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Acetylon Pharmaceuticals Presented Positive Preliminary Data from Phase 1b/2 Trial of Ricolinostat in Combination with Pomalyst® as Potential Oral Treatment for Patients with Multiple Myeloma

--Data Presented at 20th Congress of the European Hematology Association--


BOSTON – June 15, 2015 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced that the Company presented positive preliminary data from its Phase 1b/2 trial of ricolinostat in combination with Pomalyst® (pomalidomide) and dexamethasone in patients with relapsed-and-refractory multiple myeloma at the 20th Congress of the European Hematology Association, which took place June 11-14, 2015, in Vienna, Austria. Initial data from the evaluation of 28 of the planned 66 patients in the Phase 2 portion of the study reported an overall response rate of 29% at an early median follow-up of 12 weeks, which compares favorably to the historical control of 16.6% at 18.1 weeks with Pomalyst and dexamethasone alone in a similar patient population. Clinical benefit, defined as minimal response or greater, was 50%, and 68% of patients achieved stable disease or better. In the overall study (Phase 1 and Phase 2, n=39), ricolinostat was well-tolerated in combination with Pomalyst. The most common treatment-emergent adverse events were fatigue (41%), diarrhea (38%), and neutropenia (36%), the majority of which were low grade. Grade 3 and 4 adverse events, apart from neutropenia (26%), were uncommon (≤8%). Ricolinostat is an oral selective HDAC6 inhibitor in multiple clinical studies for the potential treatment of multiple myeloma and lymphoma.

“As a physician, it is encouraging to see patients, whose multiple myeloma has progressed while receiving standard-of-care therapy, achieve clinical benefit with the combination of ricolinostat, Pomalyst and dexamethasone. This all-oral combination has been very well-tolerated, making it potentially suitable for treatment of a broad range of patients, including older patients, patients for whom a non-oral drug regimen is limiting, and potentially as a part of an all-oral maintenance regimen,” said Noopur Raje, MD, Director of the Center for Multiple Myeloma at the Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School.

“These early data build on our clinical studies of ricolinostat in combination with Celgene’s oral immunomodulatory drug, Revlimid® (lenalidomide), and indicate that ricolinostat is an active oral agent and well-tolerated in the relapsed-and-refractory multiple myeloma patient population in combination with Celgene’s third-generation IMiD® drug, Pomalyst,” commented Catherine A. Wheeler, MD, Senior Vice President Clinical Development and Chief Medical Officer of Acetylon.

The Phase 1b/2 clinical trial is a multi-center, open-label study designed to assess the safety, tolerability and efficacy of ricolinostat in combination with Pomalyst and low-dose dexamethasone. The primary endpoint is overall response rate. The Phase 1b portion was a 3+3 design in which ricolinostat (160 mg) was given QD (once daily) or BID (twice daily) combined with Pomalyst (4 mg) for 21 days of a 28-day cycle with dexamethasone (40 mg) on days 1, 8, 15 and 22. 7 patients were treated in the Phase 1b portion, with 3 at 160 mg QD and 4 at 160 mg BID. In the ongoing Phase 2 portion, up to 66 patients will be enrolled – of those patients, 32 had been enrolled as of April 27, 2015, of which 28 were evaluable for response. Ricolinostat is being administered orally as 160mg QD for 21 days of a 28-day cycle.

Major highlights from the presentation include:

  • The optimal dose and schedule for ricolinostat in combination with Pomalyst and dexamethasone was determined to be 160mg QD on days 1-21 of a 28-day cycle. Patients at this dose experienced no dose-limiting toxicities. At 160mg BID, some clinically-relevant grade 2 diarrhea was observed.
  • Co-administration of Pomalyst and ricolinostat did not alter either agent’s pharmacokinetic profile.
  • 57% (16) of the Phase 2 evaluable patients remained on study after a median of 3 months on therapy, while 43% of patients discontinued treatment for reasons of progressive disease (6), a non-fatal adverse event (3), patient decision (2) and investigator decision (1).
  • The combination of ricolinostat, Pomalyst and dexamethasone was generally well-tolerated. Serious adverse events considered possibly related to ricolinostat were bronchitis, chronic cardiac failure, pneumonia and renal failure, each reported for 1 patient. A single grade 4 adverse event, neutropenia, was reported to be possibly related to ricolinostat. Grade 3 related adverse events reported in 2 or more patients included diarrhea (3) and neutropenia (4).

About HDAC6 Inhibition

Blood cancers such as multiple myeloma and lymphoma are characterized by successive genetic mutations resulting in uncontrolled cell proliferation and dysfunctional production of intracellular proteins. Ricolinostat (ACY-1215) and ACY-241 selectively inhibit the intracellular enzyme HDAC6, which leads to an accumulation of excess protein and in addition may disrupt critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers programmed cell death, called "apoptosis," with little or no effect on normal cells. Currently available HDAC drugs also affect the expression of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage and profound fatigue as well as potential for significant cardiac toxicity. 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

Acetylon Pharmaceuticals, Inc., based in Boston, Massachusetts, is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhancement of therapeutic outcomes in cancer and other critical human diseases. The Company’s epigenetic drug discovery platform has yielded a proprietary portfolio of optimized, orally-administered Class I and Class II histone deacetylase (HDAC) selective compounds. Alteration of HDAC regulation through selective HDAC inhibition is thought to be applicable to a broad range of diseases including cancer, sickle cell disease and beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon’s lead drug candidate, ricolinostat (ACY-1215), is a selective HDAC6 inhibitor currently in Phase 2 clinical development for the treatment of multiple myeloma. The Company recently announced a strategic collaboration agreement with Celgene Corporation, which includes an exclusive option for the future acquisition of Acetylon by Celgene. Acetylon’s scientific founders are affiliated with Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com


IMiD®, Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation.



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