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Aidan Fraser Interviews Brigitte Widemann, MD about Selumetinib, the first FDA-Approved Drug for NF

By April 16, 2020December 18th, 2023NF1, Science & Research, Story of NF

In this interview, NF1 patient Aidan Fraser discusses the development of the MEK-inhibitor drug selumetinib with his doctor, Brigitte Widemann, MD, who was the principal investigator of the selumetinib clinical trial at the National Institutes of Health. Aidan lives with NF1 and was on the selumetinib clinical trial for many years. In this interview, Aidan and Dr. Widemann are speaking to each other from their respective homes, as an in-person interview was cancelled due to the COVID-19 social distancing guidelines.

Watch the interview below, or scroll down to read their conversation in its entirety.



AIDAN: First of all, how are you doing?

BRIGITTE: I’m good, Aidan, it’s nice to see you. As you know there’s lots of things going on right now with Coronavirus and other things that kind of capture everybody, but I am well and I really look forward to talking with you today.

AIDAN: Yeah, that’s actually one of the first things I had wanted to ask. Because I can imagine things down at the NIH and areas like that are insane right now. And– So, how is that?

BRIGITTE: I think it’s a big adjustment for everybody, Aidan. And I guess in your city, even much more so.

AIDAN: Yeah.

BRIGITTE: But they are all making sure that patient safety, and the safety of the staff, comes first. We get lots of new guidelines, almost every day, about what we are doing and how we ensure safety is there. We communicate a lot more like you and I are communicating right now. You know, Facetime, WebEx, Zoom, to be make sure that we continue to do the mission critical work. But at the same time, lots of people are teleworking because we really want to emphasize patient and staff safety.

AIDAN: So, obviously the main thing we’re going to talk about today is the selumetinib clinical trial. The first thing I really want to ask is, can you tell us what led to investigating selumetinib, and drawing up a clinical trial?

BRIGITTE: I’ve known you since you’ve been three or four years old, I believe. I looked back yesterday actually, and as you know, by training I’m a cancer doctor. A cancer doctor for children. And I have been at the [National Institutes of Health, NIH] for a long time. And at the NIH, my work has focused on hopefully developing effective therapies for children with cancers. But then, I noticed that a number of the drugs that we are using and testing on children with cancers actually could have effects that are beneficial to patients with NF1. And this is how my work in NF1 started.

You’ve been, and I hope that it’s okay to say, you’ve been participating in trials since you’ve been a little boy. So we’ve known each other for at least 15 years. And so after conducting a number of clinical trials, there was some evidence that, potentially, a MEK inhibitor, which blocks an important pathway in these tumors could be beneficial. There was data from an animal model in leukemia, with NF1 and then also later, from Dr. Nancy Ratner in Cincinnati, in a mouse model of NF1 that the MEK inhibitors might work. So when we started our trial, with a MEK inhibitor, it was with a hope that this might actually work for patients. And you were a participant, I hope it’s okay to say that, in the phase one study.

AIDAN: Of course.

BRIGITTE: As you know, this was the first trial, at least that I conducted, where we for the first time we saw shrinkage of these tumors. So the bottom line in your question, is – it was after conducting a number of clinical trials that we got to selumetinib, and this was the first one that actually worked. At least to a good extent.

AIDAN: Then I can imagine that it was very hard to get something like this off the ground, as we’d never really had anything before that we could actually present it to, say, the FDA. Was there any real struggle in doing that?

BRIGITTE: I wouldn’t call it struggle, necessarily, but you’re absolutely right. This is not easy for a number of reasons. One, what was really hard, actually in the beginning, was to get the MEK inhibitor for NF1. As you know there are several other MEK inhibitors, too. And it was really difficult because the drug companies initially would say, “Okay, NF1 is not a cancer, the drug may have side effects for these patients with NF1 that do not have cancer. What is the risk to benefit ratio?” And the second thing was that we wanted to give this medicine to young patients. Because we know the tumors grow most rapidly in young patients. And so that was a challenge for us. I think it was really hard to get the drug company to buy and to give this to patients with NF1 in the first place. That was a challenge.

I think the second challenge that we had was after we had shown in the phase one study, that you participated in, “Hey, these tumors are actually shrinking,” the next step was, “How do we get this, potentially for an FDA approval?” And then it was that the FDA told us, “Look, shrinkage is nice, but you have to show that patients medically get better.” And that was damaging because as you know, the tumors can be in so many different places. And so we had to design a study that would show the clinical benefit. Those, I think, were two of the struggles or challenges we had.

AIDAN: I would like to just go back to something you said in your last point. Which was that I know a lot of people have been slightly confused about it, but you’re saying that there’s more than one MEK trial. I know a lot of people just say “MEK” but there’s more than one, now.

BRIGITTE: Yeah, so you’re absolutely right. So, let me clarify that. So selumetinib, that’s the MEK inhibitor that we are testing. We had a phase one study that was to test the best dose. And then we did a phase two study to show the clinical activity. So that’s with selumetinib. But there was also a study with a MEK inhibitor called trametinib. That is a study with binimetinib, and there is another MEK inhibitor that is also in clinical testing. So there are actually a number, now, of MEK inhibitors that have been tested in NF1 and in plexiform neurofibromas, to show that these tumors also shrink.

AIDAN: I do know that a lot of people are becoming a little confused about that. They keep hearing the term “MEK” thrown around. So, thank you for clarifying. Really, the big thing I want to ask now is, because as we’re talking about how amazing selumetinib is. Do you recall the moment when you realized that it was working?

