Baxter Oncology GmbH

Sesen Bio reached agreement with the FDA a week ago on the product label for its new bladder cancer drug, one of the final steps for bringing a new drug to the market. Wrapping up product labeling is usually a sure sign regulatory approval is forthcoming. But on Monday, Sesen CEO Tom Cannell said the biotech may need to run a new clinical trial. From Cannell’s telling, until receiving the FDA letter rejecting the drug Vicineum on Friday, there were no indications that the submission was in trouble. During a July 13 meeting, the agency did not flag any deficiencies in the clinical trial data, nor did it ask for a confirmatory clinical trial or require input from an advisory committee comprised of independent experts. The rejection of the drug, which the company had projected could become a blockbuster seller globally, was a “surprising turn of events,” Cannell said during a Monday conference call. According to Sesen, the FDA’s letter provided recommendations about additional clinical and statistical data analyses. Providing this information may require another clinical trial. The company added that the regulator raised chemistry, manufacturing, and controls issues. Sesen develops targeted protein fusion therapies. These drugs are made by genetically fusing a targeting antibody with another protein that’s toxic to tumors, yielding a single molecule that is rapidly taken up by the targeted cancer cell. These therapies are intended to be an alternative to antibody drug conjugates (ADC), in which a cytotoxic payload is chemically linked to a targeting antibody. While ADCs have secured regulatory approvals, Sesen has said its fusion proteins could offer efficacy and safety advantages. Vicineum, Sesen’s lead drug candidate, was developed to treat non-muscle invasive bladder cancer that has not responded to earlier treatment with Bacillus Calmette-Guerin (BCG), an immunotherapy commonly used to treat early-stage bladder cancer. The company tested Vicineum, which is injected directly into the tumor, in an open-label study enrolling 133 patients. The main goal of the Phase 3 clinical trial was to measure the complete response rate to the therapy. As of the May 2019 cutoff date, 82 patients in the study could be evaluated. At the three-month mark, the complete response rate was 39%; at six months, 26%; at nine months, 20%; and after one year, 17%. Though FDA agreed to the complete response endpoint, Cannell said that the agency’s guidance ahead of the clinical trial left the door open for another study. “In the February 2018 guidance, the FDA states that a single arm trial clinical trial with a complete response rate and duration of response as the primary endpoint, can provide primary evidence of effectiveness to support a marketing application,” Cannell told financial analysts. “However, in that guidance the FDA also makes it clear that an additional trial may be necessary.” Cannell said Sesen needs to clarify what the FDA needs to see from this clinical trial, such as whether the main goal should be measuring complete response and duration of response to the therapy. The company needs to know whether 90 to 100 patients is enough, or whether the agency wants a larger sample size. Also unclear is whether the FDA wants a study running longer than 12 months. Sesen is seeking clarity about the FDA’s manufacturing concerns. Cannell said that Vicineum made for clinical trials came from the company’s Winnipeg facility, which does not have the capacity for commercial-scale production. Sesen has agreements with Fujifilm Diosynth Biotechnologies, Baxter Oncology, and Qilu Pharmaceutical for manufacturing of Vicineum. Cannell said that Sesen must be able to show that the drug made by the company’s commercial partners is almost identical to the drug that was tested in clinical trials. Sesen was previously known as Eleven Biotherapeutics, a biotech that focused on developing protein drugs to treat eye diseases. The company shifted its focus to cancer with the 2016 acquisition of Canada-based Viventia Bio. That deal happened after Eleven reported its drug isunakinra failed a pair of Phase 3 studies, first in dry eye disease and then later in conjunctivitis. Eleven changed its name to Sesen in 2018. The FDA’s Vicineum rejection could amount to at least a two-year delay for the drug. If Sesen needs another 12-month trial, enrolling patients and conducting the study means a new biologics license application could be ready in 2023, Cannell said. After resubmission, the FDA timetable for a response is six months. As of the end of the second quarter of this year, Sesen reported a cash position of $151.1 million. Cannell said that the company believes the capital is sufficient to support the resubmission of the Vicineum application. Image by Getty Images