Staff Writer

Aderis Pharmaceuticals Inc. said Phase II results showed that selodenoson slows the ventricular rate among atrial fibrillation patients.

The findings were reported at the American Heart Association meeting in Orlando, Fla. The 63-patient, double-blinded, placebo-controlled trial demonstrated that six different doses of the selective adenosine A1 agonist demonstrated a statistically and clinically significant decrease in ventricular rate, compared to placebo.

"I think it is becoming very apparent through all the meetings that slowing the rate for a vast majority of patients is better than rhythm control," said William Wheeler, Aderis' vice president and chief medical officer. "Most of the rhythm control agents have side effects."

In the trial, patients were randomized to receive placebo or intravenous selodenoson at 2, 4, 6, 8, 10 or 12 mcg/kg doses as a 15-minute infusion. The heart rate was reduced by all doses at five, 15 and 30 minutes after the infusion began and there were neither significant changes in systolic or diastolic blood pressure nor any serious adverse events.

"In the acute setting with an intravenous drug like what we have, I think it's very important to get rate down smoothly, rapidly and without problems of dropping blood pressure," Wheeler told BioWorld Today. "Current medications typically used for slowing a heart rate - calcium channel blockers and beta blockers - can cause hypertension even before they control heart rate."

Hopkinton, Mass.-based Aderis is developing the product in partnership with Fujisawa Healthcare Inc. to control heart rate in atrial fibrillation patients while minimizing changes in blood pressure or decreases in heart function.

Intravenous selodenoson is being developed for in-hospital use, while a sustained-release oral dosage form is being developed for chronic disease management on an outpatient basis. Deerfield, Ill.-based Fujisawa is developing the intravenous dosage form for U.S. and Canadian markets, while Aderis retains all other rights to the product. Wheeler said the oral formulation remains in a Phase I program as the company continues to plan follow-on pharmacokinetic studies.

The meeting is serving as a forum to present findings on another cardiovascular offering from Aderis, an adenosine A2A agonist called Binodenoson being developed as a pharmacologic stress agent in partnership with King Pharmaceuticals Inc. Wheeler said Bristol, Tenn.-based King would report findings today showing that their drug is equivalent to Adenoscan in diagnosing coronary artery disease and has a better side-effect profile. The product is scheduled to enter a Phase III program next month.

Elsewhere in its pipeline, Aderis' lead product is Rotigotine CDF, a dopamine agonist delivered by way of a once-daily patch for Parkinson's disease. Wheeler said the product provides steady blood levels to patients throughout the day. Aderis' development partner, Monheim, Germany-based Schwarz Pharma AG, said positive results from two recently completed Phase III studies would be included in U.S. and European regulatory filings, scheduled for the third quarter of next year.

Founded in 1994, the privately held company recently pulled an initial public offering for the second time in its corporate history. The company first filed for its IPO in January 2002, but withdrew the offering eight months later. In August, Aderis registered again before officially withdrawing its plans this month. (See BioWorld Today, Oct. 30, 2003.)

In other news from the meeting:

• Avant Immunotherapeutics Inc., of Needham, Mass., said Phase II data demonstrated that TP10 (sCR1) inhibited harmful complement-mediated inflammation in men undergoing cardiac surgery involving cardiopulmonary bypass, leading to a significant reduction in post-surgical deaths and heart attacks. Results from the placebo-controlled, double-blinded, 564-patient study, reported by investigators from the Boston University School of Medicine, also showed that TP10 significantly inhibited complement activation in all treated patients compared to placebo for up to three days after surgery. Avant's stock (NASDAQ:AVAN) gained 29 cents Tuesday, or 12.2 percent, to close at $2.67.

• EPIX Medical Inc., of Cambridge, Mass., reported Phase II findings showing that MS-325 appears safe and well tolerated in renally impaired patients, including those requiring dialysis, and the contrast agent had no adverse effect on renal function. The product, which is being developed in partnership with Schering AG, of Berlin, is designed for vascular imaging with magnetic resonance angiography and has completed four Phase III trials. EPIX said it would submit the new drug application to the FDA before the end of the year.

• Genaissance Pharmaceuticals Inc., of New Haven, Conn., reported clinical data describing associations between genetic markers (HAP markers) and response to treatment with the statin class of drugs. The company confirmed an association between HAP Markers in the gene apolipoprotein E and levels of C-reactive protein. Also, Genaissance described an association between HAP Markers in the gene P-selectin and changes in the level of HDL-cholesterol in response to statin therapy.

• Genzyme Corp., of Cambridge, Mass., said preliminary Phase I results suggested that its gene therapy was bioactive after treatment resulted in complete healing of leg ulcers in several critical limb ischemia patients, with an apparent trend in favor of the higher doses. Genzyme's therapy, which uses an engineered form of the HIF-1alpha gene, is designed to promote new blood vessel growth and improve circulation in patients' limbs. The limb survival rate for treated patients was 67 percent vs. an expected rate of 50 percent to 65 percent at one year. Investigators reported that Ad2/HIF-1alpha/VP16 appears safe, with no treatment-related serious adverse events observed.

• Scios Inc., a unit of Johnson & Johnson, of New Brunswick, N.J., said an investigator-sponsored study pointed to an association between the use of Natrecor (nesiritide) and fewer complications, significantly less health care resource use, and lower hospital costs for patients with acute decompensated heart failure. A net cost savings of $1,446 per patient was demonstrated with acute heart failure patients who received nesiritide, compared to patients who did not receive the drug. The savings included nesiritide's cost.

• The Medicines Co., of Parsippany, N.J., reported one-year mortality results of the REPLACE-2 coronary angioplasty trial, showing that 1.9 percent of patients randomized to Angiomax (bivalirudin) died vs. 2.5 percent of patients randomized to heparin with platelet glycoprotein IIb/IIIa inhibitors (p=0.162). The 0.6 percent absolute difference in mortality rates between the two trial arms compares to results reported after six months of follow-up, when the absolute difference was 0.4 percent in favor of Angiomax (p=0.148). The greatest mortality differences were observed in elderly patients, in which the difference was 3.3 percent (p=0.039), and those at risk of imminent heart attack, in which the difference was 1.6 percent (p=0.016).