The US Food & Drug Administration has granted Orphan Drug Designation to Mirati Therapeutics' mocetinostat, the company's spectrum selective HDAC inhibitor for the treatment of myelodysplastic syndrome (MDS).

Mocetinostat is being developed in phase 2 clinical studies in combination with Vidaza as a treatment for intermediate and high-risk MDS, as well as a single agent treatment in patients with diffuse large B-cell lymphoma (DLBCL) and bladder cancer targeting specific genetic mutations in histone acetylation that increase the likelihood of response in tumor cells.

"Orphan designation is an important piece of the development plan for mocetinostat as we evaluate combination and single agent clinical development opportunities for the programme," said Dr Charles Baum, president and CEO of Mirati. "We are excited about the opportunity to identify and select patients whose cancers may be especially sensitive to mocetinostat, and we expect to have initial data from Phase 2 studies by the end of the year which will allow us to move quickly into a registration path."

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.

"HDAC inhibitors may significantly increase the efficacy of other epigenetic agents such as inhibitors of LSD1, EZH2 and DOT1L as well as hypomethylating agents such as Vidaza in the treatment of MDS and other malignancies," added Baum. "Epigenetic pathways can become dysregulated during cancer progression through a variety of mechanisms, including the genetic alteration of pathways that control DNA methylation and histone modification. These alterations often result in silencing of selected tumor suppressor genes and uncontrolled tumor growth in certain malignancies including MDS, lymphomas and solid tumors such as bladder cancer."

Mocetinostat is an orally-bioavailable, spectrum-selective HDAC inhibitor. In addition to the ongoing phase 2 clinical trials, 13 clinical trials have been completed, which enrolled over 400 patients with a variety of hematologic malignancies and solid tumours. 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.

Mirati Therapeutics is a targeted oncology company developing an advanced pipeline of breakthrough medicines for precisely defined patient populations.