On October 17, 2017 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) (“Diffusion” or “the Company”), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported that it has received final protocol guidance from the U.S. Food and Drug Administration (FDA) for a Phase 3 clinical trial with the Company’s lead compound trans sodium crocetinate (TSC) in patients newly diagnosed with inoperable glioblastoma multiforme (GBM), a type of brain cancer (Press release, Diffusion Pharmaceuticals, OCT 17, 2017, View Source [SID1234520978]). The Company has responded to all outstanding points raised by the FDA and plans to begin the trial under the protocol agreed to by the FDA by the end of 2017. The trial will compare survival at two years of patients receiving TSC concurrent with chemotherapy and radiation (standard of care, or SOC), with patients receiving SOC alone.
“Following a series of interactions with the FDA, we are gratified to have an agreed-upon protocol and to be preparing to start our TSC Phase 3 trial in patients newly diagnosed with inoperable GBM,” said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. “As previously announced, we have engaged the contract research organization to oversee this trial and have completed the Phase 3 TSC drug production run to FDA standards. On our way to opening an anticipated total of 100 sites across the U.S. and Europe, we have 17 initial sites selected in the U.S., all under one Institutional Review Board, and first patients are expected to be enrolled this year.”
Mr. Kalergis continued, “This Phase 3 study will focus on treating newly diagnosed GBM patients who have been judged by their medical team to be inoperable because of the size or location of the tumor. In Diffusion’s Phase 2 proof-of-concept trial, the inoperable GBM patients who were treated with TSC plus standard of care showed a nearly four-fold increase in survival at two years compared with standard of care patients only. Due to their poor prognoses, inoperable patients are often excluded from GBM clinical trials and have usually been treated with radiation and chemotherapy only. We are excited to bring a new treatment possibility to patients with inoperable GBM, and look forward to beginning the trial.”
About the Glioblastoma Multiforme Phase 3 Trial
The Phase 3 trial is a randomized, controlled registration trial with TSC and SOC chemotherapy and radiation, compared with SOC alone in newly diagnosed inoperable GBM patients. The primary endpoint is overall survival, either after a predetermined number of patient deaths or following successful results of an optional interim analysis. Secondary endpoints include progression-free survival (PFS) and objective response rate (ORR; tumor response) using RANO criteria, as well as patient performance scoring (Karnofsky Performance Scale; KPS), Quality of Life (EQ-5D-5L questionnaire) and corticosteroid and anticonvulsant usage.
A total of 236 patients will be randomized 1:1 at 100 clinical sites (54 U.S., 46 EU). TSC will be dosed three times each week for six weeks concurrent with standard radiation and chemotherapy as initial treatment. This will be followed by one month of rest and then adjuvant chemotherapy consisting of six monthly cycles of TSC and temozolomide given for the first week of each cycle. As such, 18 doses of TSC will be administered during initial treatment and another 18 doses will be administered during adjuvant treatment to those so randomized.
About Treatment-Resistant Cancers and TSC
Oxygen deprivation at the cellular level (hypoxia) is the result of rapid tumor growth, causing the tumor to outgrow its blood supply. Cancerous tumor cells thrive with hypoxia and the resultant changes in the tumor microenvironment cause the tumor to become resistant to radiation therapy and chemotherapy. Using a novel, proprietary mechanism of action, Diffusion’s lead drug TSC counteracts tumor hypoxia – and therefore treatment-resistance – by safely re-oxygenating tumor tissue, thus enhancing tumor kill and potentially prolonging patient life expectancy. Oxygen levels of normal tissue remain unaffected upon administration of TSC, thereby avoiding the introduction of harmful side effects.