The FDA’s accelerated approval of Modeyso for diffuse midline glioma with an H3 K27M mutation units the stage for extra therapy developments.
The U.S. Meals and Drug Administration (FDA) granted accelerated approval to Modeyso (dordaviprone) for sufferers with diffuse midline glioma with an H3 K27M mutation, a transfer which one knowledgeable defined may set the stage for much more therapy developments sooner or later.
“Now that this drug is on the market, doubtlessly, you might consider mixture therapies and different novel methods to attempt to construct on this step,” Dr. Patrick Wen advised CURE in an interview. “The drug may be very nicely tolerated; most focused therapies are usually not that straightforward for sufferers to take, this one is definitely very straightforward. You’re taking it as soon as every week, and there might be some fatigue, nausea, complications, however more often than not, sufferers do not feel unhealthy on it in any respect, and a number of them will not have unwanted effects that they will let you know about. So hopefully it will permit the drug to be pretty simply mixed with different medicine, and that may construct on these preliminary steps
Wen, is the Director of the Middle for Neuro-Oncology at Dana-Farber Most cancers Institute and Professor of Neurology at Harvard Medical College in Boston, and was the senior creator of a research revealed within the Journal of Scientific Oncology that discovered monotherapy with Modeyso to be well-tolerated, with sturdy and clinically significant effectiveness amongst sufferers with recurrent H3 K27M-mutant diffuse midline glioma.
Wen spoke with CURE in regards to the significance of the approval and what comes subsequent.
CURE: What needs to be the massive takeaway from the FDA approval of Modeyso?
Wen: Of all of the forms of gliomas, that is most likely the toughest one to deal with. Because it’s within the midline, it isn’t resectable by surgical procedure, and sufferers often do not reply to straightforward chemotherapies. All these sufferers have is radiation, which works for quite a lot of months, after which the tumor recurs. Consequently, most sufferers have a life expectancy of a few 12 months or so. It is a horrible illness that happens in younger adults and infrequently in kids. Till this approval, there was no therapy for these sufferers apart from radiation.
This approval is predicated on a research that is not for all diffuse midline glioma sufferers with an H3 K27M mutation. It was finished primarily for sufferers who had thalamic gliomas, and primarily in adults. It is because it is extremely arduous to inform if a drug is working in these tumors. For example, the extra widespread diffuse intrinsic pontine gliomas (DIPG) are usually not enhancing, so it’s totally arduous to measure the tumor. The FDA wished a set of sufferers in whom they may assess the response price. That is why this research checked out 50 sufferers with a measurable tumor; they weren’t DIPG sufferers or spinal wire sufferers. The approval was based mostly on the response price and the sturdiness of the response.
So, it is undoubtedly an essential step ahead in a subject the place nothing has been accredited, but it surely solely advantages a subset of sufferers. We nonetheless want a number of work to enhance the outcomes. Nevertheless, now that this drug is on the market, we may doubtlessly consider mixture therapies and different novel methods to construct on this step. The drug may be very nicely tolerated—most focused therapies are usually not that straightforward for sufferers to take, however this one is definitely very straightforward. You’re taking it as soon as every week, and there might be some fatigue, nausea, or complications, however more often than not, sufferers do not feel unhealthy on it in any respect, and a number of them will not have unwanted effects they may let you know about. Hopefully, it will permit the drug to be pretty simply mixed with different medicine, which is able to construct on these preliminary steps.
How does Modeyso work to combat most cancers?
It is thought to work in two methods. One is that it blocks some receptors that dopamine receptors two, two and three. By blocking it, it slows down tumor progress. It additionally stimulates a unique receptor that impacts the metabolism of the tumor cells, and by doing so, causes the tumor cells to barter adjustments that make it extra prone to die. So, that is by stimulating one thing referred to as ClpP and mitochondria.
Each these mechanisms are regarded as in play. It is not fully clear which one is the extra essential one.
With this therapy possibility on the desk, what are unmet wants that also stay for sufferers with glioma?
It was based mostly on the research for measurable illness. It is primarily thalamic gliomas, that are increased up within the mind stem. We do not have as a lot details about the effectiveness for the diffuse intrinsic quantum glioma, that are the actually devastating tumors in kids.
The corporate might have extra data on that, however I’m not conscious of the ultimate knowledge from as a result of there are a number of ongoing trials. It is actually for the thalamic sickness that this remedy is useful. Hopefully will probably be considerably useful for the DIPGs additionally, however we do not have as a lot data.
What’s subsequent for Modeyso, by way of analysis?
This was an accelerated approval by the FDA, so it nonetheless wants closing approval, and the corporate, Jazz, has an ongoing section 3 trial this drug in newly identified sufferers with diffuse midline glioma, so hopefully that trial, when it is accomplished, will verify these preliminary outcomes and result in full approval of the drug. In order that’s nonetheless pending, that trial is occurring exterior the U.S. With the approval of this drug, I feel we will stay up for mixture therapies with different brokers that is perhaps helpful for these tumors, and so I feel that might be an essential step ahead.
It’s extremely arduous to work with two medicine that aren’t accredited, but when one in every of them is accredited, it makes it simpler to do these research.
References
- “FDA grants accelerated approval to dordaviprone for diffuse midline glioma,” by the U.S. FDA. Information launch. Aug. 6., 2025. https://www.fda.gov/medicine/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma
- “ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma,” by Dr. Isabel Arrillaga-Romany. The Journal of Scientific Oncology. Could 1, 2024.
- “FDA Approval of Modeyso ‘Essential Step Ahead’ For Sufferers with Glioma,” CURE, Aug. 15, 2025; https://www.curetoday.com/view/fda-approval-of-modeyso-important-step-forward-for-patients-with-glioma
- “FDA Approves Modeyso for Sufferers with Diffuse Midline Glioma,” CURE, Aug. 6, 2025; https://www.curetoday.com/view/fda-approves-modeyso-for-patients-with-diffuse-midline-glioma
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