BioWorld International Correspondent

Shares in Jerini AG dropped sharply on mixed news emanating from two Phase III trials of its lead product, Icatibant, in development for hereditary angioedema (HAE).

The product, a synthetic peptide antagonist of the bradykinin B2 receptor, reached the primary endpoint in the FAST-2 study, which compared its efficacy with that of tranexamic acid. However, it failed to attain the primary endpoint of a placebo-controlled study, known as FAST-1, although the Berlin-based company said the results were "clinically relevant." Results from FAST-2 are sufficient for a European filing, whereas the FDA requires data from the two pivotal trials for its evaluation.

The company's share price dropped almost 28 percent Friday on release of the news, closing at €3.64 (US$4.61), down €1.01 from Thursday.

In FAST-2, a 74-patient study conducted in Europe and Israel, median time to onset of symptom relief was two hours for Icatibant vs. 12 hours for tranexamic acid, as measured by a visual analogue scale. The result was statistically significant (p<0.001).

In FAST-1, a 56-patient trial conducted in the U.S., Canada, Argentina and Australia, the primary endpoint of median time to onset of symptom relief was 2.5 hours for Icatibant vs. 4.6 hours for placebo, a result that was not statistically significant (p=0.131).

"We had an unexpected high placebo effect in patients with abdominal pain," said Jerini CEO Jens Schneider-Mergener on a conference call. "Also, the variability in the FAST-1 study was higher compared to the FAST-2 study."

Schneider-Mergener declined to elaborate further on the latter point. "This is some very interesting data we have to discuss with the FDA," he told BioWorld International.

Several secondary endpoints in each study were met with statistical significance in favor of Icatibant, and a combined analysis of the two studies provided further evidence in support of its efficacy.

Jerini plans to apply for expedited reviews at both the FDA and the London-based European Medicines Agency, and it will commence its regulatory submissions by year end, with the aim of achieving product launch by 2007. Schneider-Mergener said the drug could be approved in the U.S. on the basis of the secondary endpoints in FAST-1. "Obviously the FDA has the last say, but a second trial would not make any difference, would not add any data," he said.

"That's the worst case scenario - that they would have to do another trial," Daniel Wendorff, analyst at WestLB AG, in Dusseldorf, Germany, told BioWorld International. Upcoming discussions between Jerini and the FDA will determine what happens next and Wendorff said there might be "some clarity within four to eight weeks." In the meantime, he has trimmed his target price on the stock, from €5.10 to €4.40. The latter price conservatively excludes any potential sales from the North American market, he said.

The news bolstered Cambridge, Mass.-based Dyax Corp., whose rival product, DX-88, is due for another clinical trial at the request of the FDA. The company's share price gained 18.5 percent following release of the news, closing at $3.40.

For the moment, however, Wendorff still predicts that Icatibant will become the market leader in HAE, a condition characterized by acute episodes of painful and potentially life-threatening swelling of the skin or mucosa. He forecasts that it will gain a 50 percent market share, whereas DX-88 will gain 30 percent. Icatibant is more convenient to take, he said, as it is available in pre-filled syringes, whereas DX-88, a small protein inhibitor of the enzyme kallikrein, is not stable at room temperature.

The rest of the market, he said, will be split between recombinant C1 inhibitor, which Leiden, the Netherlands-based Pharming Group NV is developing, and a plasma-derived C1 inhibitor in development at New York-based Lev Pharmaceuticals Inc. "If the FDA does require Jerini to undertake another trial, I would have to reconsider the whole situation," he said.