BEERSE, Belgium, June 14 /PRNewswire/ --
- 30 Percent Complete Response Rate Compared to 4 Percent With Current Drug Treatment Standard of Care
- Abstract Number: 0473
Janssen-Cilag / Ortho Biotech, the biopharmaceutical division of Janssen- Cilag, today announced unprecedented results from a registration-enabling phase III trial evaluating the VELCADE-based therapy with melphalan and prednisone (VMP) compared with melphalan and prednisone (MP) alone, for previously untreated patients with multiple myeloma (MM) who are not eligible for stem cell transplantation. The study showed VMP achieves superior complete response rates which are significantly durable and may be prolonged with continued therapy after the initial complete response is achieved. The three-year survival rate with VMP was 72 percent versus 59 percent with MP.
"VELCADE continues to demonstrate value as a standard of care that can slow or halt the progression of multiple myeloma across all stages of the disease, especially in previously untreated patients," said Professor Jesus San Miguel, MD, University Hospital of Salamanca in Spain, and principal investigator for the trial. "It is estimated that up to 60 percent of patients are not eligible for transplant. The high overall and complete response rates achieved in this trial correlated with the duration of response as well as prolonged survival, representing a significant advance in treatment."
The study was featured as one of the five best abstracts at the Presidential Symposium during the European Haematology Association (EHA) 13th Congress in Copenhagen, Denmark, 12th - 15th June.
VISTA Study Results
The randomised, international, open-label phase III VISTA (VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone) study compared VMP with MP as a treatment for previously untreated patients who were not eligible for stem cell transplantation. The primary endpoint was time-to-progression, with secondary endpoints including: response rates, time to and duration of response, progression free and overall survival, safety, and clinical benefit by time to next therapy. Of 682 randomised patients (VMP=344, MP=338) who received up to 54 weeks of treatment, results included:
- Overall response rate of 71 percent with VMP versus 35 percent with MP (p<10-6)
- Complete response rate (CR) with VMP of 30 percent compared to four percent CR (p<10-6) - Median time to response of 1.4 months with VMP compared to 4.2 months with MP (p<10-10); median time to CR was 4.2 months with VMP compared to 5.3 months with MP (p<10-10) - Median duration of response was 19.9 months with VMP compared to 13.1 months with MP; for patients achieving CR the median duration of response was 24 months with VMP, versus 12.8 months for MP, allowing patients a greater opportunity for a treatment-free interval
- The three-year survival rate was 72 percent with VMP, versus 59 percent with MP, resulting in a 36 percent reduced risk of death; median overall survival had not been reached with either regimen (p=0.0032)
- Median time-to-progression of 24 months with VMP, compared to 16.6 months with MP (p=0.0000001), resulting in a 52 percent reduced risk of progression
- Median time to next therapy had not been reached with the VMP regimen versus 20.8 months with MP (p=0.000009)
- These results were consistent across all prognostic subgroups, including patients with poor prognostic characteristics
- Safety and tolerability were consistent with known VELCADE, melphalan and prednisone profiles
- Results were evaluated using a central laboratory for M-protein level assessment, and both response and progression were assessed every three weeks
In September 2007, the VISTA trial was halted based on an independent data monitoring committee (IDMC) recommendation that found the study had crossed the pre-specified boundary for the primary endpoint of time-to-progression. Upon further analysis, VMP was shown to have achieved statistically-significant superiority across all efficacy measures compared to MP alone. Patients still on treatment in the control arm were allowed to cross over to the VMP regimen.
The study encompassed 151 centres in 22 countries across Europe, North and South America, and Asia, and is the basis for the approval applications currently under consideration by health regulatory agencies in the European Union, United States and Canada, as well as planned submissions in most other countries by the end of 2008.
About VELCADE(R)
VELCADE(R) is the first proteasome inhibitor to receive worldwide regulatory approval for the treatment of MM. In 2005, VELCADE was approved in the European Union after first relapse and now is indicated as monotherapy for use in patients with progressive MM who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation. Clinical trials are now underway to investigate the potential of VELCADE in earlier settings and in combination with other anti-cancer drugs to enhance treatment effects or reverse resistance(i).
VELCADE has a predictable safety profile and a favourable benefit-risk ratio. The most common side effects reported with VELCADE include fatigue, gastrointestinal adverse events, transient thrombocytopenia and neuropathy, which is reversible in the majority of patients.
VELCADE is the market leader in treating relapsed multiple myeloma with over 100,000 patients treated worldwide. VELCADE is being co-developed by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) and Millennium Pharmaceuticals, Inc. Millennium is responsible for commercialisation of VELCADE in the U.S. For a limited period of time, Millennium and Ortho Biotech Inc. will co-promote VELCADE in the U.S. Janssen-Cilag companies are responsible for commercialisation in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialisation in Japan.
Notes to Editors:
- Multiple myeloma (MM) is the second most common blood cancer, representing approximately one percent of all cancers and two percent of all cancer deaths(ii).
- In 2002, there were approximately 85,700 cases of MM worldwide(iii).
- Only 30 percent of MM patients survive longer than five years(iv), with more than 18,000 people in the European Union dying each year from the disease(v).
- M-protein is an antibody found in unusually large amounts in the blood or urine of people with MM and other types of plasma cell tumours. It is also called monoclonal protein(vi).
- P-value is a statistics term. It is the measure of probability that a difference between groups during an experiment happened by chance. For example, a p-value of .01 (p = .01) means there is a 1 in 100 chance the result occurred by chance. The lower the p-value, the more likely it is that the difference between groups was caused by treatment(vii).
(i) Chiechanover A, Schwartz AL. The ubiquitin system: pathogenesis of human diseases and drug targeting. Biochim Biophys Acta 2004;1695(1-3):3-17.
(ii) www.multiplemyeloma.org.
(iii) GLOBOCAN 2002, www-dep.iarc.fr.
(iv) Brenner H. Lancet 2002; 360:1131-1135.
(v) GLOBOCAN 2002, www-dep.iarc.fr.
(vi) National Cancer Institute. NCI Dictionary of Cancer Terms: M-protein. http://www.cancer.gov/dictionary. Accessed 10 June 2008.
(vii) National Cancer Institute. NCI Dictionary of Cancer Terms: P-value. http://www.cancer.gov/dictionary. Accessed 20 November 2007.
For more information, please contact: Satu Kaarina Glawe, Communications EMEA, BIO, phone +49-173-746-7682
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