Although the development program for fexapotide (NX-1207) was encumbered by previous failure and threatened to go into extra innings – Nymox Pharmaceutical Corp. completed seven U.S. phase III trials, by its count – the company appeared to round third base and head for home after reporting success in the long-term repeated injection group from the phase III program for its lead candidate, designed to treat benign prostatic hyperplasia (BPH) and localized prostate cancer.
Details were scant, but the company maintained that long-term outcomes in 344 patients who were given a single repeat fexapotide treatment after initial blinded treatment with fexapotide or placebo and followed for two to 6.5 years (mean 4.2 years) after initial treatment showed long-term statistically significant symptomatic improvement – measured as mean improvement of 6.5 points in the American Urological Association BPH Symptom Score – compared to phase III patients who received placebo alone (p<0.001).
Nymox said the data analysis included all treatment failures. Repeat injection was determined to be safe, with no significant drug-related toxicities or side effects reported in the study.
Based on the findings, the Hasbrouck Heights, N.J.-based firm said it plans to file for regulatory approval within the next two quarters. Nymox said it will report additional analyses and results "when available in the near future" and present the data at unspecified medical and urological meetings while seeking to publish the findings in peer-reviewed medical journals.
Company officials did not respond to inquiries from BioWorld Today.
In development for more than a decade, fexapotide has been tested in nearly 1,000 men with enlarged prostates across seven years of placebo-controlled, double-blind U.S. studies, according to the company, which financed the entire development program. Among the studies were two prospective, randomized, multicenter, double-blind trials of fexapotide as a single injection along with two U.S. repeat injection trials and three blinded long-term extension studies. Nymox also completed several phase III safety and clinical pharmacology studies – 15 in all, according to Cortellis data.
Still, two years ago, Nymox hit headwinds after top-line data from a pair of phase III studies, NEXUS-1 and NEXUS-2, missed their primary endpoints – an outcome the company blamed on a stronger placebo response than seen in previous experiments. (See BioWorld Today, Nov. 4, 2014.)
At the time, CEO Paul Averback said on a conference call, "We had never encountered any problems before and we didn't want to further complicate our studies, because they took long enough to do. Nobody has ever successfully enrolled 1,000 people for an injectable [year-long] prostate study where you had to do placebos before, and the more barriers you put in the more difficulty there would have been to enroll such a large number of people in the U.S."
In April 2015, the company initiated additional analyses of the studies, and in July 2015, Nymox said phase III long-term extension studies of fexapotide in BPH met the pre-specified primary endpoint of statistically significant improvement in long-term symptomatic benefit over placebo. Nymox also said at that time that it planned to proceed with regulatory filings.
A month later, Nymox reported that it received formal approvals to change its domicile to the Bahamas.
In August of this year, Nymox reported findings from a phase III long-term cancer incidence analysis in which subjects received fexapotide or placebo to treat BPH symptoms and were followed for up to seven years (median of five years) following treatment. The study analyzed cases of prostate cancer that were subsequently diagnosed.
The expected rate of new prostate cancer cases in the U.S. general male population of middle-age and elderly men was in the range of 5 percent to 20 percent after seven years, according to Nymox. But data from the fexapotide study, which enrolled a similar population of middle age and elderly men with BPH, suggested a subsequent prostate cancer incidence of just 1.3 percent among those treated with the study drug, which Nymox called a statistically significant difference, without providing additional details.
Nymox also reported in August that a long-term, blinded, placebo crossover group study showed an 82 percent to 95 percent reduction in the number of patients who required surgery after they crossed over to fexapotide treatment compared to patients who crossed over to conventional, approved BPH treatments (p<0.0001). In that study, long-term outcomes were determined in 391 patients who were given double-blind placebo injections, followed by crossover to other treatments at the discretion of each patient. The number of blinded placebo patients who subsequently received surgical treatment for BPH symptoms during the following two to three years was then prospectively analyzed.
As of June 30, Nymox reported cash and receivables, including tax credits receivable, of approximately $327,000, compared with approximately $653,000 as of Dec. 31, 2015.
On Tuesday, investors gave the company a vote of confidence, lifting shares (NASDAQ:NYMX) in heavy trading by 41 cents, or 12.5 percent, to close at $3.69.