3PC-036 New therapeutic approach for diffuse midline glioma: 3-year evaluation of access to onc201 in France and Europe

<h3>Background and Importance</h3> H3K27M-altered diffuse midline gliomas have a poor prognosis in adults and children (less than 1 year after the diagnosis), with current treatment strategies relying on radiation therapy that merely slows disease progression. Recently, ONC201 (dordaviprone), a drug developed by Chimerix, demonstrated promising results in a clinical trial conducted in the US only. To address the lack of availability in France, the French Medicines Agency (ANSM), following recommendations from paediatric oncology and neuro-oncology experts, initiated a compassionate use programme led by Gustave Roussy. This programme allows French and European patients access to ONC201 through a compounding mechanism and the S2 reimbursement process. <h3>Aim and Objectives</h3> The primary aim was to ensure and centralise ONC201 safe access to patients in France and abroad. This paper reports a 3-year compassionate use programme, addressing medical and pharmaceutical aspects. <h3>Material and Methods</h3> A national access was established, where the medical indication for ONC201 was determined through national multidisciplinary meetings. Only patients with validated indications could access the treatment, and real-world data were collected to support the SACHA study. Due to the absence of pharmaceutical grade ONC201, raw materials were requalified, and identification and purity tests were carried out in collaboration with the ANSM quality control laboratory. The pharmacy department developed hard capsules and an oral solution (for patients unable to swallow) in accordance to French hospital compounding regulations. Stability of these formulations was evaluated using methods following ICH guidelines. <h3>Results</h3> More than 100 batches of capsules and 20 batches of oral solution were produced with a stability of 12 months. Over 3 years, 234 patients from 52 centres and 13 countries were treated, with a median of five treatment cycles. 10% of patients received more than 10 cycles, and seven patients (3%) exhibited a prolonged response beyond 18 months, achieving partial or complete remission. No severe adverse effects were reported. <h3>Conclusion and Relevance</h3> This study highlights the clinical potential of ONC201, with encouraging outcomes compared to gold standard radiation therapy. This collaboration between patients associations, ANSM, clinicians and pharmacists highlights the importance of hospital pharmacy for formulation development and manufacturing of safe medicines to bridge the gap of unmet clinical needs for rare disease in cancer treatment. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest