How Mirdametinib Improves QOL for People With NF1-Associated Plexiform Neurofibromas

The FDA recently approved mirdametinib (Gomekli; SpringWorks Therapeutics) to treat adults and children aged 2 and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not seeking complete surgical resection.¹

This approval was based on findings from the ReNeu trial (NCT03962543), and in an interview with study author Christopher L. Moertel, MD, he explains how mirdametinib adds to the NF1-associated plexiform neurofibromas treatment landscape, especially for children, and the quality of life (QOL) improvements seen with it.² Moertel serves as medical director of the Pediatric Neuro-Oncology and Neurofibromatosis Programs and professor of pediatric hematology and oncology at the University of Minnesota.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

How does the recent approval of mirdametinib change the treatment landscape for NF1-associated plexiform neurofibromas, particularly for children?

Number one, it's the first approved MEK [mitogen-activated protein kinase] inhibitor for this indication that's available in a dispersible tablet. Young children who have difficulty with pills get over that, because a dispersible tablet that goes into a liquid that tastes kind of [like] a grape flavor is more palatable and obviously easier to swallow. That's number one for children.

Number 2, it's the first MEK inhibitor that's approved for adults with plexiform neurofibroma, and that's really important considering that so many patients out there in adulthood haven't had an on-label therapy to date. Those 2 things together are important.

It came to light pretty early that we were able to give this drug irrespective of meal time, so not having to take it on an empty stomach was a great advantage to this medicine also. All of those things together are great. Then obviously, the fruit of our study was that we found that many patients had very good responses to this medicine, and that quite a few patients had what we called, alluding to the waterfall plot, "deep responses. That is, responses greater than 50% reduction in tumor size. All of those things were really gratifying to see.

Can you talk about some of the main findings from the ReNeu trial that led to this approval? Were there any that surprised you or that you want to look at more in future research?

Our primary objective, of course, was confirmed response, and that worked out very well for us. A lot of patients had a confirmed response, which is defined by a greater than 20% reduction in tumor size. But a large number of patients had what were called stable disease. People with previously growing or problematic neurofibromas, at least their neurofibromas were stable or shrunk slightly, just not to that threshold of confirmed response. We used blinded, independent central review vs having a single reviewer be the source of all that. Blinded review, I think, is something that we'll be able to use in other studies going forward.

Finally, aside from looking at tumor size, the secondary objectives were looking at quality of life and pain impacts, and I think that that's going to be super important. We can't do volumetric measurement at every medical center in the United States—actually, very few, because it takes so much radiologist time. It's really going to be up to the practitioners to use this drug clinically to improve the quality of life of their patients. We looked at things like pain indexes [and] health-related quality of life and found that we had an impact on those features also, which are super important [in] taking care of our patients.

In what ways can NF1-associated plexiform neurofibromas impact QOL, and how do you measure improvements in QOL?

One of the obvious ones is cosmesis. If one of these tumors is happening on the face, the neck, or visible parts of the body, that has an impact on quality of life and how you interact with the world. The second quality-of-life impact is where the tumor is located and how it might impact the body. If it's in the neck near the airway, that's an issue. If it's by an eye, affecting vision, or by an ear, affecting hearing. If it's by major organs, it might impact those. All of those things come together to really have a significant quality of life impact.

I brought up pain earlier. Because of their proximity to nerves, these tumors can cause a great deal of pain or discomfort in both children and adults, so helping with that pain issue has a major quality-of-life impact.

Finally, we measured certain things around movement—people's ability to walk or use a limb—and impacting that, of course, has a significant impact on quality of life for those who have a gait like one of my patients, whose gait was impacted by their tumor. As the tumor shrank, their gait improved, and they were able to do everything that all the other kids were doing. So that really helped a lot, too.

References

1. Grossi G. FDA approves mirdametinib for neurofibromatosis type 1 with plexiform neurofibromas. AJMC^®. February 12, 2025. Accessed March 17, 2025. https://www.ajmc.com/view/fda-approves-mirdametinib-for-neurofibromatosis-type-1-with-plexiform-neurofibromas
2. Moertel CL, Hirbe AC, Shuhaiber HH, et al. ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN). JCO 42, 3016-3016(2024). doi:10.1200/JCO.2024.42.16_suppl.3016