Diffuse intrinsic pontine glioma (DIPG) is an extremely rare pediatric brain tumor with a dismal prognosis. On average, less than 50% of patients are expected to be alive a year after diagnosis. GlobalData notes that the attrition rate of drugs for gliomas, which include DIPG, is high compared to other cancers, and there is only a 6% chance of a glioma drug transitioning from Phase II clinical trials to an approved therapy. The leading data and analytics company notes that this environment has led to there being no FDA or MHRA* approved drugs for DIPG. However, innovative approaches to generate pipeline candidates, including the use of artificial intelligence (AI), may give new therapies a chance of approval.

Sakis Paliouras, PhD, Senior Oncology Analyst at GlobalData, comments: “DIPG is a true orphan indication for which accelerated development programs and special designations are greatly needed. It could be a big opportunity, too. Rare disease drugs routinely command a $250,000-$350,000 per-year price tag in the US, which, in the case of DIPG, could easily result in global peak sales in the $70m-$95m range.”

After numerous failures of trials for chemotherapies and repurposed small molecule inhibitors in DIPG, the field has moved on to studying drugs with more innovative mechanisms of action (MOA).

Paliouras continues: “This is a high-risk, high-reward approach, and is likely to result in meaningful clinical benefit for pediatric patients within the next ten years. The most advanced approaches in the clinic with a novel MOA are ZIOPHARM Oncology’s AdRTSIL-12, Kazia Therapeutics’ paxalisib, and Bexion Pharmaceuticals’ BXQ-350.

“Interestingly, all of these compounds have secured a ‘Rare Pediatric Disease’ designation by the FDA, allowing them to progress to a potential marketing authorization faster.“

Approaches that have emerged from academic work, but still need to be clinically proven in a large-scale clinical setting, include the use of panobinostat – originating from Stanford – and the combination of vandetanib with everolimus – in development at the ICR and Royal Marsden, utilizing an initial study plan from the AI-driven drug discovery company, BenevolentAI.

Paliouras adds: “The challenge is finding a treatment that is truly innovative and offers dramatic clinical benefit, which, due to reduced understanding of the biology of rare tumors, becomes significantly more difficult.”

*Medicines and Healthcare Products Regulatory Agency