Ambit Announces Presentations At The 55th Annual Meeting Of The American Society Of Hematology (ASH)

SAN DIEGO, Dec. 9, 2013 /PRNewswire/ -- Ambit Biosciences (Nasdaq: AMBI), a biopharmaceutical company focused on discovery and development of drugs targeting unmet needs in oncology, autoimmune and inflammatory disease, today announced four oral presentations given at the 55^th Annual ASH Conference in New Orleans, with data highlighting the Company's lead drug candidate, quizartinib. 

Results of the Phase 2b Randomized, Open-Label, Study of Lower Doses of Quizartinib in Subjects with FLT3-ITD Positive Relapsed Acute Myeloid Leukemia (AML): The purpose of this study is to assess the efficacy and safety of lower doses of quizartinib in the treatment of patients 18-years or older with relapsed/refractory FLT3 ITD positive AML to further improve the benefit:risk assessment of quizartinib.

This preliminary analysis is based on data available through May 28, 2013 with a minimum of eight weeks of follow up since the last subject first visit.  A total of 76 patients were enrolled from May 21, 2012 to March 27, 2013.  Median age for all patients was 55 (19-77) and 92% were FLT3-ITD(+).  35 patients remained in follow-up at the time of the analysis, and are currently censored for overall survival.  The following key information was presented:

For dose of 30mg:

• The CRc rate was 47 percent (5 percent CR+CRp, 42 percent CRi)
• The rate of HSCT after quizartinib use was 32 percent
• The median overall survival was 20.7 weeks, with 16/38 patients censored as they remained in follow-up at the time of the analysis
• Of the 12 patients who were bridged to HSCT, the median overall survival was 31 weeks
• Grade 2 or greater QT prolongation was 11%, with a 5% grade 3 rate and no grade 4 events

For dose of 60mg:

• The CRc rate was 47 percent (5 percent CR+CRp, 42 percent CRi)
• The rate of HSCT after quizartinib use was 42 percent
• The median overall survival was 25.4 weeks, with 19/38 patients censored as they remained in follow-up at the time of the analysis
• Of the 16 patients who were bridged to HSCT, the median overall survival is 28.1 weeks
• Grade 2 or greater QT prolongation was 17%, with a 3% grade 3 rate and no grade 4 events

Overall conclusions:  Both the 30mg and the 60mg doses showed substantial activity in terms of overall CRc rate and bridge to HSCT with impact on improved median OS.  The safety profile is similar at both doses yet QTcF prolongation appears dose dependent, with decreased QTcF prolongation at both the 30 and 60mg doses compared to the prior Phase 2 study findings which utilized higher doses of quizartinib. 

Next steps include a global phase 3 randomized study of quizartinib in FLT3-ITD(+) patients in 1st relapse planned to start in early 2014 pending final FDA feedback on our recommended starting dose.

Quizartinib Can Be Safely Combined With Conventional Chemotherapy In Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Experience From The AML Pilot Trial: This is the first presentation of quizartinib use in combination with chemotherapy in newly diagnosed older AML patients, testing the feasibility and dose which could be given sequentially following conventional chemotherapy in patients over the age of 60 years. The following key information was presented:

A total of 55 patients were recruited in the United Kingdom between September 1, 2011 and April 29, 2013.  Patients were age 60 or above with a median age of 69 years (ranging from 62-75).  All patients were newly diagnosed with AML with 48 evaluable patients exposed to quizartinib. Complete follow-up was to the end of July 2013.  Study endpoints included response and toxicity assessments.  Four dose levels (60mg x 7 days; 60mg x 14 days; 40mg x 7 days; 40mg x 14 days) of quizartinib with conventional chemotherapy were studied.

Overall study results showed in the 48 evaluable patients:

• 31/48 (65%) CR rate
• In the seven patients with either a FLT3 ITD mutation or a tyrosine kinase domain (TKD) mutation who were evaluated for response, 7/7 (100%) achieved a CR
• The most common dose limiting toxicity was grade 3 QT prolongation in three patients
• Median survival was 484 days (16 months)
• 30/48 evaluable patients still alive at last follow-up

Conclusions:

• Combining quizartinib with standard chemotherapy is feasible in older patients at a dose of 40mg for 14 days with multiple rounds of chemotherapy
• Prolongation of QTc (6%) was the most frequent DLT
• The CR rate was at least comparable to the expected rate with chemotherapy alone with no added impairment or neutrophil/platelet regeneration with the addition of quizartinib

Next step is to incorporate quizartinib into the MCRI AML-18 trial with a maintenance component to assess efficacy of quizartinib in elderly newly diagnosed AML patients.