BRIGITTE: Yes, I actually do. And you know, Aidan, when you have conducted the number of clinical trials with nothing really working, the first patient that we enrolled on the phase one study, after five months we did the MRI, and I could see, visibly, that the tumor had shrunk. I remember thinking, “Oh, my goodness, this cannot be true.” I always try to stay very realistic and grounded. So I said, “Okay, this is the first patient. Let’s see, this could be a fluke, maybe this is not right.” But the second patient, I couldn’t wait for the second patient to be rescanned, and we saw the same [tumor shrinkage]. And when I saw it, I thought “Okay, we have two patients now where we’ve seen that the tumors shrink at the first evaluation.” I would say that I knew then, that very likely, selumetinib was different than all the other things that I had tried before. And that was really an amazing feeling because it gave me, for the first time, the hope that they’re really onto something that may help patients with NF1.

AIDAN: So selumetinib is working, what do you think it will mean if it gets approved by the FDA for patients?

BRIGITTE: What it means for the patients, I think that’s a really good question. Because, as you know, selumetinib is not a cure. Selumetinib doesn’t make the tumors disappear. What it does for many patients, it stops the growth and it shrinks the tumors some. And it helps patients with symptoms such as pain, sometimes airway function, strength, range of motion. So, it makes patients feel better. But I would say for patients it’s really important to know that while this would be a huge step forward, we still have to do a lot more. And I don’t want patients to expect that this will take, like the plexiform or other symptoms away completely. The other thing it’s important, you have to take it. You know, it’s a medicine that is taken every day, and you probably, I guess you could speak to that how difficult it can be to take a medicine twice a day, every day.

AIDAN: Yeah, especially when you are a lot younger and in school, and in classes. Yeah, you can’t really build your schedule. Something I’ve learned personally is that as you get older, you can kind of build your schedule around it. You can go to your employer, and say, “I’m on this medicine,” and they’re like, “Oh, well, I will give you your rest at lunch period.” Whatever works. Like you come up with a time that works for your medicine, and just take lunch then. But like, if you go to school, there’s like 50 other kids to consider in your class.

BRIGITTE: You might actually give great advice to people, because you’ve been on the MEK inhibitor for a long time, now. Right?

AIDAN: Yeah, yeah. So, another thing I would just like to ask is – what made you decide to work with NF?

BRIGITTE: It really started, Aidan, when I realized that the drugs we were using on cancers might help patients with NF1. And my former mentor, Dr. Peter Adamson, he had actually, prior to myself, he brought in a few kids with NF1 for clinical trials that were primarily designed for kids with cancer. And meeting these young patients, I realized that while NF1 and the tumors that patients develop for the most part are not cancer tumors, they cause a lot of problems and suffering. So when I got the hunch that there might be drugs that could work for NF1, you know, we started getting into the field, and then, I have to say, I got really attached to my patients and it’s a wonderful aspect of being able to see patients year after year, like you. You know, I have patients that were little kids that are now grownups and it’s very wonderful to see that, Aidan. And so that is another thing that got me more and more hooked on NF. And of course the track of success, but there’s so much more than needs to be done.

AIDAN: So, selumetinib is a drug now used for NF1, but I was wondering, would you say there can be any benefit for people with other types of NF, or other types of tumors like schwannomatosis?

BRIGITTE: It’s great question. I do think for sure that it might help people with NF who have some other manifestations, like patients with NF1 and gliomas, some types of brain tumors. There have been studies that show quite exciting, very exciting, actually, activity. And there will be a clinical trial that compares, in patients with glioma, the selumetinib to a standard treatment which is a chemotherapy. And I look forward to seeing that study, very much. It might help patients with skin tumors, cutaneous neurofibromas. And it may help with other NF-related manifestations.

There’s a study that the Children’s Tumor Foundation sponsored, or provided funding for, to look at cognitive effects. So I think a lot can still be studied for NF. Your question regarding other types of tumors like schwannomatosis or NF2. It’s interesting that while these are very distinct diseases, we have seen that sometimes the pathways that are involved might actually be important. I cannot conclude that selumetinib would have a role. But that should be tested I think, rigorously, pre-clinically now that we know we have good models like that can be tested before it goes into patients.

AIDAN: Thank you. Is there anything you’d like to say to the community as a whole, about the way the future looks for NF?

BRIGITTE: I would like to say, thank you, Aidan. I feel every success and progress is the result of the NF community, working together. And the biggest thanks, for me, goes to the patients. Like you, and people that participate in research that have not given up when we did not succeed. I feel the NF community is very special, and maybe that’s because that is the community that I know the best. That people really work together. When you, as young people, went to the FDA and talked to the FDA to educate them about NF1. That was a highlight. And when I saw that, in particular, that you participated and I knew you. I feel the groups that are supporting the research work together, it’s not working against each other. So for me, it would be a huge “thank you.” And if the NF community continues to do what we’re currently doing, we will make additional progress, Aidan. That will hopefully result in even much better results than what we’ve accomplished to date.

AIDAN: Well, thank you so much. And thank you for taking the time out of your day to do this.

BRIGITTE: I enjoyed it, Aidan, I really knew this was the highlight for my day, today. So thank you very much, I appreciate it.

AIDAN: Thank you so much. Well, have a nice day.

BRIGITTE: You, too, Aidan. Bye-Bye.


Click here to read more about the Children’s Tumor Foundation announcement about the FDA’s appoval of the first-ever treatment for neurofibromatosis. 

Click here to access the Children’s Tumor Foundation MEK Resource Center with more information on selumetinib, interviews with patients and researchers involved in this journey, as well as information for NF patients.