July 28, 2008

Takeda/J&J: EU Recommendation Positions Velcade for First-Line Myeloma Approval

Velcade is likely to receive EMEA approval following a positive opinion issued by the EU Committee for Medicinal Products for Human Use for use in previously untreated multiple myeloma patients. Velcade would see considerable uptake if the drug is approved in the first-line setting, due to its proven activity and favorable safety profile compared to current treatment regimens.

Velcade (bortezomib; Takeda/Johnson & Johnson) has received a positive opinion from the EU Committee for Medicinal Products for Human Use (CHMP) for use as first-line therapy in combination with melphalan and prednisone in multiple myeloma patients who are ineligible for high-dose chemotherapy with bone marrow transplant. In June 2008, Velcade received FDA approval for label expansion in this indication based on findings from a Phase III trial.

In the randomized trial (known as VISTA - Velcade as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone), the combination of Velcade, melphalan and prednisone (VMP) was compared to melphalan and prednisone (MP) in 682 newly-diagnosed multiple myeloma patients ineligible for stem cell transplantation. Time-to-progression was statistically higher in the VMP arm, at 24 months, compared to 16.6 months in the MP arm. Safety and tolerability were as expected for VMP. The trial was halted in September 2007 to allow crossover of patients in the MP arm to the VMP arm of the study.

Velcade is a small molecule, reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome inhibitor. The 26S proteasome is a large protein complex responsible for degrading ubiquitinated proteins in mammalian cells. Velcade inhibition disrupts normal cell mechanisms to cause subsequent cell death.

The drug is approved in the US, EU and Japan as a second-line treatment for multiple myeloma. It is also approved in the US as a second-line treatment for mantle cell lymphoma. It now appears likely that Velcade will receive EU approval for first-line use in multiple myeloma, given the high level of efficacy demonstrated and the degree of unmet need which persists in this indication.

The incidence of multiple myeloma in the seven major pharmaceutical markets is around 40,000. Average overall survival for the disease ranges from three to six years, and, due to the high proportion of patients who suffer relapse, unmet need is high.

In the EU, the current first-line treatment regimen for patients who are not candidates for stem cell transplantation is MPT, the combination of Celgene's Thalomid (thalidomide), melphalan and prednisone, which is also approved in the US. Velcade is now set to compete with Thalomid for a share of the market in the EU, where it is likely to mount a strong challenge because of the high toxicity associated with the MPT regimen.