Results of Phase 1 Study of Quizartinib In Combination with Induction and Consolidation Chemotherapy in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia: This dose escalation study is the first to report data on quizartinib in combination with standard induction and consolidation chemotherapy in patients between the ages of 18 to 60-years with newly diagnosed AML, regardless of FLT3 status. The following key information was presented:

A total of 18 patients were recruited in the US for this dose escalation study with a modified 3+3 design to determine the MTD and dose for future studies. 

Quizartinib dose levels tested, starting on day 4 of chemotherapy:

• Dose Level 1 (DL1)   = 60 mg for 7 days
• Dose Level 2 (DL2)   = 60 mg for 14 days
• Dose Level -1 (DL-1) = 40 mg for 14 days

Median age for dose level 1 was 49 years (ranging from 23-59 years) with three FLT3-ITD (+) patients; median age for dose level 2 was 43 years (ranging from 24-58 years) with three FLT3-ITD (+) patients; median age for dose level -1 was 36 years (ranging from 22-60 years) with two FLT3-ITD (+) patients.

Overall, of the 18 patients treated, 15 (83%) achieved a CRc with a 61% CR rate.   Of the 8 FLT3 ITD (+) patients, 7 (88%) achieved a CRc with 6 (75%) achieving a CR.  A total of 8/18 (44%) patients went to a HSCT after therapy.  There were a total of 4 DLTs (all grade 3) which included hyponatremia, pericardial effusion, QT prolongation and pericarditis.

Conclusions:

• The data from this Phase 1 study demonstrated that quizartinib was well tolerated with induction and/or consolidation chemotherapy in newly diagnosed younger adults with AML
• MTD was 40 mg for 14 days or 60 mg for 7 days

Based on these findings, follow-on studies in newly diagnosed AML patients are planned.

A Phase I Study of Quizartinib in Combination with Cytarabine and Etoposide in Relapsed/Refractory Childhood ALL and AML: A Therapeutic Advances in Childhood Leukemia & Lymphoma Study: This was the first clinical trial using quizartinib in children between the ages of 1 month and 21-years with relapsed/refractory AML or MLL-rearranged ALL. The following key information was presented:

A total of 22 patients were enrolled with 18 patients having relapsed AML, eight of which were FLT3 ITD positive.  Multiple doses/m2 were studied. 

The 2 DLTs were grade 3 elevated lipase and grade 4 bilirubin increases.

Of the 18 patients evaluable for response, four achieved a CRc with 3/6 (50%) of the FLT3 ITD positive relapsed AML patients achieving a CRc.  Two relapsed AML patients were taken to HSCT after achieving a CR to therapy.

Conclusions:

Quizartinib was well tolerated at 60mg/m2 in combination with chemotherapy in pediatric patients with relapsed ALL or AML.  Responses were encouraging especially in those with FLT3 ITD positive relapsed AML, and further studies in pediatric patients are warranted.

The four ASH presentations can be accessed on the Ambit Biosciences website at www.ambitbio.com and the abstracts can be accessed on the ASH website at http://hematology.org.

About Ambit Biosciences
Ambit is a biopharmaceutical company focused on the discovery, development and commercialization of drugs to treat unmet medical needs in oncology, autoimmune and inflammatory diseases by inhibiting kinases that are important drivers for those diseases. Ambit's lead drug candidate, quizartinib (AC220), is a once-daily, orally-administered potent and selective, inhibitor of FMS-like tyrosine kinase-3 (FLT3) and is currently under clinical development in patients with relapsed/refractory AML and in newly diagnosed AML patients in combination with chemotherapy as well as maintenance following a hematopoietic stem cell transplantation (HSCT). In addition to quizartinib, Ambit's clinical pipeline includes AC410, an oral JAK2 inhibitor, and CEP-32496, a BRAF inhibitor licensed to Teva Pharmaceutical Industries Ltd. Ambit's preclinical portfolio includes a proprietary CSF1R inhibitor program.

Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with Ambit's expectations regarding the presentation of data from clinical trials and the clinical benefits to be derived from quizartinib, the future development and therapeutic potential of quizartinib, , the progress and expected timing of clinical trials and plans regarding future clinical trials of quizartinib,. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as  "plans," "expects," "anticipates," "hopes", "may," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Ambit's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. These and other risks concerning Ambit's programs are described in additional detail in Ambit's SEC filings. All forward-looking statements contained in this press release speak only as of the date on which they were made. Ambit undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

SOURCE Ambit Biosciences