Cyclacel Pharmaceuticals, Inc., a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious diseases, announced that it has reached agreement with the US Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a pivotal phase 3 trial for the company's sapacitabine oral capsules as a front-line treatment in elderly patients aged 70 years or older with newly diagnosed acute myeloid leukaemia (AML) who are not candidates for intensive induction chemotherapy.

"The SPA agreement with FDA represents an important milestone for Cyclacel and provides a clear registration pathway for sapacitabine," said Spiro Rombotis, president and chief executive officer of Cyclacel. "If it reaches the market, sapacitabine would be the first orally-administered drug to be offered to this patient population with the potential to serve as induction, consolidation and maintenance treatment of this life-threatening disease. In addition to progressing to phase 3 in AML, we look forward to reporting sapacitabine phase 2 data in myelodysplastic syndromes (MDS) and non-small cell lung cancer (NSCLC)."

The phase 3, registration-directed, clinical trial of sapacitabine oral capsules to be conducted under the SPA will be a randomized study against an active control drug with the primary objective of demonstrating an improvement in overall survival. Sapacitabine will be administered as an outpatient treatment. Cyclacel plans to begin patient enrolment in this phase 3 trial before the end of 2010. Additional information on the design of the trial will be provided after initiation of the study.

"We are pleased to receive the SPA Agreement letter from the FDA stating that the design and planned analysis of the pivotal phase 3 study adequately address the objectives necessary to support the submission of a New Drug Application (NDA)," said Judy Chiao, M.D., vice president of clinical development and regulatory affairs of Cyclacel. "AML in the elderly is a life-threatening disease with high unmet medical need. Patients with AML aged 70 years or older have a poor prognosis as the majority of these patients are not candidates for intensive induction chemotherapy because of poor tolerability to such therapy and a high risk of relapse because of the lack of effective consolidation and maintenance therapy. We will now concentrate our efforts on initiating the phase 3 study in AML in collaboration with our clinical investigators."

In addition to the Cyclacel-sponsored trials of sapacitabine, the company has been approached by cooperative groups seeking to conduct, largely at their expense, investigator-initiated studies of sapacitabine with alternative study designs.

A Special Protocol Assessment is a binding written agreement with the FDA that the sponsor's proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support regulatory approval. Final marketing approval depends on efficacy results, adverse event profile and an evaluation of the benefit/risk of a treatment as demonstrated in the trial.

Sapacitabine (CYC682), an orally-available nucleoside analogue, is currently being evaluated in Phase 2 trials in patients with haematological malignancies and solid tumours. Sapacitabine acts through a dual mechanism, interfering with DNA synthesis by causing single-strand DNA breaks and inducing arrest of cell cycle progression mainly at G2-phase. Both sapacitabine and CNDAC, its major metabolite, have demonstrated potent anti-tumour activity in preclinical studies. Over 200 patients have received sapacitabine in Phase 2 studies in AML, MDS, cutaneous T cell lymphoma (CTCL) and non-small cell lung cancer (NSCLC). Sapacitabine has been administered to approximately 170 patients in five phase 1 studies with both haematologic malignancies and solid tumours. In December 2009 at the 51st Annual Meeting of the American Society of Hematology (ASH), Cyclacel reported data from a randomized phase 2 study including promising 1-year survival in elderly patients with AML aged 70 years or older. Sapacitabine is part of Cyclacel's pipeline of small molecule drugs designed to target and stop uncontrolled cell division.

Cyclacel is a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious diseases.