinical research.

In addition to his clinical work, Dr. Odabashian is a multifaceted healthcare professional. He hosts podcast at OncoDaily, engaging with leading experts in oncology to share valuable insights with the medical community. Dr. Odabashian also contributes his expertise as an advisor at Spiraldot Health and Mesh AI, supporting innovative ventures in healthcare technology and collaborative scheduling to combat clinician burnout. With his diverse roles and unwavering dedication, Dr. Odabashian exemplifies a commitment to driving positive change in healthcare.

Oncodaily Dialogues: Mikkael Sekeres/ Hosted by Roupen Odabashian

0:14 – Process of drug approval in FDA
4:10 – Urgency of drug approvals
7:41 – Dr.Sekeres’s role in FDA
11:16 – Advice for young generation
13:58 – Working in FDA is not only about vetting the drugs
14:41 – Most exciting thing right know in drug development field
16:57 – Advice for pharmacological companies and drug for drug developers

About OncoDaily 

OncoDaily was founded in 2023. It is a US-based oncology media platform, which features the latest news, insights, and patient stories from the world of oncology. Within a short period of time it became one of the leading oncology media platforms globally.

OncoDaily gathers content from various sources, including social media posts from renowned oncologists from all over the world, news from oncology societies and cancer centers, patient and survivor stories, and career-related information for professionals.

The mission of OncoDaily is to empower patients, survivors, and professionals with the knowledge and inspiration they need to fight cancer. The motto of OncoDaily is “Cancer doesn’t take a day off – neither do we”.

Previous episodes of Oncodaily Dialogues

OncoDaily Dialogues #1 – Harout Semerjian / Hosted by Roupen Odabashian

OncoDaily Dialogues #2 – Piotr Wysocki / Hosted by Roupen Odabashian

OncoDaily Dialogues #3 – Andrés Wiernik / Hosted by Roupen Odabashian

OncoDaily Dialogues #4 – Therese Mulvey / Hosted by Roupen Odabashian

OncoDaily Dialogues #5 – Sarkis Meterissian / Hosted by Roupen Odabashian

OncoDaily Dialogues #6 – Navneet Singh / Hosted by Roupen Odabashian

OncoDaily Dialogues #7 – Aparna Parikh / Hosted by Roupen Odabashian

Follow the transcript below

Roupen Odabashian: Doctor Sekeres, I’m so happy to have you here today.

Mikkael Sekeres: It’s so nice to be here. Thanks so much for the opportunity.

Roupen Odabashian: Thank you so much. Given your experience and the expertise with the FDA and drug approvals, can you just walk us through the typical process of drug gaining FDA approval from the initial development to the final approval?

Mikkael Sekeres: Sure. Well, as you probably know, this can be a lengthy process. So it may start with a proof of concept study, some kind of postulated mechanism of how a drug works, whether it targets a protein that’s made by a gene mutation, or a protein expressed on the outside of a cell, and that is then demonstrated, of course, in test tubes. Once that seems to show some efficacy, it’s then transitioned to animal models, and animal models of specific diseases that we treat.

Once it shows efficacy, there are actually formulas for translating the dose of the drug in a small mammal, like a mouse, to the dose of a drug in a human. And it then enters first in human studies. As it’s walking through the steps, an investigational new drug application (IND), is filed with the FDA, and that allows a drug to be explored in humans for the first time. And that’s the very first trial that occurs.

So depending on the results of that trial, a company can then engage the FDA actually really early in what the best pathway is to get a drug approved. And that’s something that’s referred to as breakthrough therapy. So if you hear that a drug is given breakthrough therapy designation, that means there’s something kind of exciting that’s happening in very early phase studies. The FDA agrees with the sponsor that it’s exciting, and the FDA will actually work closely with multiple meetings with the sponsor, in how to design a potential registration path.

Depending on the population prevalence of a certain disease, drugs then can even go to single arm studies, potentially if they demonstrate enough efficacy and safety, a drug can then get what’s referred to as accelerated approval, meaning that the FDA sees the data. The FDA is willing to recognize an interim marker of a clinically meaningful benefit and approve a drug based on that, with the caveat that a confirmatory trial then has to be conducted to confirm, at the very least, the initial activity that was seen with the drug and safety. But ideally to demonstrate that a drug actually improves somebody’s overall survival.

