On the same day it revised guidance, Auxilium Pharmaceuticals Inc. reported positive data from an initial Phase III study of AA4500, an injectable enzyme product for Dupuytren's disease.
The top-line results showed that local injections of AA4500 were highly effective in treating the condition, which also is called Dupuytren's contracture. The affliction impairs the ability to straighten and move hand joints due to a thickening and shortening of the normal ligaments of the palm and digits, caused by excess scar tissue or collagen. The investigational molecule, a combination of collagenase subsets, essentially digests the collagen formed by the genetic condition.
"We're really excited about this," said James Fickenscher, Auxilium's chief financial officer. "We think that this is a market-changing and company-changing product for us."
AA4500 produced a 91 percent success rate on the study's primary endpoint: less than 5 degrees of contracture in treated joints, the proximal intra-phalangeal (PIP) joint and metacarpal phalangeal (MP) joint, after up to three injections. A contracture reduction to less than 5 degrees essentially allows a hand to lie flat. That compared to a nonexistent response rate in the placebo group (p<0.001).
Notably, 70 percent of patients achieved therapeutic success after just a single injection of AA4500. There was an average of 1.4 injections per joint.
At present, surgery remains the only option for treating the condition, which primarily affects Caucasians of Northern European descent. But just "a fairly small percentage" of the estimated 500,000 Dupuytren's patients who visit orthopedic surgeons annually choose surgery, Fickenscher told BioWorld Today. It is delicate and lengthy, as is patient rehabilitation.
While surgery proves effective in the short term, eventually the collagen nodes return, and patients find themselves in the same predicament a few years later.
Fickenscher conceded that AA4500-treated patients also would have to deal with recurrences, given that the product does not treat the underlying cause of Dupuytren's contracture, although Auxilium does not know how quickly the disease would return because long-term data are not available yet. But he noted that the return of regular hand movements within three weeks, by way of a much less invasive treatment, is amenable to both patients and physicians who have reported interest in avoiding complications inherent in surgery.
"We think it will be better for the patient," Fickenscher said. "It will be better for the health care system because the surgical procedure's cost is pretty significant, while at the same time, we ought to get a pretty good return for our shareholders by pricing this as a premium product."
He declined to forecast AA4500's cost, but noted that surgery expenses range between $10,000 and $15,000. No other therapeutics are being developed in the space, Fickenscher added, though he said some physicians have developed an invasive technique to break up the scar tissue nodes with a needle.
The double-blinded trial included 35 patients, 23 of whom were randomized to receive up to three injections of AA4500. In addition to the positive efficacy findings, the product's safety and tolerability profile also proved satisfactory: There were no nerve, vascular or tendon injuries associated with AA4500 administration during the year-long trial, nor were any such problems observed in a follow-up evaluation of 19 patients who received up to five injections of AA4500. Those results were consistent with Phase II findings published in The Journal of Hand Surgery.
A second Phase III trial is scheduled to begin in the second half of this year as part of the product's pivotal program. It will include up to three injections of AA4500, dosed monthly, and it should be completed relatively quickly due to heightened patient interest. Aside from adding to the number of participants, the coming study's protocol should look similar to this first Phase III trial.
"Let's not try to recreate the wheel every time," Fickenscher said. "This is the relevant endpoint, we think. We've had discussions with the FDA, and although there are some things that they have asked us to do, it is essentially a very similar design."
Auxilium has a license to AA4500 from BioSpecifics Technologies Corp., which has evaluated its use in more than 1,000 patients to date in a range of indications involving excess collagen. That prior testing would add supportive safety data for an eventual biologics license application to be filed with the FDA.
Fickenscher said the product could reach the market by 2008, adding that Auxilium plans to field a small sales force for its commercialization.
The specialty pharmaceutical company, which will sponsor and monitor the coming study, took an interest in AA4500 because of its traditional focus in urology. Searches for products to treat Peyronie's disease, a condition in which excess scar tissue distorts the shape of a penis, led to BioSpecifics Technologies, of Lynbrook, N.Y.
The licensing arrangement between the firms provided Auxilium worldwide rights to AA4500 in exchange for milestone payments and eventually low-double-digit royalties. Also, BioSpecifics Technologies receives a fee every time it supplies data on additional viable indications that Auxilium decides to pursue.
"What we're talking about doing with this drug is scar remodeling," Fickenscher said, adding that "there are a number of follow-on indications for AA4500 that are pretty exciting." In addition to Dupuytren's contracture, the company expects further development for Peyronie's disease and a condition in which patients' shoulder movements are restricted due to scar tissue buildups, at the very least.
Auxilium plans to pursue sources of commercial supply for AA4500 beyond what is available from its current contract manufacturer. With such growing development costs on the horizon, the company changed its guidance for the rest of the fiscal year.
As a result of a higher manufacturing expense with its current supplier, Auxilium expects this year's R&D expenditure to increase, correlating to a wider full-year loss. Instead of $38 million, that loss would range between $40 million and $43 million. Other financial estimates should remain consistent with previously provided ranges, including revenues of $64 million to $68 million.
On Wednesday, Auxilium's stock (NASDAQ:AUXL) slipped 10 cents to $8.80.