What is Neovestat?
Neovastat is a
naturally occurring anti-angiogenic compound, extracted from cartilage, with
multiple anti-angiogenic mechanisms of action that provide broad therapeutic
potential for a number of diseases. It is currently in international Phase III
trials for renal cell carcinoma and non-small-cell lung cancer.
administered orally and can be used alone or in combination with other
Why use it in Multiple Myeloma?
promotion is involved in the pathophysiology of Multiple Myeloma, its
inhibition may represent an innovative approach in the treatment of this
How does it work
mechanisms of action
presented evidence supporting the anti-angiogenic activity of Neovastat and its
effects on multiple levels of the angiogenic cascade.
Studies reveal that Neovastat contains a component that specifically prevents
the binding of VEGF (Vascular Endothelial Growth Factor) to its receptors. The
prevention of the binding of VEGF to its receptors is an important factor in
the prevention and containment of tumor growth. Tumors secrete VEGF, which
binds to specific receptors resulting in the sprouting of capillaries from the
blood vessel toward the tumors. Blocking the receptors where VEGF binds on the
surface of endothelial cells disables the capacity of most tumors to stimulate
the formation of blood vessels and thus deprives the tumor of the necessary
nutrients to grow.
Results of studies reveal strong inhibition of gelatinolytic and elastinolytic
activities for MMP-2, MMP-9, and MMP-12. The MMP's are often over expressed in
tumors and play an important role in the degradation of the matrix that
surrounds the cell (extracellular matrix), which allows tumor growth and
endothelial cell specific apoptosis.
Induction of apoptosis (programmed cell death) is an additional Anti
angiogenic activity found in Neovastat. The induction of endothelial cell
apoptosis by Neovastat may thus prevent the formation of new blood vessels.
the level and the activity of tissue-type plasminogen activator (t-PA).
Data from an experimental study (glioblastoma) shows that Neovastat is capable
of increasing the level and activity of t-PA from endothelial cells present
within the tumor. The t-PA may induce the disintegration of blood vessels
present inside the tumor.
and Anti-metastatic properties
independent laboratories have demonstrated Neovastat' s antitumor and Anti
metastatic properties, both alone and in combination with chemotherapy.
Results of animal studies of the effect of Neovastat on lung metastasis show a
significant decrease in the number of lung nodules when Neovastat was used
alone or in combination with Cisplatin. Neovastat was also shown to decrease
bone metastasis in mice.
Studies performed with a mouse model of breast cancer (DA3 adenocarcinoma)
demonstrates that oral administration of Neovastat for 54 days inhibits the
progression of tumor volume by 60% compared to the control group. In
experimental glioblastoma implanted in the brain, Neovastat was shown to
significantly increase mice survival.
safety and tolerability profile with signs of efficacy
shown a consistently excellent safety and tolerability profile in clinical
studies involving more than 850 patients. Some patients have been receiving
treatment for almost four years.
patient survival time in patients with non-small-cell lung cancer (NSCLC):
A Phase I/II trial in patients with NSCLC that were refractory to standard
therapies (Stages III and IV) showed encouraging efficacy results at optimal
doses. In a retrospective analysis of patient survival time, it has been
evidenced that patients treated with the higher dose (240 ml/day) experienced
a median survival time of up to 47% longer than patients who received lower
doses of Neovastat.
benefit in patients with renal cell carcinoma (RCC):
Among the patients included in a Phase II open-label trial, a prospective
survival analysis was performed in 22 patients with metastatic RCC refractory
to standard therapies or for whom no treatment was available. Patients were
treated with 60 ml/day (8 patients) or 240 ml/day (14 patients). Median
survival time in patients receiving 240 ml/day has been found significantly
longer as compared to the median survival time in patients receiving 60 ml/day
(16.3 vs 7.1 months; p=0.01).
mechanisms of action (anti-VEGF activity and inhibition of MMP-2, MMP-9 and
MMP-12), its oral administration and good safety profile after short or long
term administration, are characteristics that make Neovastat an treatment option
for Multiple Myeloma.
below describes the process of angiogenesis and shows the actions of Neovastat