The Oncologic Drugs Advisory Committee ( ODAC ) of the U.S. Food and Drug Administration ( FDA ) recommended approval of Revlimid ( Lenalidomide ) for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes ( MDS ) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

The Committee based its recommendation on clinical data from an open label Phase II trial, evaluating Revlimid in the largest trial with MDS patients with deletion 5q chromosomal abnormality to date.

The data showed that:

- approximately two-thirds of patients achieved resolution of chronic refractory anemia resulting in transfusion independence
- response was associated with meaningful cytogenetic and bone marrow remission
- responder median hemoglobin increased more than 5.0 grams per deciliter
- after median follow-up of 58 weeks, the median duration of transfusion-independence response had not yet been reached

The dosing in the study was based on tolerability and additional studies are planned to refine dosing

The major side effects were cytopenias leading to dose reductions.

Revlimid is a member of a new class of novel IMiDs, immunomodulatory drugs.

Celgene continues to evaluate treatments with Revlimid for a broad range of hematology and oncology conditions, including; multiple myeloma, the malignant blood cell disorders known as myelodysplastic syndromes ( MDS ), chronic lymphocytic leukemia as well as solid tumor cancers.

Chromosomal abnormalities are detected in more than half of patients with myelodysplastic syndrome ( MDS ), and involve 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% of all MDS patients.
The World Health Organization ( WHO ) 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.

ODAC evaluated the Revlimid NDA for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes ( MDS ) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
Both Celgene and the FDA presented the results of the open label Phase II ( MDS-003 ) trial data.

These questions were voted upon by the Committee:

Question 1: Randomized controlled trials allowed for direct comparisons of treatment effects and safety between treatment arms. A single arm study has been submitted using an 8-week run-in period to serve as a baseline for each patient's transfusion requirements. A comparison is subsequently made to a follow-up 8-week period on Revlimid to compare transfusion requirements. Does this study design allow adequate characterization of Revlimid 's treatment effect in the population described in the proposed indication ? Vote 11 Yes - 4 No

Question 2: In this single arm trial, 80% of patients enrolled in MDS- 003 has dose reductions and/or delays and 80% of patients experienced either grade 3 or 4 adverse events. Data do not exist on the efficacy and safety of lower Revlimid doses. Approval of a drug is contingent upon being able to write adequate product labeling, requiring a recommended dose and characterization of a safety profile. Do the data provided in this single-arm trial provide a basis for a recommendation dose and adequate description of a safety profile ? Vote 2 Yes -13 No

Source: Celgene, 2005


XagenaMedicine2005