MyVisionTest News Archive
Jan 14, 2012
CATT findings support use of Avastin as alternative to Lucentis
For 5 years, patients and clinicians have wrestled with the choice between two drugs for the treatment of neovascular age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF), the cytokine primarily responsible for blood-vessel growth, is inhibited when anti-VEGF drugs are injected repeatedly into the eye, and blindness is prevented in most patients. The majority of treated patients go on to have some improvement in vision.
The two anti-VEGF drugs most commonly used are bevacizumab (Avastin) and ranibizumab (Lucentis), both developed by Genentech. Avastin, a full-length humanized monoclonal antibody, has been approved by the Food and Drug Administration (FDA) for the systemic treatment of certain cancers. Lucentis, an antigen-binding fragment, is a smaller molecule that was specifically developed and approved to treat eye diseases and is derived from the same anti-VEGF mouse monoclonal antibody as Avastin. Both Lucentis and Avastin bind VEGF at the same position; however, they differ in size, affinity for VEGF, speed of clearance from the eye, and cost. Lucentis, the FDA-approved treatment for neovascular AMD, costs approximately $2,000 per dose, whereas Avastin, the off-label treatment, costs approximately $50. This cost difference, along with the perceived clinical similarities between these two drugs, has led to the widespread use of Avastin in the absence of level I evidence.
Martin and colleagues provide such evidence in their findings from the first year of the Comparison of AMD Treatment Trials (CATT), a large, prospective, multicenter, randomized clinical trial comparing Avastin and Lucentis. Despite formidable obstacles, the investigators successfully compared the two drugs and two different dosing regimens: a monthly regimen versus an as-needed regimen (i.e., drug administration only when signs of exudation are present). An OCT-guided as-needed regimen has been shown to result in improved visual acuity, but CATT is the first prospective approach to directly compare a monthly regimen with an as-needed regimen.
Martin et al. found that the monthly use of either Avastin or Lucentis results in the same visual acuity outcome. This finding holds true for the mean visual acuity and the proportion of patients who gain 15 letters (which represents a doubling of the visual acuity), lose 15 letters, or remain stable. Critics will argue that the OCT outcomes suggest differences between these two drugs. Although the OCT retinal thickness measurements favor Lucentis, this difference is not reflected in any of the visual-acuity or angiographic outcomes.
In addition, Martin et al. observed equivalent visual-acuity outcomes with both the monthly and the as-needed regimens of Lucentis. This result is particularly good news for patients. The success of the as-needed regimen in a multicenter clinical trial cannot be overstated, given the intrinsic difficulties associated with the training of investigators to agree on OCT interpretation and retreatment guidelines. Given deficiencies that were reported by the reading center, it is likely that visual acuity and anatomic outcomes would have been even better with improved investigator compliance.
Although the as-needed regimen with Avastin appeared similar to the as-needed regimen with Lucentis, the as-needed Avastin regimen compared less favorably with monthly regimens for either Avastin or Lucentis. One possibility may be that Avastin has a less durable treatment effect in a subgroup of patients and thus more frequent administration may be required. If the frequency of administration were increased, then the outcomes in such patients should approach the outcomes observed with monthly treatments.
Although CATT addresses the question of efficacy, the study was insufficiently powered to identify differences in drug-related adverse events. Although Avastin persists longer than Lucentis in the systemic circulation after an intravitreal injection, Martin et al. observed none of the expected adverse events associated with systemic anti-VEGF therapy. Although more patients receiving Avastin had multiple systemic serious adverse events and hospitalizations than those receiving Lucentis, these events were not associated with organ systems typically identified with systemic anti-VEGF therapy. The results from the second year of CATT and from five other large, ongoing, multicenter comparative clinical trials in Europe should help to clarify whether these adverse events are related to intravitreal anti-VEGF therapy.
The CATT results, together with the totality of global experience, support the use of either Avastin or Lucentis for the treatment of neovascular AMD. An as-needed regimen is an acceptable alternative to a monthly regimen, but strict compliance on the part of both the clinician and the patient is required. Health care providers and payers worldwide will now have to justify the cost of using Lucentis. Regulators in certain countries will be forced to reconsider their policies that make it illegal to use drugs off-label, particularly when so many of their citizens cannot afford Lucentis. The CATT data support the continued global use of intravitreal Avastin as an effective, low-cost alternative to Lucentis.
