The US Food and Drug Administration (FDA) has granted Orphan Drug Designation to Mirati Therapeutics' mocetinostat, a spectrum selective HDAC inhibitor, for diffuse large B-cell lymphoma (DLBCL). In June, mocetinostat was granted Orphan Drug Designation as a treatment for myelodysplastic syndrome (MDS).  Orphan drug designation is also being sought for bladder cancer patients with specific genetic alterations.

Mocetinostat is being developed as a single agent treatment in patients with diffuse large B-cell lymphoma (DLBCL) and bladder cancer with specific genetic mutations in Histone Acetyl Transferases (HATs) that we believe to be critically involved in the pathogenesis and progression of these tumour types.  Mocetinostat reverses aberrant acetylation resulting from HAT mutations and is predicted to halt tumour progression and reduce tumour burden in patients. Mocetinostat is also in phase 2 clinical studies in combination with Vidaza as a treatment for intermediate and high-risk MDS.

"We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one third of DLBCL and bladder tumours. Nonclinical tumour models exhibiting these mutations are particularly responsive to mocetinostat," said Dr Charles Baum, president and chief executive officer, of Mirati. "Among other benefits, orphan designation provides seven years of market exclusivity to target these genetically defined patients with unmet medical need in the event we achieve regulatory approval."

The FDA's Office of Orphan Drug Products grants orphan status to support development of medicines for underserved patient populations or rare disorders that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

Mocetinostat is an orally-bioavailable, spectrum-selective HDAC inhibitor. Mocetinostat is enrolling patients in a Phase 2 dose confirmation study in combination with Vidaza as treatment for intermediate and high-risk MDS. Mirati also plans to initiate phase 2 studies of mocetinostat as a single agent in patients with mutations in histone acetyl transferases in bladder cancer and DLBCL. Initial data from the phase 2 studies is expected by the end of 2014. In addition to the ongoing phase 2 clinical trials, mocetinostat has completed 13 clinical trials in more than 400 patients with a variety of hematologic malignancies and solid tumours.