Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announced that its novel hypomethylating agent, guadecitabine (SGI-110), has been granted an orphan drug designation by the US FDA.

Guadecitabine has been evaluated in multiple phase 1 and phase 2 trials to investigate its potential in the treatment of a range of cancers. The company has recently completed a large (over 400 patients) randomized phase 1/2 study in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). The trial included a phase I dose escalation stage (93 patients) and a randomized phase 2 stage (308 patients) that investigated four different patient populations: treatment naïve and relapsed/refractory AML and MDS. The trial demonstrated that guadecitabine was clinically active and well tolerated in all four patient groups. The results from the phase 1 portion of the trial were recently published in Lancet Oncology.

Guadecitabine is now being evaluated in the ASTRAL-1 trial, a large, global, randomized 800-patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine.

Mohammad Azab, Astex’s president and chief medical officer said, “We are delighted that FDA has granted orphan drug status to guadecitabine for the treatment of AML. This designation supports our conviction that new therapies are desperately needed for patients who are diagnosed with AML, particularly those for whom standard intensive induction chemotherapy is unsuitable, and helps underpin the rationale for commencing the ASTRAL-1 trial, the largest clinical study ever conducted in this group of patients.”

Orphan Drug designation is granted to drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 people in the US. Orphan Drug designation by the FDA qualifies the sponsor for incentives provided for in the Orphan Drug Act, which can include protocol assistance for clinical trials, prescription drug user fee waivers, tax incentives and seven years of market exclusivity.

AML is the most common hematological malignancy in adults. Over 20,000 new cases of AML are diagnosed annually in the US. Although 60per cent-75 per cent of AML patients <60 years of age will achieve complete response (CR) with standard intensive induction chemotherapy, approximately 30 per cent-40 per cent of patients will die from their disease. The outlook for patients >60 years old is significantly worse with response rates < 50 per cent, cure rates remaining at <10 per cent and a median survival of <1 year. These figures have not significantly improved within the last 3 decades. These patients have few therapeutic options. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients whose comorbidities make them unfit for intensive therapy.

Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active moiety, decitabine, compared to iv decitabine and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients.