PeriCor Therapeutics Inc., which resurrected a cardioprotective agent that appeared to have died more than 10 years ago, licensed the Phase III product to Schering-Plough Corp.
Schering-Plough gained worldwide rights to the first-in-class product acadesine for use in preventing complications of cardiac surgeries. The adenosine-regulating agent is in Phase III development for preventing ischemia-reperfusion injury, a complication of cardiac surgery in patients undergoing coronary artery bypass graft surgery using cardiopulmonary bypass.
Trial data disclosed last year showed acadesine, delivered by intravenous infusion, demonstrated a statistically significant 77 percent reduction in mortality among CABG surgery patients who suffered post-reperfusion myocardial infarction. Among those patients, 6.5 percent of patients in the drug group (3/46) died vs. 27.8 percent in the placebo group (15/54; p=0.006).
Specific terms of the deal were not disclosed, but include a license fee and potential milestone and royalty payments to New York-based PeriCor, said Richard Stover, president and CEO.
The acadesine technology has been in development for many years, including previously under the names Arasine and Protara by the former Gensia Inc. The FDA rejected a new drug application for the agent in 1994, another Phase III trial failed to demonstrate efficacy and Gensia later settled a resulting class-action lawsuit.
Gensia in 1996 reorganized as a new company, and spun out certain programs, including the adenosine regulating agents, to Metabasis Therapeutics Inc. Stover said the technology was out of the area of focus for Metabasis, which in 2000 granted rights to Dennis Mangano - a lead investigator on earlier studies - who initiated new development efforts.
Mangano and Stover founded PeriCor in 2004 around the program. The privately held company has kept a low profile since then, other than the data presented last year.
"What we like most about this deal," Stover told BioWorld Today, "is that we're putting it into the hands of very capable people in the cardiovascular area in terms of implementing Phase III trials and commercialization. It is our belief that in the past it was the clinical trials that failed the drug. Schering agreed with us. We don't want that to happen again.
"The history of specialty pharma itself is there have been early disappointments and as things progress the value of a medicine is recognized due to where the science is later rather than where it was originally," Stover said, citing calcium channel blockers as an example.
"As things evolve, I think you will find this whole area to be quite fascinating in terms of the need for cardioprotection," he said. "CABG surgery is one of the most obvious places, but virtually every heart attack patient who gets treated should be treated with something that gives the heart protection from reperfusion injury."
Acadesine has been studied in five placebo-controlled trials of patients undergoing CABG surgery. A meta-analysis of the 4,043 patients enrolled in those studies demonstrated a 26 percent reduction in the incidence of adverse perioperative cardiovascular events, including heart attack, stroke and cardiac death, the companies said.
Schering-Plough, of Kenilworth, N.J., said an additional Phase III trial is planned, to evaluate acadesine in high-risk patients, defined either as females, or males with a history of CABG surgeries or cardiovascular events.
Specifics on the study were not disclosed. Company officials, however, said that trial would be expected to be the final one needed to support registration.
Metabasis, of San Diego, retained a royalty interest in acadesine, and also has an undisclosed equity stake in PeriCor. Stover said PeriCor has received all its funding from private sources, such as high-net-worth individuals. It has received no venture funding.
While acadesine is its lead adenosine regulating agent, PeriCor has three analogues that have been tested in early trials in humans. Those compounds are not part of the deal with Schering-Plough, although the pharmaceutical company does have rights of first refusal on them, Stover said.
PeriCor said adenosine regulating agents, or ARAs, amplify the body's own protective response to ischemia and reperfusion injury, the tissue damage that occurs even after interrupted blood flow is restored. The cardioprotective agents show promise of becoming the first class of "preconditioning mimetic" agents, it said, adding that ARAs work in a highly site- and event-specific manner, enhancing localized release of adenosine exclusively in ischemic tissue while avoiding the systemic complications of adenosine.
PeriCor previously said the protection provided by ARAs is not limited to heart tissue during CABG, with the technology having potential protective benefits in other organs and conditions. It now intends to evaluate the analogues further.
"With the data we have in CABG with acadesine, we don't believe there is a better compound that can be developed for it," Stover said. "The analogues might be better suited in other indications that require longer durations of treatment. We look at our analogues as the opportunity to exploit an expanded range of applications."
For Schering-Plough, the drug means "a strengthening, building and broadening of our cardiovascular franchise, and also a demonstration of Schering-Plough's ongoing commitment to cardiac care," said Lee Davies, director of global communications for the Kenilworth, N.J-based pharmaceutical firm.
Schering-Plough's cardiovascular portfolio also include the approved GP IIb-IIIa inhibitor Integrilin and, with Merck & Co. Inc., the cholesterol-lowering drugs Vytorin and Zetia. It also has in late-stage development the thrombin receptor antagonist SCH-530348.