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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.

 How is administered?

Neovastat is administered orally and can be used alone or in combination with other therapies.

Why use it in Multiple Myeloma?

As angiogenesis promotion is involved in the pathophysiology of Multiple Myeloma, its inhibition may represent an innovative approach in the treatment of this disease.

How does it work ?

Unique multiple mechanisms of action

Studies have presented evidence supporting the anti-angiogenic activity of Neovastat and its effects on multiple levels of the angiogenic cascade.

  • Blocking VEGF binding. 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.
  • Inhibiting MMPís. 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 invasion (metastasis)..
  • Induction of 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.  
  • Increase in 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.

 Anti-tumor and Anti-metastatic properties

 Studies by independent laboratories have demonstrated Neovastat' s antitumor and Anti metastatic properties, both alone and in combination with chemotherapy.

  • Anti-metastatic properties: 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.
  • Anti-tumor properties: 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.

 Excellent safety and tolerability profile with signs of efficacy

 Neovastat has 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. Clinical experience includes:

  • Increased 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.
  • Survival 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).

 In summary!

Its multiple 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.

 The figure below describes the process of angiogenesis and shows the actions of Neovastat

 

 

 
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