New Medicines

QinprezoAcute myeloid leukaemia (AML), relapsed or refractory


New molecular entity
Denovo Biopharma
Denovo Biopharma

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Jan 21Vosaroxin is shown as being in PII development on Denovo ´s pipeline; no plans for filings apparent [26].
Dec 19Denovo Biopharma LLC has announced it has licensed Vosaroxin from Sunesis Pharmaceuticals [25].
Jan 19Sunesis 2018 potential pipeline milestones included exploring strategic alternatives to continue development and commercialization for vosaroxin. They continue to support limited investigator-sponsored trials with vosaroxin. Failure to find a partner to license and complete development of vosaroxin will result in the complete discontinuation of vosaroxin development and returning rights to their licensor, Sumitomo Dainippon [22,23].
Jan 19Vosaroxin is still listed in Sunesis pipeline [21].
p>May 17: Sunesis has not said it will give up on the program just yet, but will not be investing in an expensive clinical trial for now. Instead, it hopes to rely on a modest investment in investigator-led studies to try to build data for vosaroxin while it turns its attention to other projects [20].

May 17: The company announces that as a result of further discussions with the EMA CHMP, they have withdrawn the Marketing Authorisation Application for vosaroxin and will reduce investment in their AML programme. The decision came after the CHMP indicated that a positive opinion was unlikely based on the clinical trial results presented [19].

Dec 15: Sunesis announce that vosaroxin has been filed in the EU for treatment of AML [17].

Jul 15: FDA call for more clinical evidence before a MA is filed for vosaroxin, which failed a late-stage trial in October as it did not significantly improve overall survival vs. placebo [15].

Nov 14: Sunesis submits a letter of intent to file a MAA with the EMA seeking approval of vosaroxin, in combination with cytarabine for the treatment of relapsed or refractory AML. The company intends to submit the MAA in H2 2015. The company also expects to meet the US FDA for deciding an appropriate regulatory route for approval in the US [14].

Nov 14: Sunesis initiated the MAA procedure for vosaroxin, for treatment of patients with relapsed or refractory AML, in the EU. The company also expects to meet the US FDA for deciding an appropriate regulatory route for approval in the US [13].

May 12: Granted orphan drug designation for treatment of AML in the EU [6].

Feb 11: Granted Fast Track designation by the FDA for the treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin was granted orphan drug designation by the FDA in 2009 [3].

Dec 10: PIII VALOR trial started [2]

Jun 10: PIII study in AML planned to start in 2H 2010 [1].


First-in-class anticancer quinolone derivative (AQD)
AML is an uncommon disease and affects about 2,000 adults and about 50 children in the UK each year. Most cases occur in people aged over 50. AML is rare in people under the age of 20. It is slightly more common in men than in women [5].
Acute myeloid leukaemia (AML), relapsed or refractory

