Auxilium Pharmaceuticals was founded in 1999 to develop and market pharmaceutical products that focus on urology and sexual health. The company's focus is on treating diseases and conditions that accompany aging. The premise is simple: "Many of the serious health problems that affect men and women as they age can be treated successfully. In areas such as urologic and sexual health, energy, mood, muscle mass and bone density, Auxilium is working to develop therapies designed to restore lost function and help people live healthier lives." The company has one Food and Drug Administration (FDA) approved product currently on the market for hypogonadism, called Testim (1% testosterone). Auxilium is also working on clinical and pre-clinical programs for Dupuytren's Contracture, Peyronie's disease, frozen shoulder syndrome, overactive bladder, and androgen replacement. Auxilium Pharmaceuticals is located in Malvern, PA, and employs about 269 professionals.
Testim Gaining Share
Testim, a 1% testosterone gel, is the only approved product at Auxilium Pharmaceuticals. It was approved in October 2002 and launched in February 2003. The product is indicated for the treatment of hypogonadism. Hypogonadism, or a low testosterone level, is a disorder that affects approximately 20% of the U.S. male population over age 50. Symptoms include low energy levels, low sex drive, loss of muscle mass, loss of bone density, increased body fat, sexual dysfunction, and mild depression. Auxilium estimates that only 5% of affected men actively seek treatment. Testim utilizes a proprietary transdermal drug delivery technology developed by Bentley Pharmaceuticals. Testim gel is applied to the shoulders and upper arms every 24 hours. Roughly 10% of the solution is absorbed into circulation. Based on impressive phase III data, roughly 75% of Testim users will achieve normal serum testosterone levels in 90 days. Testim users should see improved sexual performance, an increase in lean body mass (muscle), and a decrease in total body fat (both percent and weight).
Data presented at the annual meeting of the American Urological Association (AUA) in May 2007 showed that Testim demonstrated an improvement in symptoms of decreased libido, energy levels and erectile function in a majority of patients who were initially unresponsive to AndroGel, Testim's main competitor in the topical testosterone market. This data was also recently published in the International Journal of Impotence Research in October 2007. Auxilium's specialized sales force has been out marketing this message for the past several months. It looks like physicians are starting to pay attention, as market share for the product eclipsed 20% to 20.7% at the end of the third quarter based on IMS prescriptions. This is up from 19.8% at the end of the second quarter 2007 and 18.2% at the end of the third quarter 2006. Market share in the highest prescribing faction of urologists is roughly 39%, demonstrating that Auxilium's message is clearly getting through. Sales in the third quarter 2007 totaled $26.2 million, an increase of 49% over the third quarter in 2006. For the full year we see sales of $94.5 million, in-line with management's guidance of $92 96 million.
Testim competes directly with AndroGel, a 1% testosterone gel sold by Solvay Pharmaceuticals worldwide. AndroGel posted sales of approximately $360 million in 2006. Given our belief that the size of the topical testosterone market is roughly $500 million, Testim will have to continue to take market share from AndroGel in the coming quarters to continue its impressive growth. We believe that Testim is superior to AndroGel in terms of absorption this was clearly demonstrated by the data presented at AUA in May 2007. Unfortunately, Solvay recently teamed up with two generic manufacturers in Watson and Par Pharmaceuticals for co-promotion. Par's branded sales force will promote AndroGel to additional physicians in existing as well as new geographical regions, and Watson's specialty force will co-promote AndroGel to urologists. In total there around over 600 reps that promote AndroGel vs. Auxilium's specialty sales force of around 150 reps. This enhanced effort by Solvay, as well as a lower price for the drug, may ultimately keep Auxilium's market share gains at a minimum.
One final concern we have is potential generic alternatives. AndroGel was the subject of active patent challenges by both Watson and Par before Solvay agreed to a co-promotion. Generic 1% testosterone would be a major impediment to Testim growth based on price. Auxilium management continues to make progress on protecting its intellectual property (IP) by filing a new application for protection earlier this year. In September, the U.S. Patent and Trademark Office issued a Notice of Allowance' for the pending U.S. patent application covering the Testim composition. We expect the patent will issue in late 2007 or early 2008 and could protect Testim into 2023.
Xiaflex Back On Track
Xiaflex (formerly AA-4500), is an injectable enzyme (clostridial collagenase) undergoing several clinical programs. The most advanced program is for Dupuytren's Contracture. Dupuytren's Contracture is a condition that affects the connective tissue in the palm known as palmar fascia. Dupuytren's disease often limits movement of the fingers by an abnormal thickening of the palm. Severe cases are associated with the loss of full extension of the involved finger because of a cord that stretches from the palm to the fingers is contracted. Hands affected by Dupuytren's Contracture are usually deformed but the disease does not cause pain. The cause is not yet known and there are no known cures. Auxilium believes that injecting Xiaflex may help to soften or reduce the cord in the hand.
