Medidata, a Dassault Systèmes Company, announced the FDA has given its support for the use of a Medidata synthetic control arm (SCA) in a Phase III registrational trial in recurrent glioblastoma (rGBM). According to the company, this marks a precedent-setting acceptance of a hybrid external control (which combines synthetic control arm patients with randomized patients) in a Phase III trial in an indication that to date had used traditional randomized controls.
“The Medidata SCA is an external control built from historical clinical trials data from an archive of more than 22,000 clinical studies,” Ruthie Davi, vice president of data science at Acorn AI (a Medidata company) told Outsourcing-Pharma. “Working with historical clinical trials data is an advantage because the usual clinical trial style endpoints and covariates are directly available. Another benefit of the SCA is the extremely high rigor that goes into the collection of historical clinical trial data.”
Medicenna Therapeutics, a clinical-stage immunotherapy firm, will use the hybrid external control arm in the trial for rGBM, an aggressive form of brain cancer. The hybrid external control arm reportedly will reduce the number of patients required to be assigned to the control therapy in the trial, provide rigorous scientific data, and enable speedier development of the product.
The Phase II single-arm trial preceding this study also involved a synthetic control arm. Estimates of the treatment effects based on the synthetic control arm were part of the briefing information provided to the FDA for justification of the use in Phase III.
Davi explained the SCA stands to benefits patients and researchers in several ways.
“This benefits the patient enrolling in the trial,” she said. “It allows fewer patients to be exposed to a standard of care therapy that they are not going to potentially benefit from; this is especially true for indications like rGBM, where there are no established therapies to prolong life significantly, and where the NCCN guidelines recommend patients enroll in a clinical trial.”
“Second, it speeds up pharmaceutical research and development of new molecular entities (NME) and allows clinical research to be conducted in an indication where it otherwise may not have been completed (due to high patient drop out rate in the randomized control arm),” she added.
“Third, it does not compromise the scientific evidentiary standards. We construct our SCAs using sound statistical methodologies that are thoroughly researched and well-accepted in the statistical peer-reviewed literature,” Davi commented.
Further, Davi told us, Medidata has performed extensive work to validate the science of the SCA, including case studies with Friends of Cancer Research: one in non-small cell lung cancer and the other in multiple myeloma. Medidata reportedly showed that using the SCA had the same estimate of overall survival as a traditional randomized controlled clinical trial.
Fahar Merchant, president and CEO of Medicenna Therapeutics, said his organization is “impressed” with the team from Acorn AI for providing a “scientifically rigorous rationale” for the trial design.
“The FDA’s acceptance of this unique design will expedite completion of the Phase 3 trial in rGBM, allowing earlier access of MDNA55 for a disease with poor prognosis and high unmet need,” he said.