Further information


Trial or other data

Jan 21PII (NCT03338348) trial completed in Oct 19 after enrolling only 9 patients. As at Jan 20, PII/III AML18 (NCT02272478) trial was still recruiting, and aiming for 1,600 participants. It is now due to complete collection of primary outcome data in Feb 21. As at Oct 20, PII/III BIG-1 study (NCT02416388) trial was also recruiting, aiming for 3,100 participants, and still aiming to complete collection of primary outcome data by Jun 24 [27].
Jul 18Three university-sponsored studies are currently recruiting: PII (NCT03338348) is comparing vosaroxin with azacitidine in 168 older patients with newly diagnosed AML and intermediate or adverse genetic risk or MDS-EB-2 (due to complete collection of primary outcome data in Dec 21). PII/III AML18 (NCT02272478), with collaboration from Cancer Research UK, is evaluating several relevant therapeutic questions in AML and high risk myelodysplastic syndrome. The trial is primarily designed for patients over 60 years considered fit for an intensive chemotherapeutic approach. Vosaroxin is being assessed in combination with decitabine. Collection of primary outcome data is due to complete Oct 19. PII/III BIG-1 study (NCT02416388) is an open label study with multiple randomization phases at differents stages of AML treatment (induction, consolidation and HSCT where applicable) is designed to improve OS in younger (18 to 60 year-old) patients, with AML risk-adapted patient strategies. Within the intermediate risk AML group, optimal GvHD prophylaxis following allogeneic SCT in first CR, after either myeloablative (MAC) or reduced intensity (RIC) conditioning, will also be evaluated. With an adaptative design, this clinical trial could test up to 3 novel AML agents of interest, including vosaroxin. Collection of primary outcome data is due to complete Jun 24 [24].
Jul 15Results of VALOR (NCT01191801) PIII, double-blind, placebo-controlled trial published in the Lancet Oncology. RCT (n=n=711) found addition of vosaroxin to cytarabine therapy did not lead to improvement in overall survival (7.5 months vosaroxin vs. 6.1 months cytarabine group; p=0.061). More patients achieved complete remission in vosaroxin group [16].
Nov 14VALOR reported at ASH. In patients with relapsed or refractory AML, the addition of vosaroxin to cytarabine improved overall survival (median of 7.5 months vs. 6.1 months with cytarabine alone; p=0.02 when accounting for the stratification factors) [12].
Oct 14VALOR study results (n=711): vosaroxin failed to reach the study’s primary endpoint of a statistically significant improvement in overall survival for patients with AML. Secondary endpoint of a clinically significant benefit in the complete remission (CR) rate of AML in patients was reached. Despite this, a marketing authorisation application will be filed with the EMA. [11]
Apr 14PIII VALOR trial estimated completion date: June 2014. [10]
Jun 13Independent Data and Safety Monitoring Board has completed its latest periodic safety review and recommended that the trial continue as planned without changes to study conduct [9].
Mar 13As of 12 March 2013, 563 patients enrolled into the VALOR trial. Planned interim safety analysis by the DSMB expected June 2013, completion of patient enrolment by end of 2013 and unblinding of trial data in the first half of 2014 [8].
Sep 12Sunesis Pharmaceuticals, Inc. today announced that it will implement a one-time, 225-patient sample size increase to its Phase 3 VALOR trial bringing target enrollment to 675 patients. This is in response to the recommendation of the trial´s independent DSMB [7].
Apr 12As of March 2012, 260 pts have already enrolled in the VALOR trial. In December 2011, the Data and Safety Monitoring Board (DSMB) recommended the trial continue as planned. An interim analysis is expected to take place in the third quarter of 2012, with unblinding anticipated in mid-2013 [4].
Dec 10The PIII VALOR trial of vosaroxin in combination with cytarabine in patients with first relapsed or refractory acute myeloid leukemia (AML) has started. The multinational, randomized, double-blind, placebo-controlled trial will enroll 450 evaluable patients at sites in the US Canada, Europe, Australia and New Zealand. The primary endpoint is overall survival. The trial has an adaptive design that provides for a single interim analysis by an independent Data and Safety Monitoring Board which will decide whether to implement a one-time sample size adjustment of 225 additional evaluable patients to maintain adequate power across a range of outcomes. The interim analysis is expected to take place mid-2012 [2].
Jun 10The company has received advice from the EMA and the FDA on its proposed PIII study in patients with first relapsed or primary refractory AML. Based on feedback from the two agencies, the company expects that if the study demonstrates a convincing increase in overall survival (primary endpoint) and a favourable benefit-risk ratio it will be sufficient for registration in US and EU. It plans to start the multi-national, double-blind trial in 2H 2010. The trial will enrol around 450 patients who will be randomised to either voreloxin (90mg/m2) on days 1 and 4 in combination with cytarabine (1g/m2) daily for 5 days, or placebo in combination with cytarabine [1].
Jun 10Voreloxin is currently being evaluated in a fully enrolled single agent PII study (REVEAL-1) in previously untreated elderly AML patients and in a fully enrolled PIb/II study combining voreloxin with cytarabine for the treatment of patients with relapsed/refractory AML. (A PII single agent trial in platinum-resistant ovarian cancer has also completed enrollment.) [1]
Jun 10Voreloxin is a first-in-class anticancer quinolone derivative (AQD). It intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis [1].

Evidence based evaluations