FDA Approvals

Alireza Mansouri: Big Milestone in Oncology – FDA Approval of Dordaviprone

Alireza Mansouri/LinkedIn

Aug 17, 2025, 16:34

Alireza Mansouri: Big Milestone in Oncology – FDA Approval of Dordaviprone

Alireza Mansouri, Associate Professor at Penn State Health, shared a post on LinkedIn:

“Big milestone in oncology:

The FDA has approved dordaviprone (ONC-201) as the first systemic therapy for recurrent H3 K27M-mutant diffuse midline glioma in patients 2 years and older.

This targeted oral drug brings hope for those battling this devastating brain cancer. As someone passionate about medical advancements, I’m thrilled to share what this means and the incredible journey behind it.

The path to FDA approval for any new drug is long and fraught with challenges – ONC-201’s story is no exception. The original chemical compound was discovered in the 1970s, but it took some time for it to have oncology applications. In the early 2010s, through lab screening for compounds that could activate natural cancer-killing pathways, it faced early obstacles like a structural error that led to ineffective copies being tested.

Overcoming this required rigorous science, from preclinical models to human trials. Founded by academics, the company Oncoceutics navigated funding hurdles, partnerships (like with MD Anderson), and an acquisition by Chimerix in 2021 to scale up. Clinical trials involved proving safety in diverse patients, gathering data on effectiveness, and meeting strict regulatory standards. It’s a reminder that drug development often takes 10+ years, billions in investment, and resilience against setbacks – only a fraction of candidates succeed.

This approval targets a particularly challenging disease: H3 K27M-mutant diffuse midline gliomas, including deadly forms like diffuse intrinsic pontine glioma (DIPG) in children. These tumors grow in critical brain areas, making surgery risky or impossible, and they resist traditional chemo and radiation. With a historical survival rate of just 9-11 months, families face immense emotional and logistical burdens, especially since it’s rare and under-researched.

Clinically, ONC-201 has shown remarkable impact. By selectively stressing cancer cells to trigger self-destruction (via pathways like TRAIL), it has extended median survival to about 21 months in studies, with some patients experiencing tumor shrinkage and improved quality of life. Data from five key trials and expanded access programs highlight durable responses, minimal side effects (like mild fatigue), and its ability to penetrate the brain – a huge win for non-invasive treatment.

On the horizon, the ongoing Phase 3 ACTION study is evaluating ONC-201 for newly diagnosed patients, potentially in combination with other therapies to boost outcomes further. Research is expanding to other brain cancers and related compounds like ONC-206, paving the way for personalized medicine in neuro-oncology.

Kudos to the scientists, clinicians, advocates, and brave patients who’ve driven this forward. What are your thoughts on accelerating drug approvals for rare cancers? Let’s connect and discuss!”

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