Cyclacel’s leukemia drug for elderly patients fails in phase 3 trial

Sapacitabine (CYC682), an orally-available nucleoside analogue, acts via a novel DNA single-strand breaking mechanism, resulting in production of DNA double strand breaks (DSBs) and/or checkpoint activation.

Primary endpoint of the phase 3 trial dubbed, SEAMLESS, was statistically significant improvement in overall survival (OS) which wasn’t reached by the experimental arm in comparison to the active control.

Following the negative top-line results of the trial, Cyclacel would reassess its continued investment in sapacitabine in blood cancer.

Cyclacel president and CEO Spiro Rombotis said: "We are disappointed not to have reached the primary endpoint of SEAMLESS. Nevertheless, the improvement in CR rate and similar safety profile are encouraging.

“We plan to discuss the data with European and US regulatory authorities once subgroup analyses are completed over the next few months and will report our further plans as they develop.”

The trial was carried out in 70 years or older newly diagnosed acute myeloid leukemia (AML) patients who are not suitable or have refused intensive induction chemotherapy.

Sapacitabine, a CDK2/9 inhibitor administered orally with intravenous decitabine in alternating cycles was pitted against an active control arm of intravenous decitabine, subjected alone.

One of the secondary endpoints defined as improved rate of complete remission (CR) was noted in patients who had stopped treatment at the time of the study.

The trial's findings revealed that there wasn’t much of a difference for the other endpoints between the two arms.

The company added that there was an improvement in OS for a stratified patient subgroup subjected to the sapacitabine treatment. This group represented nearly two-thirds of the trial’s population and having low baseline peripheral white blood cell count.

On the other hand, the sapacitabine treatment did not show any OS improvement in patients with high white blood cell count.