Nuvelo Inc announced completion of enrolment of its phase 2 trial with lead product candidate, alfimeprase, showing that alfimeprase restored blood flow in the limbs of patients with acute peripheral arterial occlusion (PAO) in four hours or less, a company release said.
"Most thrombolytic agents require a prolonged infusion of 24 to 36 hours in patients with acute PAO," stated Dr Steven R Deitcher, vice president medical affairs for Nuvelo. "This trial showed that we can rapidly restore arterial blood flow to these patients with alfimeprase," he added.
While the full data set is still being analysed, the preliminary data suggest that there was a dose response, increasing the rate of restoration of blood flow as we moved from the 0.1 mg/kg dose to the 0.6 mg/kg dose. There were no incidences of intra-cerebral haemorrhage (ICH) and no major bleeding events were unequivocally attributed to alfimeprase. The most common adverse event observed was hypotension. All serious adverse events that were observed were reversible, did not result in any clinical sequelae and were compatible with outcomes observed in other thrombolytic trials.
The multi-center, open-label, dose-escalation study evaluating the safety and efficacy of alfimeprase in acute PAO patients was led by Dr. Kenneth Ouriel and Dr. Jacob Cynamon, professor of clinical radiology and director of the division of vascular and interventional radiology at the Montefiore Medical Centre. Patients were randomised to receive one of three doses of alfimeprase, 0.1 mg/kg, 0.3 mg/kg or 0.6 mg/kg. Doses were administered via a side-hole catheter in two separate, five to fifteen minute pulsed infusions, giving 2/3 of the dose up front, followed by the remaining 1/3 of the dose after two hours. Angiograms were taken at baseline (time zero), one hour and two hours with the final and conclusive angiogram taken at four hours after initial dosing.
"Alfimeprase has shown promise in its ability to dissolve blood clots in a rapid time frame, in a dose-dependent fashion and without any major bleeding events attributed to study drug," stated Dr Kenneth Ouriel, chairman of the division of surgery at the Cleveland Clinic and principal investigator for Nuvelo's phase 1 and 2 alfimeprase trials in PAO. "These characteristics show the potential of alfimeprase to be a breakthrough therapy for patients suffering from acute PAO," Dr Kenneth said.
Based on the encouraging preliminary results from this phase 2 trial, Nuvelo plans to meet with the Food and Drug Administration (FDA) to discuss the initiation of a pivotal Phase 3 trial in acute PAO patients to fully assess the safety and efficacy of alfimeprase.
In addition, Nuvelo expects to present the full clinical trial data at a major medical conference this year and to submit a trial manuscript to a peer-reviewed journal for publication.
Alfimeprase is a modified fibrolase that directly degrades fibrin when delivered through a catheter at the site of a blood clot. Compared to traditional plasminogen activators, pre-clinical and clinical studies have shown alfimeprase to be up to six times faster in dissolving clots.
PAO is the blocking of arterial blood flow to a distant part of the body by a clot. PAO usually occurs in the leg and is the result of underlying peripheral arterial disease (PAD), in which chronic fatty plaque build up restricts blood flow.