Chimerix Advances ONC201 toward Regulatory Approval
By Alex Keown
March 4, 2023
Bolstered by positive Phase II data, Chimerix, Inc. remains on track for full enrollment in its Phase III ACTION study evaluating ONC201 in patients with H3 K27M-mutant glioma, putting the company one step closer to potential approval.
In a year-end earnings call March 2, Chimerix Chief Executive Officer Mark Sherman said data readouts from the study are expected to begin in 2025, with a final readout in 2026. Chimerix is enrolling sites in the United States and Israel. The trial design of the ACTION study allows for early stoppage if interim survival analysis are strong enough, Sherman said. If results are consistent with the independent analysis previously reported at the Society for Neuro-Oncology meeting last year, Sherman said the Durham-based company anticipates being able to stop the trial prematurely and begin discussions for accelerated approval.
“Recent independent analyses reported overall survival advantage in patients treated with ONC201, which has further reinforced our confidence in the ACTION trial and the commercial opportunity for ONC201. With a successful PFS analysis, we plan to speak to the FDA about seeking an accelerated approval and then would incorporate the overall survival analysis as a post marketing requirement,” Sherman said.
ONC201 is the first member of Chimerix’s imipridone class of anti-cancer small molecules which selectively targets Dopamine Receptor D2 (DRD2) and ClpP.
Data shared at the SNO conference in November 2022 showed ONC201 provides a “potentially meaningful overall survival advantage” for glioma patients in the recurrent setting. The independent data announced in December supporting an ONC201 survival benefit in the H3 K27M-mutant population more than doubling median survival compared with those not treated with ONC201 26 months, compared to 12 months in the frontline setting. Overall, two external analyses presented at SNO concluded that glioma patients who received ONC201 experienced a meaningful survival benefit, the company announced.
Sherman said the independent data supports the company’s Phase II results. It also reinforces the company’s confidence in the probability of success of the Phase III ACTION study.
“We exited 2022 with a clear focus on our oncology pipeline and the initiation of the Phase 3 ACTION trial of ONC201 in patients with H3 K27M-mutant glioma. Patients with this deadly disease are in desperate need of therapeutic options and ONC201’s robust foundation of data underscores its potential as a highly differentiated asset,” he said. “It’s our plan that we would move ahead with that submission based on the data we would see if it’s positive.”
Beyond ONC201, Chimerix is also developing ONC206, a second generation imipridone that has demonstrated anti-cancer activity in pre-clinical models of various central nervous system (CNS) tumors and other malignancies. ONC206 is a ClpP agonist and DRD2 antagonist that has enhanced in vitro potency relative to ONC201. ONC206 is currently being evaluated in Phase I dose escalation clinical trials for adults with recurrent primary central nervous system tumors.
Preclinical and early clinical observations in initial low dose cohorts suggest that ONC206 may be effective for CNS tumors beyond those that harbor the H3 K27M mutation addressed by ONC201, Chimerix reported. Sherman said the company learned of a confirmed response to treatment with ONC206 in one of the early dose cohorts.
“We wouldn’t ordinarily highlight a single case of tumor response, but because this happens so early in the escalation and in a patient with non-H3 K27M glioblastoma. This is a setting where we’ve never seen a tumor response with ONC201. It stands out as an important signal for ONC206 an important signal about potential broader market opportunities,” Sherman said.
Chimerix remains in a strong financial position following the $238 million sale of small pox drug Tembexa to Maryland-based Emergent BioSolutions in the fall of 2022. The sale of Tembexa provides the company with significant financial runway into 2027, Sherman said.
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Alex Keown is a freelance journalist who writes about a variety of subjects including the pharma, biotech, and life science industries. Prior to freelancing, Alex has served as a staff writer and editor for several publications.
