Australian company, Acrux, today announced positive results from a Phase III trial evaluating the safety and efficacy of AXIRON™ in 155 men with testosterone deficiency (hypogonadism), across 26 sites in six countries.
AXIRON™ is applied to the underarm using a unique “no-touch” applicator. Upon approval, AXIRON™ would be the first and only pharmaceutical product applied to the armpit - in much the same way as an antiperspirant. As well as existing patents that protect AXIRON™ to 2017, Acrux has a new patent that, when granted, will extend protection of this novel, class-leading feature until 2026.
Phase III trial results
The trial met its primary endpoint by demonstrating that after four months of treatment with AXIRON™, 84 percent of subjects achieved average blood levels of testosterone within the normal range, exceeding the requirement of 75 percent that was agreed upon by the U.S. Food and Drug Administration (FDA).
After only two weeks of treatment, it was found that 76 percent of subjects had average blood levels of testosterone within the normal range.
The average testosterone level for the responder group after 120 days treatment with AXIRON™ was 504ng/dl (the normal range being 300-1,050ng/dl). The average baseline testosterone level in subjects prior to treatment was 190ng/dl.
Four different dose levels of AXIRON™ were tested, and the trial demonstrated that the optimum dose for 75 percent of subjects was 60mg testosterone per day, equivalent to one single application of AXIRON™ to each armpit.
Subjects were permitted to use an underarm deodorant or antiperspirant during the trial. More than half of the men continued to apply an underarm deodorant or antiperspirant as part of their daily routine, and an analysis of these subgroups showed that this had no impact on the efficacy of AXIRON™ treatment.
Analysis of mood, sexual desire, sexual activity and sexual performance before and after four months of treatment showed significant improvement from baseline across all measures.
There were no serious adverse events related to treatment with AXIRON™ and no adverse trends were identified with the biochemical safety measures, including prostate specific antigen, haematocrit, and the ratio of dihydrotestosterone to testosterone.
Fifty-two men continued treatment for an additional two months specifically to monitor skin safety with six months of continuous use. Eight subjects reported some form of transient application site reaction during the main treatment phase of four months; however, these reported events were all mild or moderate and resolved quickly without any intervention. No patient withdrew due to a skin reaction.
“In terms of the proportion of responders to testosterone replacement using AXIRON™, the pharmacokinetic parameters and the response from this multi-center clinical trial, the results are very exciting and precisely what we had hoped to see,” commented lead investigator Professor Christina Wang, MD, at Los Angeles Biomedical Research Institute and Professor of Medicine at David Geffen School of Medicine at UCLA. “The post-treatment changes demonstrated positive responses in sexual desire, sexual activity, mood and general well-being, underpinning the patient- reported benefits of this treatment. Patient compliance and acceptance of the unique no-touch axilla application technique was very good, as evidenced by the high completer rate,” added Professor Wang.
Earlier this month, Acrux announced it had held a pre-NDA meeting with the FDA in Washington, DC and the FDA had agreed Acrux may proceed to file a New Drug Application (NDA) in the United States, which Acrux is targeting for the end of 2009.
Acrux has already received strong interest from a number of potential marketing partners for AXIRON™. Following release of the Phase III trial results, formal partnering discussions with interested parties will be progressed in October 2009.
If approved by the FDA, market entry for AXIRON™ could occur in early 2011, and may play an important role in the treatment of patients living with hypogonadism. Based on IMS data, global sales in this market for the year to March 2009 exceeded U.S. $1 billion for the first time, and sales in the U.S. market grew by more than 20 percent. Sales of testosterone gels in the U.S. grew to U.S. $0.7 billion for the year to March 2009.
Last year Acrux published results from market research conducted in both patients and physicians in the USA, in which two thirds of patients confirmed that they would prefer AXIRON™ to their existing gel treatment and 87 percent of physicians said that they would offer AXIRON™ to their patients that currently use gels. Importantly, 94 percent of patients who tried AXIRON™ rated it better than the testosterone gels in its ability to reduce the risk of transference of testosterone to others. In addition, 92 percent of physicians surveyed who prescribe gels as first line therapy rated AXIRON™ as very good or excellent in its ability to reduce the risk of transference to others when compared to the gels.
“We are excited by the AXIRON™ Phase III trial results and are now well positioned to submit our NDA by the end of 2009,” said Dr. Richard Treagus, CEO and Managing Director of Acrux. “These results, along with our recent meeting with the FDA, place us in a strong position as we initiate a process to select marketing partners for what is a unique testosterone delivery system that we believe will be a patient preferred treatment for hypogonadal men,” he said.
About AXIRON™ (testosterone solution) 2%
Testosterone deficiency in men (hypogonadism) is associated with a number of symptoms including lethargy, depression, reduced libido and decrease in muscle mass and bone density. Estimates of men over 50 years of age having testosterone levels below the normal healthy range vary from 10 percent to 39 percent1. However, in the majority of men this remains undiagnosed, with only around five percent to 10 percent of those with the condition receiving treatment. With a high incidence rate and low but growing treatment rates, the male testosterone deficiency market will remain an attractive commercial opportunity. AXIRON™ has been designed to overcome the significant issues and drawbacks associated with the current gel treatments. Large volumes of gel are applied by hand and rubbed on to the abdomen, shoulders or arms. They are considered messy, sticky, slow-drying and may have an unpleasant odour to some patients. One of the biggest drawbacks is the risk of transference to other people through contact with the application site or from residue left on the hands following application. AXIRON™ is a faster-drying and pleasant smelling solution that is applied to the armpits once daily, using a convenient and ergonomic “no-touch” applicator designed in Australia. The armpit is a unique application site for transdermal drug delivery and it offers significant advantages to the patient in terms of convenience and may have a lower risk of transference from patient to others. A factsheet on AXIRON™ is available for download at www.acrux.com.au.
About Acrux (ASX: ACR) - www.acrux.com.au
1 Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762-769