Hybrigenics, a Paris-based biopharmaceutical company, has received Orphan Drug designation by the FDA for inecalcitol for the treatment of acute myeloid leukemia (AML) in the U.S. Orphan designation qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing.

This favorable decision is based on in vitro and in vivo preclinical evidence showing the synergy between inecalcitol and azacytidine or decitabine, two hypo-methylating anticancer drugs, to inhibit the growth of human AML cell lines to prolong the survival of mice in two different experimental models of AML.

Azacytidine (Vidaza, Celgene) and decitabine (Dacogen, Janssen-Cilag) are two hypo-methylating agents already used for AML in older (>65 years old) or frail patients not eligible to standard induction chemotherapy. Inecalcitol alone already has been studied in a phase II clinical trial in chronic lymphocytic leukemia: an inhibitory effect has been shown in half of the treated patients. Another phase II clinical study has recently been launched in combination with imatinib (Gleevec, Novartis) in chronic myeloid leukemia.

“We are actively preparing an additional clinical phase II study of inecalcitol in combination with either azacytidine or decitabine in older or frail AML patients, in France as well as in the U.S.,” said Jean-François Dufour-Lamartinie, Hybrigenics’ head of clinical R&D.

Worldwide, AML is the second-most frequent form of leukemia (behind chronic lymphocytic leukemia) and accounts for about 30% of all leukemic patients. In the U.S., it recently has become the most frequent one with 36% of all newly diagnosed leukemia cases. AML is designated as an orphan disease in the U.S., Europe and Japan.

AML can occur at any age but is more common in adults over the age of 60. Treatment needs to begin soon after AML is diagnosed, as it progresses very quickly. Chemotherapy is the main form of treatment for AML; occasionally, a stem cell transplant may be used. Despite available treatments, AML shows the lowest five-year survival rate of all leukemias: 25% in the U.S. and 19% in Europe.