INVESTORS & MEDIA
News Release
ZALTRAP® (ziv-aflibercept) Receives CHMP Positive Opinion in the European Union for Previously Treated Metastatic Colorectal Cancer
"We are pleased that CHMP has supported our ZALTRAP application. This brings us one step closer to bringing this novel treatment with a proven survival benefit to colorectal cancer patients in
"It is gratifying to see the years of effort that went into designing and developing the angiogenesis inhibitor ZALTRAP translate into a clinical benefit for patients with metastatic colorectal cancer that has progressed on prior therapy," said
ZALTRAP received approval from the
About the VELOUR Phase 3 Study
The VELOUR trial was a Phase 3 multinational, randomized, double-blind trial comparing FOLFIRI in combination with either ZALTRAP or placebo in the treatment of patients with mCRC. The study randomized 1,226 patients with mCRC who previously had been treated with an oxaliplatin-containing regimen. Twenty-eight percent of patients in the study received prior bevacizumab therapy. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, overall response rate, and safety.
The VELOUR trial showed that in patients previously treated with an oxaliplatin-containing regimen, adding ZALTRAP to FOLFIRI significantly improved median survival from 12.06 months to 13.50 months (HR=0.817 [95% CI 0.714 to 0.935]; p=0.0032), an 18 percent relative risk reduction. A significant improvement in progression-free survival from 4.67 months to 6.90 months (HR=0.758 [95% CI 0.661 to 0.869]; p=0.00007), a 24 percent relative risk reduction, was also observed. The overall response rate in the ZALTRAP plus FOLFIRI arm was 19.8% vs. 11.1% for FOLFIRI (p=0.0001).
The most common adverse reactions (all grades, greater than or equal to 20% incidence) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were leucopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache. The most common Grade 3-4 adverse reactions (greater than or equal to 5%) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leucopenia, stomatitis, fatigue, proteinuria, and asthenia.
About ZALTRAP® (ziv-aflibercept) Injection for Intravenous Infusion
ZALTRAP is recombinant fusion protein that binds the angiogenic proteins Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B and placental growth factor (PIGF). VEGF-A is one of the mediators contributing to angiogenesis. VEGF-B and PlGF, related growth factors in the VEGF family, may contribute to tumor angiogenesis as well. In the U.S., ZALTRAP is a registered trademark of
Important Safety Information for ZALTRAP from the U.S. Prescribing Information
WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING |
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Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in the patients who have received ZALTRAP in combination with FOLFIRI. Monitor patients for signs and symptoms of GI bleeding and other severe bleeding. Do not administer ZALTRAP to patients with severe hemorrhage. |
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GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP. Discontinue ZALTRAP therapy in patients who experience GI perforation. |
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Severe compromised wound healing can occur in patients receiving ZALTRAP/FOLFIRI. Discontinue ZALTRAP in patients with compromised wound healing. Suspend ZALTRAP for at least 4 weeks prior to elective surgery, and do not resume ZALTRAP for at least 4 weeks following major surgery and until the surgical wound is fully healed. |
WARNINGS AND PRECAUTIONS
- Patients treated with ZALTRAP® have an increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
- Monitor patients for signs and symptoms of bleeding.
- Do not initiate ZALTRAP to patients with severe hemorrhage.
- Discontinue ZALTRAP in patients who develop severe hemorrhage.
- GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP.
- Monitor patients for signs and symptoms of GI perforation.
- Discontinue ZALTRAP in patients who experience GI perforation.
- Discontinue ZALTRAP in patients with compromised wound healing.
- Suspend ZALTRAP for at least 4 weeks prior to elective surgery
- Do not initiate/resume ZALTRAP until at least 4 weeks after surgery and surgical wound is fully healed.
- Fistula formation involving GI and non-GI sites occurs at a higher incidence in patients treated with ZALTRAP. Discontinue ZALTRAP therapy in patients who develop fistula.
- An increased risk of Grade 3-4 hypertension has been observed in patients receiving ZALTRAP.
- Monitor blood pressure every two weeks or more frequently and treat with appropriate anti-hypertensive therapy during treatment with ZALTRAP.
- Temporarily suspend ZALTRAP until hypertension is controlled, and reduce ZALTRAP dose to 2 mg/kg for subsequent cycles.
- Discontinue ZALTRAP in patients with hypertensive crisis.
- Arterial thromboembolic events (ATE), including transient ischemic attack, cerebrovascular accident, and angina pectoris, occurred more frequently in patients who have received ZALTRAP. Discontinue ZALTRAP in patients who experience an ATE.
- Severe proteinuria, nephrotic syndrome, and thrombotic microangiopathy (TMA) occurred more frequently in patients treated with ZALTRAP.
- Suspend ZALTRAP when proteinuria greater than or equal to 2 grams/24 hours and resume ZALTRAP when proteinuria < 2 grams/24 hours.
- If recurrent, suspend until proteinuria < 2 grams/24hours and then reduce ZALTRAP dose to 2 mg/kg.
- Discontinue ZALTRAP if nephrotic syndrome or TMA develops.
- A higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection) occurred in patients receiving ZALTRAP.
- Delay administration of ZALTRAP/FOLFIRI until neutrophil count is greater than or equal to1.5 x 109/L.
- Incidence of severe diarrhea and dehydration is increased in patients treated with ZALTRAP/FOLFIRI.
- The incidence of diarrhea is increased in patients greater than or equal to 65 years of age. Monitor closely.
- Discontinue ZALTRAP in patients who develop reversible posterior leukoencephalopathy syndrome.
ADVERSE REACTIONS
- The most common adverse reactions (all grades, greater than or equal to 20% incidence) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
- The most common Grade 3-4 adverse reactions (greater than or equal to 5%) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.
- Infections occurred at a higher frequency in patients receiving ZALTRAP/FOLFIRI (46%, all grades; 12%, Grade 3-4) than in patients receiving placebo/FOLFIRI (33%, all grades; 7%, Grade 3-4), including urinary tract infection, nasopharyngitis, upper respiratory tract infection, pneumonia, catheter site infection, and tooth infection.
- In patients with mCRC, venous thromboembolic events (VTE), consisting primarily of deep venous thrombosis and pulmonary embolism, occurred in 9% of patients treated with ZALTRAP/FOLFIRI and 7% of patients treated with placebo/FOLFIRI.
Please click here for full U.S. Prescribing Information for ZALTRAP (ziv-aflibercept) Injection for Intravenous Infusion, including Boxed WARNING, and visit: www.ZALTRAP.com
About Colorectal Cancer
Worldwide, colorectal cancer is the third most commonly diagnosed cancer in males and the second most in females, with more than 1.2 million new cases diagnosed in 2008. One of the deadliest cancers, colorectal cancer was responsible for more than 600,000 deaths globally in 2008 alone. According to the
About Sanofi Oncology
Based in
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Regeneron is a fully integrated biopharmaceutical company that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets three products in
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