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
- 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:
- 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.
(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.
cancer/dictionary. Accessed 10 June 2008.
(vii) National Cancer Institute. NCI Dictionary of Cancer Terms: P-value.
cancer/dictionary. Accessed 20 November 2007.
Janssen-Cilag International NV
www.janssen-cilag
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