Read more...
N Engl J Med. 2011 May 19;364(20):1966-7. Epub 2011 Apr 28.
Tags: clinical trial, Lucentis, Avastin, CATT
For 5 years, patients and clinicians have wrestled with the choice between two drugs for the treatment of neovascular age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF), the cytokine primarily responsible for blood-vessel growth, is inhibited when anti-VEGF drugs are injected repeatedly into the eye, and blindness is prevented in most patients. The majority of treated patients go on to have some improvement in vision.The two anti-VEGF drugs most commonly used are bevacizumab (Avastin) and ranibizumab (Lucentis), both developed by Genentech. Avastin, a full-length humanized monoclonal antibody, has been approved by the Food and Drug Administration (FDA) for the systemic treatment of certain cancers. Lucentis, an antigen-binding fragment, is a smaller molecule that was specifically developed and approved to treat eye diseases and is derived from the same anti-VEGF mouse monoclonal antibody as Avastin. Both Lucentis and Avastin bind VEGF at the same position; however, they differ in size, affinity for VEGF, speed of clearance from the eye, and cost. Lucentis, the FDA-approved treatment for neovascular AMD, costs approximately $2,000 per dose, whereas Avastin, the off-label treatment, costs approximately $50. This cost difference, along with the perceived clinical similarities between these two drugs, has led to the widespread use of Avastin in the absence of level I evidence.
Martin et al. found that the monthly use of either Avastin or Lucentis results in the same visual acuity outcome. This finding holds true for the mean visual acuity and the proportion of patients who gain 15 letters (which represents a doubling of the visual acuity), lose 15 letters, or remain stable. Critics will argue that the OCT outcomes suggest differences between these two drugs. Although the OCT retinal thickness measurements favor Lucentis, this difference is not reflected in any of the visual-acuity or angiographic outcomes.
In addition, Martin et al. observed equivalent visual-acuity outcomes with both the monthly and the as-needed regimens of Lucentis. This result is particularly good news for patients. The success of the as-needed regimen in a multicenter clinical trial cannot be overstated, given the intrinsic difficulties associated with the training of investigators to agree on OCT interpretation and retreatment guidelines. Given deficiencies that were reported by the reading center, it is likely that visual acuity and anatomic outcomes would have been even better with improved investigator compliance.
Although the as-needed regimen with Avastin appeared similar to the as-needed regimen with Lucentis, the as-needed Avastin regimen compared less favorably with monthly regimens for either Avastin or Lucentis. One possibility may be that Avastin has a less durable treatment effect in a subgroup of patients and thus more frequent administration may be required. If the frequency of administration were increased, then the outcomes in such patients should approach the outcomes observed with monthly treatments.
Although CATT addresses the question of efficacy, the study was insufficiently powered to identify differences in drug-related adverse events. Although Avastin persists longer than Lucentis in the systemic circulation after an intravitreal injection, Martin et al. observed none of the expected adverse events associated with systemic anti-VEGF therapy. Although more patients receiving Avastin had multiple systemic serious adverse events and hospitalizations than those receiving Lucentis, these events were not associated with organ systems typically identified with systemic anti-VEGF therapy. The results from the second year of CATT and from five other large, ongoing, multicenter comparative clinical trials in Europe should help to clarify whether these adverse events are related to intravitreal anti-VEGF therapy.
The CATT results, together with the totality of global experience, support the use of either Avastin or Lucentis for the treatment of neovascular AMD. An as-needed regimen is an acceptable alternative to a monthly regimen, but strict compliance on the part of both the clinician and the patient is required. Health care providers and payers worldwide will now have to justify the cost of using Lucentis. Regulators in certain countries will be forced to reconsider their policies that make it illegal to use drugs off-label, particularly when so many of their citizens cannot afford Lucentis. The CATT data support the continued global use of intravitreal Avastin as an effective, low-cost alternative to Lucentis.
Read more...
N Engl J Med. 2011 May 19;364(20):1966-7. Epub 2011 Apr 28.
