Cyclacel Pharmaceuticals’ sapacitabine fails to meet primary endpoint in Phase 3 blood cancer trial

Cyclacel Pharmaceuticals, a New Jersey-based biopharmaceutical company, announced that its experimental blood cancer drug, sapacitabine (CYC682), did not meet the primary endpoint in the pivotal phase 3 SEAMLESS study. The trial aimed to evaluate the effectiveness of sapacitabine in elderly patients over 70 years old who are newly diagnosed with acute myeloid leukemia (AML) and are unfit or unwilling to undergo intensive induction chemotherapy.

Trial Outcome and Future Plans

The orally-administered nucleoside analogue, sapacitabine, was tested in combination with decitabine, administered intravenously in alternating cycles. However, it failed to show a statistically significant improvement in overall survival (OS) compared to decitabine alone. Spiro Rombotis, President and CEO of Cyclacel, expressed disappointment but noted encouraging aspects of the trial, such as the improved complete remission (CR) rates and a similar safety profile.

“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,” said Rombotis. He also emphasized the company’s gratitude towards clinical investigators, patients, and their families for their contributions to the study.

Analysis and Strategic Shift

Despite the setback, Cyclacel Pharmaceuticals plans to reevaluate its investment in sapacitabine for treating hematological malignancies. The company will now focus more on its ongoing clinical programs related to DNA damage response and transcriptional regulation, including their expertise in CDK inhibitors.

Hagop Kantarjian, M.D., Professor and Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center and chair of the SEAMLESS study, remarked on the findings: “Although the experimental arm of alternating decitabine-sapacitabine did not reach statistically significant superiority in overall survival, it is remarkable that an improvement in complete remission rate was observed.”

Subgroup Findings and Implications

The trial also highlighted that overall survival improved in a stratified patient subgroup who received sapacitabine. This subgroup comprised patients with low baseline peripheral white blood cell counts, who constituted two-thirds of the patient population in the trial. Conversely, no improvement in overall survival was seen in patients with high white blood cell counts.

Cyclacel’s approach leverages sapacitabine’s mechanism as a second-generation CDK2/9 inhibitor that induces DNA double-strand breaks and/or checkpoint activation through a novel DNA single-strand breaking mechanism. However, further analyses are needed to fully understand the potential and limitations of sapacitabine in different patient subgroups.

Looking Ahead

With the drug failing to achieve the desired results in the phase 3 trial, Cyclacel Pharmaceuticals is poised to reconsider its future investments in developing sapacitabine as a viable therapy for blood cancer, focusing instead on other promising areas within its portfolio.