Carfilzomib Achieves 26 Percent Clinical Benefit Response Rate in Phase 2 Trial of Relapsed and Refractory Multiple Myeloma Patients - Proteolix Expands Trial

ORLANDO, Fla. and SOUTH SAN FRANCISCO, Calif., June 1 /PRNewswire/ -- Proteolix, Inc. today presented results from the company's most advanced clinical trial of single-agent carfilzomib demonstrating anti-cancer activity and progression-free survival in patients with relapsed and refractory multiple myeloma. Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors being developed by Proteolix for the treatment of hematologic malignancies and solid tumors.

Data from the Phase 2 clinical trial of relapsed and refractory multiple myeloma patients were presented today in an oral session by Sundar Jagannath, M.D., Chief of the Multiple Myeloma Program, Bone Marrow and Blood Stem Cell Transplantation at St. Vincent's Comprehensive Cancer Center in New York, at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO). In addition, Proteolix presented positive data today from an ongoing Phase 2 clinical trial of single-agent carfilzomib in relapsed multiple myeloma patients and from a Phase 1b clinical trial of carfilzomib in combination with lenalidomide and dexamethasone during the "Lymphoma and Plasma Cell Disorders" poster session.

"In spite of advances in the treatment of multiple myeloma, new selective agents are needed for patients who have failed other available therapies," said Dr. Jagannath. "Carfilzomib is well tolerated and demonstrates clear single-agent activity in a heavily pre-treated multiple myeloma patient population. Patients enrolled in this Phase 2 trial lack treatment alternatives, having failed prior treatment with all approved agents and stem cell transplant."

Sustained Clinical Benefit in Relapsed and Refractory Patients

The Phase 2 clinical trial enrolled a total of forty-six heavily pre-treated multiple myeloma patients who had failed all other approved agents. Of 39 evaluable patients who received a dose of 20mg/m(2), 18 percent achieved an overall response and 26 percent achieved a clinical benefit response. An additional 41 percent achieved stable disease. Importantly, responses have also been sustained; patients achieving partial or minor responses stayed on therapy for a median treatment duration of 240 days, or approximately 8 months, and the median duration of response was 7.4 months. Ten percent of patients completed twelve cycles of treatment and an extension study has been initiated for patients who have stayed on drug for one year.

All patients enrolled in the Phase 2 trial have relapsed following treatment with bortezomib and an immunomodulatory agent, such as thalidomide or lenalidomide, and were refractory to their last treatment. Eighty percent of patients received at least four prior treatments. Of 26 patients enrolled who were refractory to treatment with bortezomib, 19 percent achieved a clinical benefit response.

Carfilzomib was generally well tolerated and toxicities were manageable. The most common adverse events reported were fatigue, anemia and thrombocytopenia. Of note to this patient population, treatment with carfilzomib was associated with a low incidence of peripheral neuropathy, a common side effect associated with the approved proteasome inhibitor, bortezomib. Exacerbation of pre-existing peripheral neuropathy was rare and did not result in dose reductions or discontinuation of therapy. Overall, adverse events did not limit treatment duration, even among patients with several co-morbidities.

These data were presented by Dr. Jagannath in an oral presentation titled "Final results of PX-171-003-A0, part 1 of an open-label, single-arm, Phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma" (Abstract #8504).

"We are excited by the positive demonstration of patient benefit achieved in our trials of carfilzomib. In particular, the response rates and duration of response among heavily pre-treated patients who lack treatment alternatives are highly encouraging," said Michael Kauffman, M.D., Ph.D., Chief Medical Officer of Proteolix. "Based on the consistent efficacy and safety profile achieved from our preclinical and clinical studies of carfilzomib, we are focused on advancing this promising novel agent through late-stage evaluation, with an eye toward an accelerated approval."

Trial Expanded for Accelerated Approval Strategy

Based on the positive data achieved in this Phase 2 trial, Proteolix has expanded the Phase 2 study to enroll an additional 250 relapsed and refractory multiple myeloma patients. If positive, results from this study could form the basis for a New Drug Application (NDA) filing for accelerated approval with the U.S. Food and Drug Administration in 2010.