In November 2006, Auxilium started dosing patients for a pivotal phase III trial for Dupuytren's Contracture. The company also initiated an ex-U.S. study (n=60) for Dupuytren's Contracture in Australia and Switzerland. However, in early December 2006, Auxilium announced the temporary suspension of phase III trials for Dupuytren's due to a manufacturing issue (meltback of the lyophilized cake). On the second quarter 2007 conference call, Auxilium unblinded the results from the suspended phase III trials. A total of 30 patients were treated 22 received Xiaflex and 8 received placebo. The data indicate that 64% (14 of the 22) of the patients injected with Xiaflex achieved clinical success defined as reduction of the contracture to 0 5 degrees of normal versus 0% for the placebo. The company had earlier presented full results from a pivotal efficacy program in February 2007 at the annual meeting of the American Association of Orthopedic Surgeons (AAOS). The data demonstrated 91% of patients treated with Xiaflex achieved the primary endpoint of reduced contracture compared to 0% for the placebo arm. Results from the open-label phase (in which patients had additional joints treated with Xiaflex) showed that 88% of Metacarpophalangeal (MP) joints and 68% of Proximal Interphalangeal (PIP) joints were fully corrected. Data from this study was published in the July 2007 issue of the Journal of Hand Surgery.
The manufacturing issues have been worked out and in August 2007 the company received FDA clearance for the resumption of phase III trials with Xiaflex. The company is conducting two trials one in the U.S. and the other in Australia. The U.S. CORD-I (Collagenase Option for Reducing Dupuytren's) study is a double-blind, placebo-controlled study that has enrolled approximately 216 patients the primary endpoint is to see whether Xiaflex can reduce the contracture angle of the primary joint to within 0 to 5 degrees of normal after up to three injections. Once this study is completed, patients will be enrolled in a separate open label extension study which will form the basis of 12-month follow-up information that will be submitted to the FDA as part of the Biological License Application (BLA) filing. The Australian CORD-II study (n=60) is similar to the U.S. study only on a smaller scale. The company completed enrollment on December 17, 2007 for both programs. Top-line results from this trial could be available in the second quarter of 2008. Auxilium is also planning to conduct an open-label trial outside the U.S. with about 340 patients this study will be conducted in Australia and Switzerland and might potentially expand into the E.U. The company is currently guiding towards a BLA filing in early 2009. If approved, Auxilium could be in position to launch early in 2010.
Manufacturing plans are also back on tract at the company's Horsham facility. Management expects to complete 10 test batches for the BLA submission before the end of the year. Once complete, Auxilium will shut down the facility to make minor adjustments before they begin manufacturing for commercial supply.
The next indication for Xiaflex is Peyronie's disease (PD). PD is the development of scar tissue on the shaft of the penis. It causes pain during erection or sexual intercourse. PD usually occurs in men over the age of 50, as a result of direct trauma to the penis. The company believes that injecting Xiaflex into the affected area of the penis may soften or reduce the scar tissue. Since patients with PD have little other option besides surgery, Xiaflex has been granted exclusivity through the FDA s "orphan drug" program. In October 2006, Auxilium reported positive results from two phase II trials which showed that Xiaflex is effective and generally well-tolerated in treating patients with PD. Results showed that 89% of patients receiving a three-treatment series of three injections each achieved clinical success, which was defined as change from baseline in deviation angle of at least 25%. Auxilium is currently working on the animal study requested by the FDA. Results from this study should be out in the first half of 2008. Assuming no issues on toxicology or safety, the company should be in position to initiate a phase IIb trial for Peyronie's in mid 2008.
In addition to the above two indications, Auxilium is also evaluating Xiaflex for another indication frozen shoulder syndrome. Frozen shoulder syndrome is a disorder of diminished shoulder motion and almost 3% of people, especially women, develop this problem over their lifetime. A phase II trial conducted with Xiaflex showed that a local injection of the drug was well-tolerated and that it may be effective in the treatment of frozen shoulder syndrome. Additional studies will have to be conducted in order to determine the optimal dosage and regimen. We expect to see some results on this indication shortly.
Transmucosal Film An Early Look
In February 2005, Auxilium licensed an oral drug delivery system from Formulation Technologies (PharmaForm). The transmucosal film adheres to the upper gum to deliver medication in a more effective administration. Auxilium believes that this creates lower incidence of side effects and better absorption than current market offerings. Auxilium is using this technology in its development of candidates for overactive bladder and androgen replacement therapy. The company completed an initial phase I study on the overactive bladder transmucosal film candidate (AA4010), and will be moving the candidate into phase II studies. We believe Auxilium might seek a partner for the further development of this candidate. In addition to AA4010, the company has two pain product candidates which are being developed using the transmucosal film technology. These candidates are currently in the pre-clinical phase of development for the management of pain.
Pipeline Graph Future Heavily Dependent on Xiaflex