Acetylon Pharmaceuticals Presents Encouraging Safety and Clinical Response Data from Ongoing Clinical Trials of ACY-1215

Acetylon Pharmaceuticals Presents Encouraging Safety and Clinical Response Data from Ongoing Clinical Trials of ACY-1215 for the Treatment of Multiple Myeloma

-- Data Presented at the 18th Congress of the European Hematology Association --

BOSTON – June 17, 2013 – Acetylon Pharmaceuticals Inc., the leader in development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced the presentation of clinical data of the Company’s lead candidate, ACY-1215, for the treatment of relapsed or refractory multiple myeloma at the 18th Congress of the European Hematology Association (EHA), on June 15th, 2013, in Stockholm, Sweden. ACY-1215 is an oral, selective HDAC6 inhibitor currently being evaluated in a Phase 1b clinical trial in combination with the best-in-class drug Revlimid® (lenalidomide, Celgene) and a Phase 1/2 clinical trial in combination with the first-in-class drug Velcade® (bortezomib, Takeda Millennium) for the treatment of relapsed or refractory multiple myeloma.

“ACY-1215 is very well tolerated, both as a single agent and in combination with either Revlimid or Velcade at biologically relevant exposures in patients with relapsed or refractory multiple myeloma,” said Catherine A. Wheeler, MD, Vice President, Clinical Development of Acetylon. "We are encouraged by the number of early clinical responses that have been observed in combination therapy. In the Phase 1b study in combination with Revlimid, eight out of ten evaluable patients to date achieved disease response, including one complete response (with marrow confirmation), two very good partial and four partial responses observed. No dose limiting toxicities or severe adverse events, which are common with previous generation non-selective HDAC inhibitors, have been observed in this trial, and dose escalation is continuing. Activity has also been observed in heavily pretreated patients in combination with Velcade in the ongoing Phase 1/2 study, including three partial responses and one minor response to date in thirteen evaluable patients. Responses in both trials have been durable, with patients remaining on study for up to 11 months.”

Preliminary ACY-100 Phase 1/2 Data

ACY-100 is a single arm multicenter open label Phase 1/2 study with dose escalation of ACY-1215 as a monotherapy and in combination with Velcade® (bortezomib, Takeda Millennium) and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma. At the time of data cut-off, 28 patients were enrolled in Phases 1a and 1b. Patients received single agent ACY-1215 in doses of 40 mg to 360 mg orally on days 1-5 and 8-12 of a 21 day cycle in Phase 1a, and with Velcade administered days 1, 4, 8 and 11 as well as 20 mg of dexamethasone the day of and the day after Velcade dosing in Phase 1b. With ACY-1215 monotherapy, no dose-limiting toxicities were observed and creatinine elevations, anemia, fatigue, hypercalcemia and respiratory infection, the most common toxicities, were mostly low grade and not attributed to ACY-1215. Possibly related grade 3 toxicities were anemia and low white blood cell counts. Treatment resulted in six of fifteen heavily pretreated patients achieving stable disease. With ACY-1215, Velcade and dexamethasone combination therapy, treatment was well-tolerated up to 160 mg daily dosing of ACY-1215 (with dose escalation ongoing) with no dose-related adverse events and few grade 3 and 4 related adverse events. Three partial responses, one minor response and four stable disease outcomes were observed out of thirteen heavily pretreated patients evaluable for response assessment (at up to 80 mg daily dosing).

Preliminary ACE-MM-101 Phase 1b Data

The Phase 1b trial is an open-label, multicenter, dose-escalation study to evaluate the safety and efficacy of ACY-1215 in combination with Revlimid® (lenalidomide, Celgene) and dexamethasone in patients with relapsed or refractory multiple myeloma. Patients receive Revlimid, 25 mg after an initial safety cohort at 15 mg, daily on 21 days of a 28 day schedule and 40 mg dexamethasone weekly. In schedule A, ACY- 1215 is being dosed days 1-5 and 8-12 and dose levels of 40 to 240 mg are being explored. If that schedule is well tolerated, a third week of ACY-1215 (schedule B) day 15-19 will be examined. Preliminary results demonstrate that ACY-1215 is well-tolerated in combination with Revlimid and dexamethasone at up to 160 mg daily dosing, and dose escalation is ongoing. No dose-limiting toxicities or serious adverse events have been observed to date. One grade 3 adverse event (neutropenia) was possibly related to ACY-1215, and other adverse events were low grade with no dose relationship observed. Responses have been observed in eight of ten patients evaluable for response, including one complete response, two very good responses, four partial responses and one minor response.

About ACY-1215

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. ACY-1215 selectively inhibits 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 affect the expression of numerous 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 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

Acetylon Pharmaceuticals, Inc. is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhanced therapeutic outcome of cancer and other critical unmet medical needs. The Company’s epigenetic drug discovery platform has initially yielded a proprietary library 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, beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon’s lead drug candidate, ACY-1215, is a selective HDAC6 inhibitor in clinical development for the treatment of multiple myeloma.   www.acetylon.com

CONTACT:

Walter C. Ogier

President and Chief Executive Officer

(617) 245-1300

wogier@acetylon.com

MEDIA:

MacDougall Biomedical Communications

(781) 235-3060

Kari Watson, kwatson@macbiocom.com or

Michelle Avery, mavery@macbiocom.com
 

Posted: June 2013

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