By Lisa Seachrist
WASHINGTON — Alexion Pharmaceuticals Inc. and Axys Pharmaceuticals Inc. disclosed positive Phase II trial results for an inflammation inhibitor and an asthma treatment, respectively. Both companies intend to move their drug candidates into larger Phase II studies.
New Haven, Conn.-based Alexion reported its lead compound, 5G1.1-SC, a C5 complement inhibitor, reduced the incidence of cardiac damage, cognitive deficits and blood loss in patients undergoing coronary artery bypass graft (CABG) surgery in Phase I/II and Phase IIa studies.
"We've previously shown that the drug potently blocks complement activity," said Leonard Bell, president and CEO of Alexion. "I think the data really suggest strongly that blocking the complement cascade with a C5 inhibitor significantly reduces organ damage. Obviously, we are enthused."
C5 complement is at the midpoint of the complement cascade. 5G1.1-SC is a humanized, single-chain, short-acting antibody designed to stall potentially damaging inflammation during procedures that require the use of a heart-lung bypass machine.
Because bypass procedures leave the heart and lungs without blood flow and significantly reduce blood flow to the rest of the body, patients undergoing them can suffer heart damage. In addition, CABG surgery carries the risk of small emboli - pieces of fat, artery, calcium and air bubbles - traveling to the brain, blocking blood flow and causing cognitive deficits. Many patients also suffer postoperative bleeding.
In its studies, Alexion tested 35 CABG patients. Researchers gave each patient a single bolus of one of four doses of 5G1.1-SC — 0.2 milligram per kilogram, 0.5 milligrams per kilogram, 1.0 milligram per kilogram or 2.0 milligrams per kilogram — or a placebo.
Patients who received the 2.0 milligram per kilogram dose of 5G1.1-SC had a 40 percent reduction in CK-MB, a measure of an enzyme that is released into the bloodstream when heart muscle dies, compared with placebo patients. Treated patients achieved an 80 percent reduction in cognitive deficits compared to placebo patients. The drug also reduced postoperative bleeding by approximately 400 milliliters compared with placebo patients.
Preliminary Studies Gave Reasons To Continue
"These are preliminary studies that served as a proof of principle that the drug can provide a reduction in morbidity," Bell said. "This is a step-wise process, and our next step is to expand to a larger Phase II trial to give us an idea how effective the drug is before we would move on to a pivotal trial. The news today warrants a further investment into this drug and indication."
Alexion is developing a longer-acting, double-chain, humanized antibody, 5G1.1, as a treatment for rheumatoid arthritis and lupus and plans to begin enrolling patients in clinical trials in May.
Axys, of South San Francisco, disclosed final results of its Phase IIa clinical trial of APC-366, a tryptase inhibitor for the treatment of asthma, in 16 patients. Inhaling nebulized APC-366 reduced the severity of allergen-induced late airway response (a measure of inflammation in the lungs) by 33 percent.
The participants in the trial had mild asthma and received three doses of APC-366 per day. On the fourth day, after the tenth dose, patients in the double-blind crossover study were challenged with an inhaled allergen.
Those receiving APC-366 showed less lung inflammation with 21 percent more lung function than those on placebo. Both measures were highly statistically significant.
"We are moving forward with this product," said David Gennarelli, manager of investor relations for Axys. "We intend to file an [investigational new drug application] by the end of the second quarter. Hopefully, we will enter into our Phase IIb trial by the end of the year."
The Phase IIb trial will comprise 400 to 600 patients and use a reformulated version of APC-366, tested as a dry powder using an inhaler designed by development partner Bayer AG, of Leverkusen, Germany.
Axys also will test how quickly the drug arrests inflammation. An earlier Phase IIa trial of the drug that attempted to quell bronchial hyperresponsiveness in four days failed to reach statistical significance. Steroids typically take six weeks to work on the condition.
"We set a very high bar in that trial," Gennarelli said. "We didn't reach statistical significance, but two-thirds of the patients improved, so we saw a trend."
Axys' stock (NASDAQ:AXPH) closed at $7.375 per share, unchanged. Alexion's shares (NASDAQ: ALXN) ended the day at $13.75, down $0.375. *