NEW YORK, Nov. 19 Keryx Biopharmaceuticals, Inc.(Nasdaq: KERX) today announced that early results of a phase II single agenttrial of perifosine (KRX-0401) in patients with recurrent malignant gliomaswas presented in a poster presentation on Saturday, November 17, 2007 at the12th Annual Scientific Meeting of the Society for Neuro-Oncology, held inDallas, Texas. The poster, entitled "A Phase II Trial of Perifosine forRecurrent/Progressive Malignant Gliomas, provided an update on the clinicalactivity of single agent perifosine in patients with malignant glioblastoma(GBM) and malignant anaplastic gliomas (AA).
Ph II Study - Interim Results
Twenty-five patients with advanced malignant gliomas were treated with aloading dose of 600 mg (150mg x 4) followed by 100 mg daily dose ofperifosine. Patients must have failed prior radiation therapy and have shownunequivocal evidence for tumor progression by MRI or CT scan. There was nolimitation on the number of prior relapses or prior therapies and patientswith a KPS greater than or equal to 50 were eligible. Patients were notallowed to take enzyme-inducing anti-epileptic drugs (EIAED's). Response wasmeasured by the MacDonald Criteria (PR greater than or equal to 50% decreasein bidirectional tumor area and SD = between 25% worse to 50% better).Patients were broken out into two groups with results as follows:
The median Progression Free Survival (PFS) and Overall Survival (OS) inthe Anaplastic Glioma group was 9 wks (range 2 - 50 wks) and 49 wksrespectively. Toxicity was minimal with the following reported events (n):grade 1 nausea (1), grade 1 diarrhea (1), grade 2 pain (1) and grade 4 goutexacerbation (1). The study was designed to enroll at least 12 evaluable GBMpatients and at least 10 evaluable AA patients. If at least 1 patientachieves 6 month PFS, the study would continue to enroll an additional subsetof patients. Therefore, the GBM arm has been halted and the AA arm willcontinue to enroll. Final study updates will be reported at a future meeting.
I. Craig Henderson, MD, President of Keryx Biopharmaceuticals, commented"We want to further evaluate the role of perifosine in patients with malignantgliomas. The single agent activity observed in patients with anaplasticgliomas is of great interest as these patients are in need of additionaltherapies. We look forward to expanding this patient cohort."
For copies of the poster which was presented during the meeting, pleasecontact Keryx Biopharmaceuticals.
Perifosine (KRX-0401) Mechanism of Action and Profile
Perifosine has been shown to inhibit or otherwise modify signaling througha number of different signal transduction pathways including Akt, MAPK, andJNK. Akt isoforms have been found to be overexpressed in renal, breast,prostate, and pancreatic cancers. Elevated levels of pAkt have beencorrelated with poor prognosis in patients with gastric, hepatocellular,endometrial, prostate, renal cell and head and neck cancers, as well asglioblastoma. The majority of tumors expressing high levels of pAkt werehigh-grade, advanced stage or had other features associated with poorprognosis.
The effects of perifosine on Akt are of particular interest because of 1)the importance of this pathway in the development of most cancers; 2) theevidence that it is often activated in tumors that are resistant to otherforms of anticancer therapy; and 3) and the difficulty encountered thus far inthe discovery of drugs that will inhibit this pathway without causingexcessive toxicity.
To date, over 1,500 patients have been treated with perifosine in trialsconducted both in the US and Europe. Its safety profile is distinctlydifferent from that of most cytotoxic agents. It does not causemyelosuppression (depression of the immune system) or alopecia (hair loss)like many currently available treatments for cancer. In phas