The Cure Starts Now

Case Report in the Journal of Neurosurgery Highlights Potential of ONC201 in H3 K27M-mutant DIPG


Oncoceutics announced today the publication of an article entitled "First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M–mutant pediatric diffuse intrinsic pontine glioma: a case report” in the Journal of Neurosurgery (authored by Matthew D. Hall, M.D., MBA). The article summarizes the medical history of a 10-year-old girl with a diffuse intrinsic pontine glioma (DIPG) brain tumor. Following radiation therapy and treatment with ONC201 on a compassionate use basis, she developed near complete resolution of her presenting neurological symptoms for almost one year, enabling her return to school and participation in many normal activities.

DIPG is a serious and rare disease with a dismal prognosis and no viable treatment options. It predominantly affects children and young adults, and it is the most common form of brainstem glioma in this age group., a resource network for the disease, summarizes the disease characteristics as follows: "Currently, outcomes for most patients are poor, with a median survival of less than 1 year from diagnosis. Radiation therapy can shrink tumors, temporarily improving some symptoms and delaying the progression of the disease, but in almost all cases, the tumor continues to grow. So far, clinical trials have not shown that currently available chemotherapy drugs, radiosensitizing drugs (drugs that make tumor cells more likely to be killed by radiation therapy), or biologics (medical products created by biological processes, such as vaccines or gene therapy) benefit patients. Because of their location in the brainstem, DIPGs cannot be removed surgically. New approaches to treating DIPG are urgently needed."

ONC201 is an investigational drug developed by Oncoceutics that is being studied in several clinical trials for use against DIPG and other brain tumors. The underlying mechanism of the drug involves the interception of a specific receptor for dopamine, called DRD2. DRD2 is a neurotransmitter that is misused by malignant glioma cells to boost their growth. Tumors that harbor a certain mutation of a highly conserved histone protein, i.e. H3 K27M, are particularly sensitive to ONC201 in spite of the otherwise aggressive growth that this mutation confers. DIPG is one of the tumor types that exhibit a high prevalence of this mutation.

The patient described in the article has shown prolonged clinical benefits and is approaching almost two years from diagnosis, although ONC201 was administered only when symptoms progressed after radiation was completed. This supports further investigation of ONC201 in H3 K27M-mutant gliomas, including DIPG. As a result, Oncoceutics has significantly expanded its pediatric clinical program for ONC201. The company's ongoing pediatric trial for ONC201 in H3 K27M-mutant high-grade gliomas including DIPG (NCT03416530) was extended with additional treatment arms, a pediatric oral solution formulation was introduced, and ONC201 treatment was extended to newly diagnosed DIPG patients with concomitant radiation.

The company further implemented an intermediate size Expanded Access Protocol (EAP) to provide access to ONC201 for patients that might benefit from the drug but are not eligible for participation in the ongoing clinical trials. The EAP was made possible by the support of the Food and Drug Administration and their high priority effort to facilitate access to promising medicines for patients with serious or immediately life-threatening diseases or conditions when no comparable or satisfactory alternative therapy options are available (see recent FDA statement). The program is also supported by The Musella Foundation, The Cure Starts Now Foundation, The Michael Mosier Defeat DIPG Foundation, Cancer Commons and xCures.

“We are delighted to see a novel concept to treat this horrible disease emerge and show traction in clinical settings. We have followed the development of ONC201 for some time and are excited about the emerging data in both, children as well as young adults that are expected to become public later in this year." - Keith Desserich, Chairman of the Board and Co-Founder of The Cure Starts Now