Medicenna gains precedent-setting FDA approval to design a hybrid Synthetic Control Arm^® for a Phase 3 registrational trial

About the Customer

Medicenna, a mid-sized clinical-stage immunotherapy company, is on a mission to combat the world’s toughest diseases. One of Medicenna’s most promising molecules is MDNA55, which uses a highly specific interleukin-4 receptor (IL4R) targeted therapy to treat recurrent glioblastoma (rGBM).

Key Takeaways

In Phase 2, the Synthetic Control Arm (SCA) enabled Medicenna to better understand the expected survival benefit and supported their proposed hybrid Phase 3 design.
In a precedent-setting regulatory decision, the FDA agreed to consider the use of a hybrid SCA in Medicenna’s Phase 3 registrational trial.
The hybrid SCA will reduce the number of prospective control patients by approximately 2/3rds.
This design offers a greater chance to receive the experimental drug, easing recruitment, reducing drop-out, and accelerating timelines without compromising scientific interpretability.

The Challenge

Glioblastoma is one of the most aggressive forms of cancer with very limited treatment options. Patients typically survive less than 15 months after first diagnosis and only 6-9 months following relapse.

The nature of rGBM makes it extremely difficult to recruit and retain patients for study in a clinical setting. MDNA55 offers a promising opportunity to improve outcomes for this aggressive cancer. But Medicenna faced difficulties interpreting the results of their single arm Phase 2 study. The company needed to design a Phase 3 registrational trial that could successfully recruit and retain patients to demonstrate the effects of MDNA55 for registration.

The Solution

Medicenna selected Medidata AI to create an SCA to re-analyze their Phase 2 trial and better understand the treatment effect. An SCA uses patient data from past clinical trials instead of a new control group. It provides a scientifically rigorous comparison in scenarios where a control group is hard to recruit or retain.

Medidata AI used the results of the Phase 2 SCA analysis to design a hybrid SCA and statistical analysis plan for Medicenna’s confirmatory Phase 3 trial to demonstrate the efficacy of MDNA55. This design reduced the number of prospective control patients needed by approximately 100 patients.

“Medidata AI literally rolled up their sleeves, helped us analyze the data, and suggested ways to improve our clinical trial design. They were essentially part of our statistical group… We worked with Medidata and leveraged that information when we went to the FDA.”

Dr. Fahar Merchant, President and CEO, Medicenna

Results

The FDA agreed to consider the use of an SCA in Medicenna’s Phase 3 rGBM trial. This was a precedent-setting regulatory decision to consider a hybrid external control (combining SCA patients with randomized patients) in a Phase 3 trial in an indication that previously used traditional 1:1 randomized controls.

In Phase 2, the SCA enabled Medicenna to better understand the expected survival benefit for MDNA55. This knowledge supported sample size calculations for the hybrid Phase 3 design.

The hybrid SCA will give enrolled patients a greater chance to receive the experimental drug, improving enrollment, reducing drop-out, and accelerating timelines without compromising scientific interpretability.

“This first true apples-to-apples comparison of the data shows that a single treatment with MDNA55 has the ability to more than double the survival rates in patients with the most aggressive form of rGBM. We hope that these results are a watershed moment in the battle against this aggressive and fatal disease, and are particularly meaningful considering that even a modest 25% improvement in survival has not been demonstrated by any of the approved treatments of rGBM in more than two decades.”