BioWorld International Correspondent

Spurred on by positive topline data from a pivotal Phase III clinical trial of the chronic hand dermatitis treatment alitretinoin (formerly BAL4079), investors in Basilea Pharmaceutica AG pushed the company's share price to close at an all-time high of CHF270 (US$218.46) on the Swiss Stock Exchange in Zurich Monday, a gain of CHF12 on its previous close.

The Phase III clinical study, which was conducted in centers across Europe and in Canada, met its primary endpoint of clearing or almost clearing the hands of patients with severe refractory chronic hand dermatitis, who were unresponsive to topically applied steroids.

The 24-week trial recruited 1,032 patients, who were randomly assigned to one of three treatment arms: 30 mg alitretinoin (n=409 ); 10mg alitretinoin (n=418); or placebo (n=205). A dose-dependent response to the therapy was evident in the trial data, Basilea CEO Anthony Man said on a conference call.

Forty-eight percent of patients receiving the higher dose were reported as having their hands cleared or nearly cleared of lesions, as measured by the physicians global assessment scoring method. The equivalent statistics for the lower-dose group and the placebo group were 28 percent and 17 percent, respectively.

Data on secondary endpoints, including time to response and time to relapse, as well as data on quality-of-life measures will be made available later this year. "There are still patients on study so we haven't completed the analysis," Man said.

The compound's safety profile was consistent with what was observed in a previous Phase II clinical trial. The most common adverse events were headache and elevated blood lipids, both of which were dose-dependent and reversible, the company said.

Some 20 percent of the high-dose group reported headache, while 11 percent of the low-dose group did so. Just 6 per cent of the placebo group reported headache. However, Man said, only 4 percent of the high-dose group discontinued treatment because of this problem.

Basel, Switzerland-based Basilea aims to file for approval of both doses in Europe and Canada during the second half of this year, when the secondary endpoint analysis will be completed. By then it also will have completed an open-label safety study involving around 200 patients and a re-treatment trial involving 300 patients. The topline data from the latter study will become available in the second quarter, Man said. The company also plans to open discussions with the FDA in the second half of the year, to determine the appropriate course for seeking approval in the U.S.

Basilea estimates that there are around 1 million patients in Europe and North America with severe chronic hand dermatitis who do not respond to currently approved treatments. The drug could be on the market in one to two years but the company has not disclosed any sales forecasts. "The pricing for this compound will be based on the measurable economic benefit that is resulting from the clinical benefit," Nicholas Benedict, head of commercial strategy and operations at Basilea, said on the conference call.

As well as imposing direct health care costs, the condition also leads to additional economic burdens through absenteeism. "A very significant proportion of the severe refractory chronic hand dermatitis patients have to change jobs," Benedict said.

The company plans initially to promote the product through the sales force it is building to promote its broad-spectrum cephalosporin antibiotic Ceftobiprole, which is also nearing the market. Basilea is co-promoting that product with Cilag GmbH International, a subsidiary of Johnson & Johnson Co., of New Brunswick, N.J.

Ceftobiprole has attracted blockbuster forecasts from analysts. Alitretinoin, a Vitamin A derivative, has a more modest potential, however. "We have peak sales estimates of only CHF300 million (US$242 million) so far," analyst Markus Metzger at Vontobel Securities AG, of Cologne, Germany, told BioWorld International.

"We have not seen the secondary endpoints and the re-treatment study so far." The product also has teratogenic potential so women of child-bearing age need to avoid pregnancy while taking the therapy. "The safety profile is very important," Metzger said.

Basilea shed some of its gains during trading on Tuesday morning, dropping back to CHF266 by lunchtime, which values the company at CHF2.05 billion. "From my estimates , I would already say it's pretty stretched in terms of fundamental evaluation," Metzger said, although he is upbeat about its longterm prospects. "It's a great company. They are very diversified. It's one of the companies that will make it as an independent entity in the long run."