Alkermes Inc. reported that the combination of drug delivery agentRMP-7 and chemotherapeutic agent carboplatin deliveredintravenously to patients with recurrent, malignant brain tumors,tested in the company's two European Phase II clinical trials, waswell tolerated and provided positive responses as measured bypatients' neurological impairment, performance status and tumorvolume.
Both studies treated patients with recurrent, malignant brain tumors,Richard Pops, CEO of Alkermes, told BioWorld Today. However,Study-013 enrolled patients who had relapsed following previoustreatment with surgery and radiotherapy; Study-019 enrolled furtheradvanced patients who had relapsed following previous treatmentwith surgery, radiotherapy and chemotherapy.
Cambridge, Mass.-based Alkermes, which develops products basedon drug delivery systems, focuses on two drug delivery opportunities:controlled, sustained release of injectable drugs lasting several daysto several weeks, using its ProLease and Medisorb technologies; andthe delivery of drugs into the brain past the blood-brain barrier, usingRMP-7 technology.
"Malignant brain tumors kill you," Pops said, "and there has not beena new chemotherapeutic agent since the 1960s. The problem is thatdespite the fact that new chemotherapeutic agents are beingdeveloped, most of them do not cross the blood-brain barrier."
RMP-7 opens up the blood brain barrier for a brief period of time,"Pops said.
RMP-7 is an analogue of a natural molecule called Bradykinin, Popsexplained. "Bradykinin is a natural mediator of vascular permeability.We harness Bradykinin's ability to change the permeability of bloodvessels," he said.
Study-013 enrolled 45 patients at nine centers in the U.K. Treatmentwith RMP-7 and carboplatin resulted in positive responses in 61percent to 87 percent of patients as measured by tests of theirneurological impairment and performance status, and positiveresponses in approximately 75 percent of patients as measured by thesize of their tumor on MRI.
Study-019 enrolled 42 further advanced patients at 11 centers in theU.K., Sweden and France. Treatment with RMP-7 and carboplatinresulted in positive responses in 40 percent to 57 percent of patientsas measured by neurological impairment and performance status, andpositive responses in approximately 25 percent of patients asmeasured by tumor size on MRI.
In both studies, patients received treatment cycles of RMP-7 andcarboplatin once approximately every four weeks. Each cycleconsisted of a 15-minute intravenous infusion of carboplatin andconcurrent 10-minute intravenous infusion of RMP-7 (300 ng/kg).
The endpoints of the studies included response rates over the firstfour cycles of treatment as determined by stabilization orimprovement for a minimum of two cycles of treatment as measuredby three standardized tests of neurological impairment and patientperformance status; and stabilization or reduction in tumor volume byat least 50 percent for a minimum of two cycles as measured bycontrast-enhanced MRI and survival.
Treatment with the combination continued until a patient's clinicalstatus deteriorated or there was evidence of tumor progression by theEFIT or MRI.
Pops said Alkermes is waiting for results from a double-blind,placebo-controlled U.S. study, to be completed in April, comparingtreatments of Rmp-7 with carboplatin to treatment with carboplatinalone.
At the completion of these studies, Pops said, Alkermes hopes to filefor FDA approval.
Alkermes' stock (NASDAQ:ALKS) increased $2.313 Wednesday toclose at $19.75 per share. n
-- Frances Bishopp
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