Gensia Pharmaceuticals Inc. announced Monday that itsubmitted on schedule a new drug application (NDA) to FDA onDec. 30 for use of its purine-based drug, Arasine, in patientsundergoing coronary artery bypass graft (CABG) surgery.

The San Diego company also announced that it will file forregulatory approval of Arasine in the European Community inmid-January and for Canadian approval by March.

The NDA for Arasine is based on data from three clinical trials-- one Phase II trial and two Phase III trials -- conducted inmore than 1,500 patients since July 1991. Primary end pointsin the two Phase III studies included fatal and non-fatalmyocardial infarction (MI), adverse myocardial events andsafety.

According to company spokeswoman Elizabeth Gard, Gensia iscurrently finalizing a protocol for use in another double-blind,placebo-controlled, multicenter Arasine trial in approximately1,000 patients.

"Our regulatory and clinical departments believe that we havean approvable package with this NDA," Gard told BioWorld. "Butas an insurance policy, we are conducting an additional study."

The new study will be conducted primarily in the U.S., but in afew European centers as well. Gard said the new study isscheduled to be completed by the end of this year or the firsthalf of 1994.

Arasine is administered to CABG patients during a seven-hourregimen that starts just prior to surgery and continues throughthe patient's recovery period. The synthetically manufactureddrug is believed to promote delivery of oxygen to heart muscletissue through its regulation of the release of adenosine.

Results from the company's Phase II trial, which enrolledapproximately 120 patients undergoing CABG surgery, showeda 64 percent reduction in the incidence of MI in Arasinepatients compared with patients who received a placebo. Thecompany deemed its Phase II results "clinically important," butdue to the small size of the trial, the results were notstatistically significant.

Results from the two Phase III trials -- a U.S. study with 630patients and an international study with 820 patients -- havenot been made public. But according to analyst Rick Stover ofStover Haley Noyes of Stamford, Conn., the U.S. Phase III trialdata shows a statistically significant "magnitude of reduction"for myocardial infarctions similar to that seen in the Phase IItrial.

The company announced last September that a preliminaryanalysis of data from the international study did not showstatistically significant results overall, but that clinically andstatistically significant results were achieved in two subgroupanalyses.

"There were seven to eight countries in the international study,and clinical practices vary from country to country," explainedGard. "This may have explained the lack of overall statisticalsignificance in the international trial."

Full results from both the U.S. and international Phase III trialswill be made public sometime during the next six months in apeer review forum, Gard said.

Stover said that different procedures overseas for the handling,storage and transit of patient samples for an enzyme called CK-MB, which is critical to measuring heart attacks, could accountfor the difference in the U.S. and international trial results.Greg Brown, a thoracic and vascular surgeon who is an analystwith Vector Securities International in Deerfield, Ill., concurred.Brown initiated coverage of the company in December with a"buy" recommendation.

"There was a misinterpretation of the international trial results-- people thought it was an efficacy issue, but it was a studydesign issue," said Brown. "The FDA understands the nuances ofthis enzyme better than Wall Street does."

Brown estimated that Arasine should gain approval aftercompletion of the supplementary 1,000-patient study and thatthe product will be on the market by 1995. Stover said that ifFDA finds sufficient confirmatory data in its analysis of theinternational trial, it may approve Arasine within a 12-monthtime frame, without waiting for the results of the follow-onstudy. But, he said, most analysts have now put the timetablefor approval at 18 months.

Ultimately, Arasine could generate revenues between $500million and $1 billion, according to Stover's estimates. He saidthat the lion's share of Arasine revenues will come from its usein preventing cardiac complications in high-risk patientsundergoing non-cardiac surgeries. The drug is set to beginPhase III trials in the non-cardiac indication sometime in thefirst half of this year.

Gensia's stock (NASDAQ:GNSA) closed Monday at $25.50, up $1per share.

-- Lisa Piercey Business Editor

(c) 1997 American Health Consultants. All rights reserved.