Orphan Drug Designation Received for Acute Leukemia Treatment

Epizyme, Inc., a clinical stage biopharmaceutical company, has announced that it received FDA orphan drug designation for its treatment for acute leukemias in which the myeloid/lymphoid, or mixed-lineage, leukemia (MLL) gene is rearranged due to a chromosomal translocation (MLL-r).

MLL-r leukemia is an aggressive subtype of two of the most common forms of acute leukemia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). There are presently no approved therapies for MLL-r leukemia.

Epizyme‘s proprietary product platform creates small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases (HMTs), which are part of the system controlling gene expression. Genetic alterations can result in changes to HMT activity, making them cancer-causing. By focusing on the genetic drivers of cancers, Epizyme is attempting to bring a personalized approach to cancer treatment by matching the right treatments with the right patients.


The orphan treatment, EPZ-5676, is a small molecule inhibitor of DOT1L HMT. Epizyme initiated Phase 1 clinical trials for EPZ-5676 in September 2012. According to Epizyme, EPZ-5676 is the first HMT inhibitor to enter human clinical trials. Epizyme reports that the orphan treatment is now in the dose escalation phase and they expect to initiate an expansion phase in the second half of 2013 that will exclusively enroll MLL-r patients.

Epizyme’s research on EPZ-5676 was published in the journal Blood in a paper titled “Potent Inhibition of DOT1L as Treatment for MLL-Fusion Leukemia,” authored by Roy M. Pollock, Scott R. Daigle, Edward J. Olhava and colleagues at Epizyme. According to the paper, continuous intravenous infusion of EPZ-5676 in a rat xenograft model of MLL-r leukemia caused complete tumor regressions that were sustained well beyond the compound infusion period with no significant weight loss or signs of toxicity.

Partnerships with Epizyme

While Epizyme owns all rights to EPZ-5676 in the United States, it has granted Celgene Corporation an exclusive license to EPZ-5676 outside of the United States. Epizyme also granted Celgene the option to license rights outside the United States to other HMT programs, excluding HMT targets covered by its two other existing therapeutic collaborations. Under the agreement, Epizyme is eligible to receive royalties on net product sales outside of the United States.

Epizyme has also entered into an agreement with Abbott Laboratories under which it agreed to fund Abbott’s development of a companion diagnostic test to identify patients with the MLL-r genetic alteration.

Orphan Designation

The FDA’s Orphan Drug Designation Program provides orphan status to drugs and biologics which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. Orphan drug designation allows special incentives for sponsors, including tax credits, research and development grant funding, reduced filing fees during development or at the time of application for marketing approval, and up to seven years of marketing exclusivity independent of any other intellectual property interests.

According to a report by Clarion Healthcare, LLC, commissioned by Epizyme, the total annual incidence of MLL-r in all pediatric and adult patients suffering from AML and ALL is approximately 4,900 patients.