So when I refer to an interim marker of a clinically meaningful benefit, you can imagine what that might mean. So for example, overall response rates, duration of response, even sometimes progression free survival will be defined as an interim marker of a clinically meaningful benefit, the clinically meaningful benefit being overall survival or improvement of patient reported outcomes. What we will casually say the FDA defines as lives longer or lives better. To sum up. We start with preclinical models, move it into clinical models, then develop a registration plan to get this available to people who desperately need it. For single arm studies or rare diseases, this might be an accelerated approval path for more common diseases and randomized trials this will be full approval.

Roupen Odabashian: So from what I’m hearing, it looks like even there is a process sometimes to outweigh the benefit versus the risk, If I have a drug that’s making a huge, significant difference in people’s lives. So the FDA can recognize the urgency of that and like, accelerate the approval process.

Mikkael Sekeres: Yeah, it’s great, I like how you use the word urgency. What the FDA will fall back to is what they call the totality of data. So they don’t look at one data point in isolation. For example, you can have a drug that significantly prolongs overall survival, right? That should be a no brainer. That drug should be approved for people. Well, not if it has a treatment related mortality rate of 75%. Right. So that’s the balance of efficacy and risk. And then put into that equation a couple of other factors. One is the severity of disease. And the other aspect is the public health need for a drug.

So severity of disease, I specialize in treating people who have leukemia or myelodysplastic syndromes or myeloid neoplasms. Right? Somebody who’s older who has acute myeloid leukemia, the chance that that person will be alive and disease free five years after diagnosis is less than 10%. So their disease itself, you could argue, has a mortality rate that approaches 90%. Now, obviously, there are other factors in older adults. Somebody has heart disease. They may die of a heart attack. It’s hard to figure out if that heart attack would have occurred anyway, or it was exacerbated in the setting of their leukemia, but there’s a 90% chance that person will be dead five years after their diagnosis. So life threatening disease.

So if we come through with a drug that has a 10% mortality associated with it, you might say, you know what? If it prolongs someone’s survival, if it doubles their survival, maybe that’s okay, maybe that’s sort of worth it in the totality of data. On the other hand, if we’re treating somebody who has high blood pressure and the mortality related to the drug in the next year was 10%, you would say, that’s nuts. There’s no way we would approve that. So think about that in terms of totality of data.

The other part of that is public health need. I think we saw a lot of this play out recently with Aduhelm, which was approved for the treatment of Alzheimer’s disease. It really didn’t work that well. And in fact, there is a neurology advisory committee that met that said that, that basically said to the FDA, this drug really doesn’t work that well. We don’t think we would approve it. But there’s such a huge public health need for a treatment for Alzheimer’s that I think the FDA said, you know what? We’re going to take a risk on this drug. So put into that. Use your word urgency. Right? That urgency was there to bring a drug that, you know, wasn’t necessarily life saving, but may have helped a few people with Alzheimer’s because there really isn’t anything else out there. And if you’re thinking about this from a drug development perspective, gee, the bar for approval is going to be a lot lower for diseases where there ain’t anything out there as opposed to the 10th drug to treat the same disease and disease stage.

Roupen Odabashian: Yeah, that makes sense for sure. And now I want to talk more about your role in the FDA. So can you describe your role in the FDA advisory panel, in the drug approval process and how you contribute to the final decision?

Mikkael Sekeres: Yeah. So I was on the Oncologic Drugs Advisory Committee, or ODAC, for five years, and I chaired it for two years. I’ve subsequently and actually, before I go on, let me say that’s a once in a lifetime appointment. So you would think that’s the sort of thing where, gee, if you’re good at it and you really like it, and you think this is important, you’re on it for years and years and years.

