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NDA submitted to FDA for MDS

12-Apr-2005

Celgene has announced it has submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for its investigational drug Revlimid, a first in a new class of novel immunomodulatory drugs, or ImiDs.

Revlimid affects multiple intracellular biological pathways and is being evaluated for treating a broad range of haematology and oncology conditions, including; multiple myeloma, the malignant blood cell disorders known as myelodysplastic syndromes (MDS) as well as solid tumour cancers.

Celgene's growing reputation in the oncology franchise suggests that Revlimid has good opportunity to realise commercialisation. However, Revlimid will face stiff competition from other novel agents submitted to the FDA for the same indication.

 

Celgene has no approved marketed oncology products, though thalidomide's off-label use in multiple myeloma will have given Celgene some degree of experience in the oncology field. Revlimid's favourable clinical activity and reduced toxicity, combined with the convenience of one-daily oral administration and Celgene's growing reputation in the multiple myeloma franchise, suggest that Revlimid has good opportunity to realise commercialisation.

 

IMiDs, exert their anti tumour properties by modulation of tumour necrosis factor alpha. Revlimid is a derivative of Celgene's flagship product, thalidomide. Revlimid has been demonstrated to be more powerful than thalidomide in multiple myeloma and has a much improved toxicity profile. More importantly, Revlimid does not have the devastating teratogenic effects of thalidomide.

 

The progress of this drug gives hope to the sufferers of this disease. Because of the rarity of this disorder, MDS patients represent a clinically underserved population where agents that reduce transfusion dependence and prevent or delay progression to AML are required.

 

MDS is a malignant disorder of blood cell production that affects approximately 300,000 people worldwide. The most common clinical manifestation associated with MDS is refractory anaemia, and the multiple complications that stem from frequent blood transfusions.

 

The company's NDA is seeking approval to market Revlimid as a treatment for transfusion-dependent patients with myelodysplastic syndromes (MDS) with a 5q deletion chromosomal abnormality. This is after clinical data from Phase II trial (MDS-003) in patients with myelodysplastic syndromes with 5q deletion chromosomal abnormality submitted.

 

Chromosomal (cytogenetic) abnormalities in the preliminary trials demonstrated that transfusion independence was achieved in 64 per cent of patients. This involved a deletion in all or part of one or more specific chromosomes. The most common cytogenetic abnormalities in MDS are deletions in the long arm of chromosomes 5, 7, and 20.

 

Another common abnormality is an extra copy of chromosome 8. A deletion involving the 5q chromosome may be involved in 20 to 30 per cent of all MDS patients. The World Health Organisation has also recently identified a unique subset of MDS patients with a "5q- Syndrome" where the only chromosomal abnormality is a specific portion of the 5q chromosome.

 

"Celgene appreciates and acknowledges the efforts of all those who made this filing possible, including: the more than 400 patients who participated in these MDS studies, and the international community of clinical investigators who have helped us get to this stage in the regulatory process." said Jerome Zeldis, chief medical officer and VP, medical affairs of Celgene.

 

Myelodysplastic syndromes (MDS) are a group of haematological malignancies that affect approximately 300,000 people worldwide. Myelodysplastic syndromes occur when blood cells remain in an immature or "blast" stage within the bone marrow and never develop into mature cells capable of performing their necessary functions.

 

Eventually, the bone marrow may be filled with blast cells suppressing normal cell development. According to the American Cancer Society, 10,000 to 20,000 new cases of MDS are diagnosed each year in the United States, with mean survival rates ranging from approximately six months to six years for the different classifications of MDS.

 

MDS patients must often rely on blood transfusions to manage symptoms of anaemia and fatigue until they develop life-threatening iron overload and/or toxicity, thus underscoring the critical need for new therapies targeting the cause of the condition rather than simply managing its symptoms.

 

There are no approved IMiDs at present and there remain, therefore, a number of regulatory and marketing hurdles for Celgene to clear before Revlimid could gain approval. Given these circumstances Revlimid will face stiff competition from other therapies in both markets.

 

Within the multiple myeloma market a range of rival novel therapies will compete with Revlimid, such as Millennium Pharmaceuticals' already-approved Velcade (bortezomib) and, within MDS, MGI Pharma's Dacogen (decitabine).