Sunesis Pharmaceuticals has announced disappointing results from its Phase III trial of Qinprezo, a drug designed to treat acute myeloid leukaemia (AML), meaning the drug may fail to get approval. The results, which were revealed at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in May, represent a huge setback for the pharmaceutical company.
Sunesis revealed the results from its VALOR trial, which had performed a post-hoc analysis of 91 elderly patients, aged 60 and above, with relapsed/refractory (R/R) AML. Initially, VALOR had displayed a positive trend toward improvement in overall survival (OS) when patients received Qinprezo in combination with cytarabine. However, overall results are more in keeping with findings revealed by the company In December 2014 at the 56th Annual Meeting of the American Society of Haematology (ASH). At that stage, Qinprezo failed to meet its primary OS endpoint by a slim margin.
Given these disappointing results, the question at this point is: what does the future hold for Qinprezo? The path forward for the drug is certainly not clear, although Sunesis holds an orphan drug designation for Qinprezo from both the FDA and the European Commission (EC), and a fast track designation from the FDA. However, another Phase III confirmatory clinical trial will most likely be required in order to successfully bring the drug to market. Furthermore, GlobalData expects that Sunesis will now face difficult financial hurdles in order to fulfill the regulatory requirements needed for approval. Following suit from other recent oncology collaborations, partnering with a bigger pharmaceutical player, such as the blood cancer specialist, Celgene, is likely to be Sunesis’ best bet to secure the future potential of Qinprezo in the older R/R AML patient subgroup.
While AML is an indication with overwhelmingly high unmet needs, the pipeline for the disease has remained sparse until recent years. Qinprezo is a first-in-class molecule and an anti-cancer quinolone derivative (AQD). The drug was considered a prime candidate in the AML pipeline, as it targets the R/R subgroup of AML patients, who have high unmet needs. VALOR is one of the largest trials in this setting and with a total of 711 patients enrolled across 124 study sites it received widespread coverage and generated high expectations within the field. Thus, key opinion leaders (KOLs) will no doubt be disappointed with the delay in the drug’s development.
The VALOR trial was split between younger (age 18-59 years) and older (age =60 years) R/R AML patients, with 260 and 451 patients in the each respective subgroup. Previous data presented at ASH showed a median OS of 7.5 months for Qinprezo/cytarabine, compared with 6.1 months for placebo/cytarabine, when analyzed in both younger (age 18-59 years) and older (age =60 years) R/R AML patients, although this slight six-week difference was not statistically significant (p=0.06). Following age stratification, the younger relapsing AML patients had no significant OS improvement. A statistically significant difference in median OS was found after censoring for transplant in all patients that received Qinprezo (6.7 months for Qinprezo versus 5.3 months placebo (Hazard Ratio [HR] = 0.809, p=0.02). However, this OS difference of 1.4 months is hard to interpret as clinically meaningful. The post-hoc results presented at ASCO demonstrated that the median OS for older patients who underwent HCT was 20.2 months on the vosaroxin/cytarabine arm, versus 12.2 months on the placebo/cytarabine arm ([HR] = 0.699; one-sided p=0.18).
In the latest post-hoc analysis, although Qinprezo demonstrated a high rate of pre-transplant complete remission (CR) and encouraging survival outcomes for older patients, the patient subgroup was considerably small. As the majority of elderly unfit AML patients are also not eligible for HCT, this could ultimately narrow the patient pool able to receive Qinprezo when it is used in a pre-transplant setting. Should the regulatory bodies require another confirmatory trial in the older AML patient subgroup it will no doubt be disappointing for all involved.