Patients initially receive 20mg/m(2) carfilzomib twice a week over a 28-day cycle, followed by doses of 27mg/m(2) for every cycle thereafter for up to twelve cycles. The primary endpoint for the Phase 2 study is overall response rate, defined as a complete response (CR) or partial response (PR). Secondary endpoints include clinical benefit response (CR, PR or minor response (MR)), duration of response, progression-free survival, time to progression, overall survival and safety. To date, more than 140 patients have been enrolled in the study. Proteolix anticipates reporting results from this accelerated approval trial in the first half of 2010.

Carfilzomib Active in Single-Agent and Combination Regimens

Proteolix also presented data from two ongoing studies of carfilzomib in multiple myeloma patients during the Lymphoma and Plasma Cell Disorders poster session.

Interim results from a Phase 2 clinical trial designed to evaluate response rates based on patients' bortezomib treatment history demonstrated substantial response rates, particularly among bortezomib-naive patients. Of 14 evaluable bortezomib-naive patients, 57 percent achieved responses, including one patient with a complete response, two with very good partial responses and five with partial responses. Four additional patients achieved stable disease. Of 31 patients treated, 10 percent have received 12 cycles of treatment and have been enrolled in an extension study. Adverse events were generally mild and manageable. These data were presented by Ravi Vij, M.D., Associate Professor of Medicine, Division of Oncology, Section of Bone Marrow Transplantation at Washington University School of Medicine in a poster titled "PX-171-004, a multicenter Phase II study of carfilzomib in patients with relapsed myeloma: An efficacy update" (Abstract #8537).

Ruben Niesvizky, M.D., Associate Attending Physician, New York-Presbyterian Hospital and Associate Professor of Medicine at Weill Cornell Medical College presented preliminary data from an ongoing Phase 1b dose-escalating trial of carfilzomib in combination with lenalidomide and low-dose dexamethasone in relapsed and refractory patients. The combination of carfilzomib and lenalidomide is well tolerated and encouraging response rates have been observed. Of 18 evaluable patients, 61 percent have achieved partial or minor responses, including three very good partial responses. Notably, responses occurred in the first 28-day cycle of treatment and initial responses have improved with continued therapy. A maximum-tolerated dose has not yet been established and dose-escalation continues. These data were presented today in a poster titled "PX-171-006: Phase Ib multicenter dose escalation study of carfilzomib plus lenalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma: Preliminary results" (Abstract #8541).

About Multiple Myeloma

According to the American Cancer Society, in 2009, approximately 20,500 new cases of multiple myeloma will be diagnosed in the United States. Newly diagnosed patients have treatment options that include combination chemotherapeutic agents and stem cell transplantation. While many patients respond to treatment, most eventually relapse and require subsequent treatment. Few patients are ultimately cured of their disease. In spite of advances in the treatment of multiple myeloma, this year alone, approximately 10,500 patients are expected to die of the disease.

About Carfilzomib

Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors. Carfilzomib produces specific and sustained inhibition of the proteasome, leading to apoptosis in cancer cells with minimal off-target effects. In Phase 1 and Phase 2 clinical trials, carfilzomib has demonstrated single-agent activity in hematologic malignancies and solid tumors, including multiple myeloma, Waldenstrom's macroglobulinemia, mantle cell lymphoma and renal cell carcinoma.

Proteolix is conducting a comprehensive clinical development program evaluating carfilzomib for the treatment of multiple myeloma, including an ongoing accelerated approval study in heavily pre-treated relapsed/refractory patients and a Phase 2 clinical trial in relapsed patients stratified by prior treatment with bortezomib. Both Phase 2 clinical trials are being conducted by Proteolix in collaboration with the Multiple Myeloma Research Consortium (MMRC). A Phase 1b clinical trial of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma is also ongoing. In addition, Proteolix is conducting a single-agent Phase 2 clinical trial of carfilzomib in patients with recurrent or advanced solid tumors. For the latest information regarding ongoing carfilzomib clinical trials, please visit www.clinicaltrials.gov.

About Proteolix

Founded in December 2003, Proteolix, Inc. is a privately-held biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolix's lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor. For additional information on Proteolix, please visit www.proteolix.com.

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