And actually, that’s not the case. You get one appointment as a standing member of ODAC your entire career, and that appointment lasts somewhere between, you know, usually 3 to 4 years. And I got an extra couple of years out of it because I was chair. Since then, I’ve been called back as an ad hoc member of ODAC, and FDA will do that. They’ll call in folks who are disease specialists to help out with the committee, because the committee is comprised of people with a variety of different specialties. So I obviously focus on hematologic malignancies. There are folks on the committee who may have expertise in lung cancer and breast cancer in melanoma. There’s a patient representative who’s on the committee and there’s an advocacy representative who’s on the committee. So it’s this interesting balance of of people.

And ODAC is often called by the FDA. Let’s put it this way, not when it’s a slam dunk decision. If this is a no brainer, a drug that prolongs overall survival has minimal toxicities. Everyone loves this drug. FDA isn’t going to call an ODAC. They know what the decision is going to be. So ODAC is often called when it’s not as clear cut. And I can give you an example. There are some drugs where they may improve duration of response. Right? And significantly improve it compared to the control arm Or they may improve progression free survival. But when the overall survival data comes in, that experimental drug is a little bit worse than the control arm.

So what does the FDA do in that situation? Do they approve the drug because wow, it had this gangbusters great duration of response improvement compared to the control arm, when people not only aren’t living longer but may be living shorter with the drug. Or FDA may call ODAC together when they want an advisory committee to help them with some aspect of clinical trials moving forward. For example, there’s going to be an ODAC that’s called, in April of this year to focus on minimum measurable residual disease and how that can be used for drug approval. Right? Which of course is a really fascinating topic.

Measurable residual disease is a great example of an interim marker that’s reasonably likely to predict a clinically meaningful benefit. You can’t look at a patient and say, hey, you’re MRD negative. Isn’t that great? You don’t you feel better? They won’t feel any difference if their MRD negative or if they have a little bit of MRD positivity. So it’s not clinically meaningful at that time. The meaning comes at what that implies for disease recurrence and overall survival.

Roupen Odabashian: It’s a very interesting role. And that brings me to my next question. We have tons of young oncologists and professionals in their young career, and if someone is listening to this and they say, wow, this is very exciting. And I’m saying that right now. So what advice would you give someone who’s young in the beginning of their oncology career to be where you’re at right now and have similar roles with the FDA?

Mikkael Sekeres: Yeah. So there are a couple of paths to doing this, and one is working at the FDA and one is being an advisor to the FDA. You know, my first experience with the FDA was, boy, a long time ago, 15 years ago, there was a drug that was a farnesyltransferase inhibitor that was developed to treat acute myeloid leukemia, and it was called, tipifarnib, or Zarnastra. And I was one of the clinical experts, the sponsor asked to come and testify in front of the FDA to argue about how this was a great drug.

Now, this drug resulted in remission rates in older adults that weren’t that great, probably about I think it was about 15% at the time. So we went before ODAC and tried to make the case that this was a drug that was worthy of approval. And man, ODAC just slammed us. I mean, it was just brutal taking us out to the woodshed on this. And I left this meeting thinking to myself, you know what? I want to be on the other side of that table. I don’t want to necessarily be the one who’s here arguing about a drug that works. Okay, but really may not change the lives substantively of most people. So, you can actually be nominated to be on ODAC. And I was nominated because I play a role in a patient advocacy group. I chair the medical advisory board for the Aplastic Anemia and MDS International Foundation, and patient advocacy groups can recommend members of onto ODAC.

The other route is current members of ODAC or former members of ODAC can recommend people to be on ODAC. So, that was the way that I made it on to ODAC. I have worked with fellows who chose instead to actually join FDA, and coming right out of fellowship to join FDA. And I think that’s a very rewarding job, to be part of a team that is vetting drugs and determining whether they should be made available to cancer patients who desperately need new drugs.

Roupen Odabashian: Won’t the FDA require you to have the clinical experience, at least for years, to know what is clinically significant and what is not, or like to have at least tons of publication under your belt.

Mikkael Sekeres: It’s a great question. Not necessarily but what FDA does support is your continuing to see patients in clinic. So there are members of FDA who not only work at FDA on teams that are vetting drugs, but they also have a clinic at an area hospital and continue to see patients. So they can kind of see practically how the fruits of their labor are playing out.

