On November 25, 2019 INHIBITOR Therapeutics, Inc. (OTCQB: INTI), a biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to inhibit progression of cancerous and non-cancerous proliferation disorders, reported that the company has submitted an Investigational New Drug (IND) Application to the U.S. Food and Drug Administration (FDA) to seek clearance to initiate an IND-opening clinical study as a two-part, multi-center, randomized, double-blind, placebo-controlled, Phase 2b clinical trial that will evaluate the efficacy and safety of SUBA-Itraconazole capsules dosed in combination with docetaxel and prednisone in patients with metastatic castrate resistant prostate cancer (mCRPC) (Press release, Inhibitor Therapeutics, NOV 25, 2019, View Source [SID1234551673]). The proposed trial will be named PREDICT (Prostate Response Evaluating Docetaxel Itraconazole Combination Therapy).
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Nicholas Virca, INHIBITOR’s President and CEO, said: "Following a pre-IND meeting with FDA in the first half of this year, FDA granted us a face-to-face End-of-Phase-2 (EoP2) meeting, which I am pleased to announce occurred last month. During that meeting, we gained FDA guidance and agreement on our protocol and statistical analysis plan for our proposed PREDICT trial. FDA indicated that we can follow the 505(b)(2) regulatory pathway given previous FDA approval of itraconazole. Assuming positive results demonstrating an improvement in radiographic progression-free survival (rPFS) as our primary endpoint, FDA indicated that the general design and planned analysis of our study would adequately address the objectives necessary to support a New Drug Application (NDA) submission. Further, FDA indicated that the final analysis of the key secondary endpoint of overall survival (OS) can occur following submission of the NDA for approval in the United States."
Mr. Virca continued: "I would like to acknowledge the stellar efforts of our regulatory and clinical team members over the last nine months to achieve this level of progress for our SUBA-Itraconazole Prostate program. Approximately 23,000 men in the U.S. are diagnosed each year with late-stage mCRPC that no longer responds well to androgen deprivation therapy (ADT) or previous treatment with chemotherapy or newer stand-alone anti-androgen therapies such as abiraterone, enzalutamide or apalutamide. We believe that SUBA-Itraconazole Prostate has the potential to address an unmet need in these patients, who exhibit disease progression or who have discontinued the other therapies due to toxicity or other reasons."
About Itraconazole in Prostate Cancer
In late-stage prostate cancer, up-regulation of the Hedgehog pathway in cells results in oncogene expression, which can interfere with the binding of ADT drugs to the androgen receptor (AR), causing biochemical resistance leading to mCRPC. Itraconazole acts on the essential Hedgehog signaling pathway component called smoothened (SMO) in human cells in a different manner than the FDA-approved drug vismodegib by preventing the ciliary accumulation of SMO normally caused by the Hedgehog pathway. Itraconazole also has a much shorter half-life than vismodegib, which may be the reason it appears to have fewer side effects than what has been reported for vismodegib in recent publications regarding its use in treating basal cell carcinoma. Thus, itraconazole may be more suitable than vismodegib for use in combination with chemotherapy due to its lower toxicity profile. Itraconazole has been tested as a treatment for mCRPC in a multi-institutional Phase 2 trial led by a prominent U.S. university and published in 2013.This trial showed that 90% of men with prostate specific antigen (PSA)-doubling times of less than 6 months, who achieved therapeutic levels of itraconazole, showed promising PSA reductions that correlated significantly with rPFS. The improved bioavailability of SUBA-Itraconazole may provide additional benefits to prostate cancer patients in two ways: 1) by achieving higher therapeutic levels of itraconazole at lower doses than those reported in the Phase 2 study, which used the generic formulation of the drug, and 2) by reducing the dose of chemotherapy based on enhanced uptake of docetaxel in the presence of itraconazole.