CytRx Corporation, a biopharma R&D company engaged in the development of high-value human therapeutics, has announced that its lead drug candidate tamibarotene has received official notification from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMEA) that a positive opinion was made regarding the application for orphan medicinal product for the treatment of acute promyelocytic leukaemia (APL).
The positive opinion of the COMP has now been forwarded to the EU commission for final approval and publication in the community register. This favourable opinion for tamibarotene in the EU is in addition to the Orphan Drug Designation for APL and Fast Track Designation for the treatment of adult patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide granted by the US FDA in October 2007.
"We believe that the positive opinion by the COMP reflects the potential therapeutic value of tamibarotene as a treatment for European patients suffering from APL, especially for those who currently lack an effective third-line therapy for their disease. We consider this positive opinion important as it supports our ability to pursue marketing approval for tamibarotene in the EU in addition to our ongoing U.S. clinical program," said Steven A. Kriegsman, CytRx president and CEO.
CytRx chief scientific officer Jack Barber, commented, "The granting of orphan medicinal product status for tamibarotene will provide us with an improved communications mechanism with the European Medicines Agency (EMEA) and other EU regulatory officials going forward as we pursue EU approval. Added interaction between the EMEA and CytRx during the regulatory process could assist us in obtaining marketing approval for tamibarotene for the treatment of APL in the EU."
The European Commission grants orphan medicinal product status to promote the innovation of drugs that are developed to treat, prevent or diagnose diseases or conditions that affect no more than five in 10,000 persons in the EU. With this designation, CytRx will have market exclusivity in the EU for 10 years in the event that tamibarotene receives marketing approval. The designation also provides for special benefits, including research support, eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees during development, or at the time of application for marketing approval.
Acute promyelocytic leukaemia (APL) is a subtype of acute myelogenous leukaemia, a cancer of the blood and bone marrow. In APL, an abnormal accumulation of immature granulocytes called promyelocytes in the bone marrow results in a reduction in the production of normal red blood cells and platelets, resulting in anaemia and thrombocytopenia. Either leukopenia (low white cell count) or leukocytosis (high white cell count) may be observed in the peripheral blood. Symptoms include fatigue, weakness, shortness of breath from anaemia, easy bruising and bleeding from thrombocytopenia and coagulopathy, and fever and infection from lack of normal white blood cells.
CytRx holds the North American and European rights to tamibarotene as a treatment for APL. Tamibarotene is an orally available, rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects by binding to its molecular target more selectively than all trans-retinoic acid (ATRA), the current first-line treatment for APL. The FDA has granted Orphan Drug Designation for APL and Fast Track Designation for the treatment of adult patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. There are currently no third-line treatments for APL approved in the US or Europe.
A Special Protocol Assessment (SPA) is in place with the FDA for a phase 2 registration clinical trial, known as STAR-1, which is evaluating the efficacy and safety of tamibarotene as a third-line treatment for APL. The STAR-1 trial is ongoing and currently includes seven clinical sites in the U.S. CytRx believes that successful data from the STAR-1 trial and supporting studies, in conjunction with data from the Japanese clinical trials, will form the basis for a New Drug Application (NDA). CytRx recently reported that, of the 11 patients enrolled in the STAR-1 trial to date, 5 patients, or 45%, achieved a morphologic leukaemia-free state, or MLFS. Of those, two patients have achieved durable complete response and one has achieved morphologic leukaemia-free state, or MLFS, but withdrew from the trial to receive a bone marrow transplant before the durable complete response could be confirmed. One patient achieved a complete response, but did not maintain MLFS for the required 28 days to be considered a durable complete response. Another patient achieved a durable MLFS, but did not have the necessary increases in blood cells to be considered a durable complete response.
The efficacy of orally administered tamibarotene was demonstrated in two Phase 2 studies conducted in Japan in a total of 63 Japanese subjects with APL. The overall complete response rate in these subjects was 60%. In subjects experiencing their first relapse, the overall complete response rate was 81%. Tamibarotene is currently approved in Japan as a treatment for relapse APL.
CytRx also retains an option to expand its licenses for the use of tamibarotene in other fields in oncology, including multiple myeloma, myelodysplastic syndrome and certain solid tumours in the US, and multiple myeloma, myelodysplastic syndromes and solid tumours other than hepatocellular carcinoma in Europe. Tamibarotene also has showed statistically significant anti-tumour activity in animal trial for multiple myeloma, an incurable malignant tumour of the plasma cells of bone marrow.