Roupen Odabashian: That’s very exciting. I should check their website right now after this call. What excites you the most about, like the I know there are tons of changes, in hematology we just have a Journal club now, like soon, and there are tons of research, but, like, what excites you the most about drug development in the field right now?

Mikkael Sekeres: There are a few things. So, I don’t think we’ve even started to recognize the importance of technologies like Crispr. Right? We’re starting to see people who have germline mutations, heritable diseases in hematology like sickle cell, who are being cured of their disease. That just blows my mind. That is remarkable. So I think we’re going to see Crispr play out more and more, particularly with heritable hematologic disorders for acquired hematologic disorders. Again and again, we’ve now seen mutations specific therapies that have been developed. And I think this is the start of that. We recognise, and of course, the complexity of different cancers.

So a single drug targeting a mutation isn’t going to be transformative in most of these cancers, with the exception of diagnoses like chronic myeloid leukemia, where it’s what I refer to as a one hit wonder. You have one mutation, causes one protein change. You can have one drug that can really change the landscape of treatment for that. Most hematologic malignancies are the acquisition of multiple hits, multiple mutations. So I think more and more we’re going to be seeing these drugs targeting mutations combined with either other drugs targeting mutations or classic cytotoxic therapy, obviously within lymphoid malignancies, we’re continuing to see the power of immunotherapy depending on how you define that. And the impact that that’s had on patients who have multiple relapsed lymphoid malignancies, we haven’t quite seen the power of immunotherapy in myeloid malignancies outside of monoclonal antibodies. but the more of these drugs that we put together, the more that we’re able to move the bar with every single intervention the longer people are going to live.

Roupen Odabashian: And, my last question is like, so you’ve been on this role for a while, and what advice would you give, pharma companies or researchers who are developing new drugs and trying to bring something new to the market? How they should navigate the FDA approval process?

Mikkael Sekeres: Yeah. You know, you can get lost in the excitement of drug development, and caught in your own bubble to convince yourself that a drug is really awesome, when it may not be. And I think people lose sight of the fact that the FDA can be accused of being opaque and very difficult to understand, but I guess I don’t see it that way.

The FDA or people like we are, and they’re people who recognize what’s valuable to a patient and what isn’t valuable to a patient. And if you keep the primacy of benefiting a patient in front of you with drug development, you’re going down the right path. And let me explain a little bit. Let me be more concrete what I’m talking about. In earlier phase trials, particularly phase two trials, we’ve seen over and over again responses that are exaggerated. For example, recently there was a development of an Anti-cd47 monoclonal antibody, Magrolimab, for the treatment of myeloid malignancies. And the initial study that came out reported a 92% overall response rate. My God, this thing. It was crazy. We never see those sort of response rates in myeloid malignancies. When you really drill down to it though, a lot of those responses were patients who had morphologic leukemia free states or marrow CRS. In other words, blasts that went to less than 5% irrespective of blood counts.

Now, I’ve always thought that’s a nonsense response criterion, and we actually showed in the MDS Clinical Research Consortium that marrow CR is no better than stable disease, in terms of how long people live. Right? So it’s really a non response. But the sponsor for that drug really convinced themselves that this was something special, despite the fact that when you took those marrow series and morphologic free states out of the analyses, the responses were good, but they weren’t all inspiring. Well, they used that initial study to move on to randomized trials. And lo and behold, those trials were utter failures. So I think you know, focusing on something like an overall response rate. Yeah, the overall response feels great.

But unless somebody is living longer or living better, it really ultimately becomes meaningless. And you have to remember that an overall response rate is hypothesis driving. It’s not an end in itself. So let’s turn back to what I said earlier. If drug developers, investigators and sponsors are focusing on the primacy of really improving a patient’s life and what that means to that person from the very start, they’re always going to be advancing a drug that is meaningful to patients and has a better chance of being approved by the FDA.

Roupen Odabashian: Sweet, That answers my question. Thank you so much Doctor Sekeres. I really appreciate your time. And today that brings us to the last part of the episode. Thank you so much for being here with us today.