ESSA Pharma announced the discontinuation of its Phase II study on masofaniten, which it was evaluating for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
The decision came after a futility analysis of data from the study indicated there was a low probability of achieving the prespecified primary endpoint.
ESSA was evaluating the drug in a head-to-head study against Pfizer and Astellas’ blockbuster prostate cancer drug Xtandi (enzalutamide).
This decision, jointly reached by senior management and the board of directors, followed a protocol-defined interim review of safety, pharmacokinetics and efficacy data, said ESSA in a press release.
The review revealed that enzalutamide monotherapy, the standard of care for this patient group, achieved a significantly higher response rate than anticipated based on historical data.
The company explained there was “no clear efficacy benefit” for the masofaniten-Xtandi combo when compared to Xtandi alone.
The combination of masofaniten and enzalutamide was well-tolerated, showing no new safety signals and maintaining a safety profile consistent with that observed in Phase I studies.
Enzalutamide is also an androgen receptor (AR) inhibitor that first received US Food and Drug Administration (FDA) approval in 2012 for CRPC. Xtandi sales topped $5.3 billion in 2023, placing it amongst the world’s top ten best-selling drugs.
Masofaniten (previously known as EPI-7386) is a first-in-class investigational oral small molecule that targets the N-terminal domain of the AR.
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“Providing a meaningful clinical benefit to patients in our clinical trials, along with a robust safety profile, is of utmost importance to us at ESSA,” said David Parkinson, MD, president and CEO.
“We designed this randomized study to rigorously evaluate the clinical benefit of adding masofaniten to enzalutamide. We made the difficult decision to terminate this Phase II study following the interim analysis because we concluded that the emerging efficacy profile of masofaniten combined with enzalutamide would not likely meet the primary endpoint of the study, nor our internal requirements for a prostate cancer therapy candidate,” explained Dr. Parkinson.
The Phase II study was designed as an open-label, two-arm 2:1 randomized trial with a target enrollment of 120 patients from clinical sites in the US, Canada, Australia and France. Of these patients, 80 were in the combination arm and 40 in the enzalutamide monotherapy arm.
The interim efficacy analysis included 52 enrolled patients (48 percent of the planned total) who had at least one post-baseline prostate-specific antigen (PSA) measurement, and 41 patients (34 percent of the planned total) who had completed at least three months of follow-up.
The study’s primary endpoint was the proportion of patients achieving a 90 percent or greater reduction in prostate-specific antigen (PSA90), a key biomarker for prostate cancer. Secondary PSA-based endpoints included PSA50 (reduction of 50 percent or more in PSA levels) response, PSA50 and PSA90 response rates at 12 weeks, and time-to-event measures (which were not mature at the time of interim analysis).
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The FDA granted Fast Track designation to masofaniten for treating adult male patients with mCRPC who are unresponsive to standard therapies. ESSA holds exclusive global rights to masofaniten.
ESSA has two other assets in its portfolio, both inhibitors targeting the AR N-terminal domain like masofaniten. However, they are not clinical trial ready at the moment.
Richard Glickman, chairman of the board said in the press release that the company is now “actively focused on conserving capital and will begin a strategic process to explore and evaluate a variety of options aimed at maximizing shareholder value.”
The disappointing trial results come after ESSA’s announcement this summer that it was anticipating several significant milestones in the coming nine to 12 months.
In addition to masofaniten, another prostate cancer AR inhibitor also bit the dust this year. Oncternal Therapeutics discontinued its dual-action AR inhibitor after it underperformed in a Phase I prostate cancer study.
As of September 30, 2024, ESSA reported cash reserves and short-term investments totaling $126.8 million, with net working capital of $124.3 million (unaudited). The company said it holds no long-term debt.
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