Rocilinostat Combination Study with Millennium Takeda's Velcade® (Bortezomib) and Dexamethasone Advances into Phase 1b
BOSTON, Mass. – August 1, 2012 -- Acetylon Pharmaceuticals today announced it has initiated patient enrollment in a new Phase 1b clinical trial of its lead drug candidate rocilinostat (ACY-1215) in combination with Revlimid® (lenalidomide) and dexamethasone for the treatment of relapsed and relapsed/refractory multiple myeloma. Rocilinostat is an oral Class II histone deacetylase (HDAC) inhibitor selective for the intracellular enzyme HDAC6. Acetylon believes that selective HDAC6 inhibition may provide enhanced anti-cancer effectiveness through potentially improved tolerability compared to current non-selective inhibitors, which inhibit both Class I and Class II HDACs. Celgene is providing free access to its disease-altering therapy, Revlimid®, for patients participating the clinical trial.
"Celgene's recent investment in Acetylon has allowed us to expand our clinical development program to evaluate the safety and potential anti-tumor activity of rocilinostat (ACY-1215) in a new Phase 1b trial in an all-oral combination regimen with Revlimid®, plus dexamethasone," said Walter C. Ogier, President and Chief Executive Officer and co-founder of Acetylon. "Though the mechanism of action is not fully known, Revlimid® is a foundation treatment for patients with multiple myeloma through its unique immunomodulatory, antiangiogenic and antineoplastic properties. This new clinical trial will enable us to study whether selective HDAC6 inhibition, which triggers apoptosis in malignant cells, may have a synergistic effect when combined with Revlimid® and dexamethasone to treat patients who are relapsed and relapsed/refractory with multiple myeloma."
In addition, the Company announced that it has begun patient enrollment of a Phase 1b trial of rocilinostat in combination with the first-in-class proteasome inhibitor, Velcade® (bortezomib) and dexamethasone, also for the treatment of relapsed and relapsed/refractory multiple myeloma. The Phase 1a portion of the clinical trial began in September 2011 and is ongoing. The trial is being conducted by Acetylon with alliance support from The Leukemia & Lymphoma Society (LLS).
Catherine A. Wheeler, MD, Vice President of Clinical Development of Acetylon commented, "Rocilinostat has been well tolerated by patients in our ongoing Phase 1a monotherapy trial, which has allowed us to accelerate initiation of the Phase 1b portion of the trial, combining rocilinostat treatment with Velcade® plus dexamethasone."
About the Phase 1b Trial of ACY-1215 in Combination with Revlimid® (Lenalidomide) and Dexamethasone
The Phase 1b trial is an open-label, multicenter, dose-escalation study to evaluate the safety and efficacy of rocilinostat (ACY-1215) in combination with Revlimid® (lenalidomide) and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. The primary outcome of the study is to establish the optimal dose of rocilinostat over a 28-day treatment cycle. Rocilinostat will initially be administered orally on days 1-5 and 8-12 of the 28-day dosing schedule. Additional regimens may be evaluated based on the outcome of the first schedule. Enrollment has been initiated at The Fred Hutchinson Cancer Research Center of the University of Washington (Seattle, WA) and at the Sarah Cannon Research Institute (Nashville, TN) and additional centers are planned.
About the Phase 1b Trial of ACY-1215 in Combination with Velcade® (Bortezomib) and Dexamethasone
The Phase 1b portion of the previously announced Phase 1/2 clinical trial is enrolling patients with relapsed or relapsed/refractory multiple myeloma in a 21-day treatment cycle to determine the maximum tolerated dose of rocilinostat (ACY-1215) in combination with Velcade® (bortezomib) and dexamethasone, followed by up to five additional sequential cycles of treatment. The Phase 1a portion of the trial continues to enroll the same group of patients in a 21-day treatment cycle to determine the maximum tolerated dose of rocilinostat as monotherapy, followed by up to five additional sequential cycles of treatment. The trial is being conducted in major cancer centers in the United States, including the Massachusetts General Hospital Cancer Center, the Medical College of Wisconsin, the Emory University Winship Cancer Institute, the University of Pennsylvania Abramson Cancer Center, the Mount Sinai Medical Center Tisch Cancer Institute (New York, NY) and one other hospital still pending initiation.
Blood cancers such as multiple myeloma are characterized by successive genetic mutations resulting in rapid cell proliferation and excess production of intracellular proteins. ACY-1215 selectively inhibits the intracellular enzyme HDAC6, leading to inactivation of the "aggresome" pathway for degradation of damaged proteins. The resultant accumulation of excess waste protein in malignant cells triggers programmed cell death, called "apoptosis," with little or no effect on normal cells. Currently available HDAC drugs non-selectively target multiple HDAC enzymes including those of Class I, resulting in dysregulated expression of numerous genes in normal cells as well as cancer cells. Side effects commonly associated with non-selective HDAC drugs include gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage, and profound fatigue as well as potential for severe cardiac complications. Selective inhibition of HDAC6 is expected to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and may enable the development of optimized treatment regimens including maximally effective combination drug therapies.
About Acetylon Pharmaceuticals, Inc.
Acetylon Pharmaceuticals, Inc. is applying its unique capabilities to discover and develop next-generation, highly selective small molecule drugs to realize the therapeutic potential of HDAC inhibition to treat cancer, inflammatory and other diseases, while reducing the side effects common to this class of drugs. The Company is located in Boston and is based on technology initially developed at the Dana-Farber Cancer Institute and at Harvard University. www.acetylon.com
Revlimid® is a registered trademark of Celgene Corporation. Velcade® is a registered trademark of Millennium: the Takeda Oncology Company.
Walter C. Ogier
President and Chief Executive Officer
MacDougall Biomedical Communications