FDA Sends Warning Letter to Former Sesen Bio Trial Investigator

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Ahead of a CMC Type A Meeting between Sesen Bio and the U.S. Food and Drug Administration (FDA) scheduled for Friday, October 29, the agency published a Warning Letter to a former study investigator of the company’s Phase III VISTA trial. The warning letter was related to a 2021 FDA inspection connected to Sesen’s Biologics License Application (BLA) for Vicineum for the treatment of BCG-unresponsive non-muscle invasive bladder cancer.

Sesen Bio stopped using both the clinical site and the study investigator more than four years ago after discovering reports of professional misconduct by the study investigator. The FDA Warning Letter also notes that the study investigator failed to comply with applicable statutory requirements and regulations in conducting clinical studies. The study investigator’s medical license was also temporarily suspended on May 29, 2017, for inaccurate recordkeeping, although that did not have anything to do with Sesen Bio and the patients in the VISTA trial.

On August 13, 2021, the FDA issued a Complete Response Letter (CRL) to Sesen over the BLA for Vicineum. The agency indicated it couldn’t approve the BLA in its present form. It also gave recommendations for specific clinical and statistical data and analyses as well as Chemistry, Manufacturing and Controls (CMC) issues related to a pre-approval inspection and product quality.

At the time, Thomas Cannell, president and chief executive officer of Sesen, said, “We are deeply disappointed by this unexpected result, and it is an unfortunate day for patients suffering from BCG-unresponsive NMIBC. We remain dedicated to our mission to save and improve the lives of patients by bringing new treatment options to patients, and we intend to work closely with the FDA to understand next steps.”

In likely response, on October 12, the company announced it was expanding its CMC and clinical development teams. It hired Eun Jang as Senior Director, Analytical Sciences, and Cherie Kaefring as Director, Clinical Operations. The company noted that the hirings came as the company was preparing for CMC and clinical Type A meetings with the FDA for Vicineum.

Vicineum is a locally administered fusion protein. It is made up of a recombinant fusion protein targeting epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells. This delivers a protein payload, Pseudomonas Exotoxin A. It is designed to decrease the risk of toxicity to healthy tissues.

In addition to the Type A meeting, the company has pulled its marketing authorization application (MAA) to the European Medicines Agency (EMA) for the drug. Sesen Bio indicates this was so it could have FDA approval first before trying to enter the European market.

In its 8-K filing with the U.S. Securities and Exchange Commission (SEC), Sesen stated, “As previously disclosed, Sesen Bio intends to use information from its CMC Type A Meeting, which has been scheduled for October 29, 2021, and the Clinical Type A Meeting anticipated to occur later in the fourth quarter to determine the appropriate path forward with regulators.”

When the clinical site tied to the investigator Warning Letter was closed, five patients had completed treatment and were in a follow-up phase. No evidence has been identified that suggests the study investigator’s behavior harmed patients. Sesen Bio included the corresponding patient data from that site in its BLA to the FDA, and that data was analyzed entirely and discussed during the review.

Much about this is still puzzling and it’s not clear if the warned study investigator has anything to do with the BLA’s rejection. An August 2021 investigation by STAT found that the investigator misconduct was only part of the issues, that there were thousands of study rule violations, more than 215 of them major, and that the company failed to reveal signs of toxicity for the drug. Reportedly a patient died in 2016 from liver failure, which the company did not disclose two years later at a medical conference. In addition, there were apparently two other trial investigators reported to the FDA for serious misconduct.

However, the company has received no Warning Letters or Discipline Review Letters during the agency’s review of the BLA for Vicineum. 

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