In mid-June, NeoVista announced the initiation of its CABERNET (Cnv secondary to AMD treated with BEta RadiatioN Epiretinal Therapy) clinical trial for the treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD).
The CABERNET study will employ the company’s Epi-Rad90 ophthalmic system to deliver Strontium 90 directly to the retina (using an outpatient partial vitrectomy), along with an injection of an anti-VEGF agent (Lucentis) at the time of surgery, followed by a second injection of Lucentis 30 days thereafter. The control arm of the study will utilize Lucentis injections alone.
The company noted that it was following the PIER regimen for Lucentis in the control arm, which represents 3 initial monthly injections and then quarterly after that. There is also a rescue plan in place for those patients who begin reverting back to worsening VA. They chose to follow this path, as PIER is the only trial that treated all types of CNV, thus providing them the broadest possible label.
The CABERNET clinical trial will include 30 clinical sites, with 20 in the U.S., and 10 spread across Europe, Israel, and South America. The study will involve 495 patients followed for 2 years; 330 receiving the 24 Gy dosage of Strontium-90 plus Lucentis, and 165 receiving only the Lucentis injections.
In addition to the information about the start of the CABERNET study, the company also sent along information updating its previously reported results of both its Radiation Only feasability study, now out to 18 months, with vision holding at +6.4 letters (as shown below in Graph 1), and 9 month data on its Concomitant Study, which utilized two injections of Avastin along with a treatment of Strontium-90. These results are shown in Graph 2 below.
The CABERNET study will employ the company’s Epi-Rad90 ophthalmic system to deliver Strontium 90 directly to the retina (using an outpatient partial vitrectomy), along with an injection of an anti-VEGF agent (Lucentis) at the time of surgery, followed by a second injection of Lucentis 30 days thereafter. The control arm of the study will utilize Lucentis injections alone.
The company noted that it was following the PIER regimen for Lucentis in the control arm, which represents 3 initial monthly injections and then quarterly after that. There is also a rescue plan in place for those patients who begin reverting back to worsening VA. They chose to follow this path, as PIER is the only trial that treated all types of CNV, thus providing them the broadest possible label.
The CABERNET clinical trial will include 30 clinical sites, with 20 in the U.S., and 10 spread across Europe, Israel, and South America. The study will involve 495 patients followed for 2 years; 330 receiving the 24 Gy dosage of Strontium-90 plus Lucentis, and 165 receiving only the Lucentis injections.
In addition to the information about the start of the CABERNET study, the company also sent along information updating its previously reported results of both its Radiation Only feasability study, now out to 18 months, with vision holding at +6.4 letters (as shown below in Graph 1), and 9 month data on its Concomitant Study, which utilized two injections of Avastin along with a treatment of Strontium-90. These results are shown in Graph 2 below.
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Graph 1.
Graph 2.(See my February 14, 2007 report for the full initial story.)
These updated results were reported by the company at the recent (May 30 – June 2nd) Macular Society Meeting held in London. The nine-month Concomitant Study results show equivalent results to the ANCHOR Study, which applied monthly doses of Lucentis to patients over a 2 year period.
As a result of this updated data and the start of the CABERNET study, the following key questions were posed to the company:
1) The Epi-Rad90 arm of the feasability study appears to be showing increased VA, especially in months 9 - 12. Although the results decreased again (according to your reports) out to month 18. Is there any thought of performing a second treatment of radiation, or adding an injection of anti-VEGF agent at the two-year period?
Given that radiation alone is likely not to have the same efficacy as concomitant treatment over a 2-year period, we must wait to learn the 2 year results of both arms for proper comparison. As for the possibility of a second radiation treatment, this is an opportunity that will require much investigation. At this stage of our existence, we are not able to investigate all opportunities presented us and realize that concluding the CABERNET trail must remain our first priority.
2) The Concomitant Study arm results appear to be leveling off after 6 months. Would another shot of Avastin at, say 9 months, be expected to show further improvements?
Time will tell. We will likely see an increase in cataract formation in the treated group in the first year post-op. Post-cataract procedure exams showed an increase in VA again between 9 and 12 months in the Radiation Only Study. As you know, cataract formation is a common occurrence in patients undergoing vitrectomy. Our procedure has shown a much lower incidence of cataract procedure than standard Vitrectomy outcomes. We believe this is due to the use of a partial versus complete Vitrectomy. Another point to make; many of those eligible for our procedure will have likely already had cataract surgery due to natural change.
3) Is OCT inspection of the retina part of the followup examinations – similar to the PRONTO Study?
We are utilizing both OCT and FA (fluorescein angiogram) in CABERNET via assigned Reading Centers. In our feasibility studies, OCT and FA were utilized. For CABERNET rescue requirements, one component of judging whether or not to re-inject will be the OCT image analysis.
(A writeup of the PRONTO Study is shown in a separate report – see Two-Year Results of the PRONTO Study on this web site.)
For Information Only:
The MARINA study enrolled patients with occult and minimally classic choroidal neovascularization (CNV), the form of CNV found in most patients with wet AMD, while the ANCHOR study enrolled patients with predominantly classic CNV.
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab (Lucentis) In the treatment of Neovascular AMD) was a Phase III randomized, multi-center, double-masked, sham-controlled study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 1:1:1 to receive intravitreal ranibizumab injections (0.3 mg or 0.5 mg) or a control regimen once a month for two years. The control regimen consisted of a sham injection, meaning the treating physician prepared and anesthetized the patient’s eye but did not perform an injection.
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) was a Phase III randomized, multi-center, double-masked, active-treatment controlled study comparing two different doses of Lucentis to verteporfin (Visudyne) photodynamic therapy (PDT) in 423 patients with predominantly classic wet AMD in the United States, Europe and Australia. Patients were randomized 1:1:1 to receive intravitreal ranibizumab injections (0.3 mg or 0.5 mg) once a month or PDT every three months for two years.
These updated results were reported by the company at the recent (May 30 – June 2nd) Macular Society Meeting held in London. The nine-month Concomitant Study results show equivalent results to the ANCHOR Study, which applied monthly doses of Lucentis to patients over a 2 year period.
As a result of this updated data and the start of the CABERNET study, the following key questions were posed to the company:
1) The Epi-Rad90 arm of the feasability study appears to be showing increased VA, especially in months 9 - 12. Although the results decreased again (according to your reports) out to month 18. Is there any thought of performing a second treatment of radiation, or adding an injection of anti-VEGF agent at the two-year period?
Given that radiation alone is likely not to have the same efficacy as concomitant treatment over a 2-year period, we must wait to learn the 2 year results of both arms for proper comparison. As for the possibility of a second radiation treatment, this is an opportunity that will require much investigation. At this stage of our existence, we are not able to investigate all opportunities presented us and realize that concluding the CABERNET trail must remain our first priority.
2) The Concomitant Study arm results appear to be leveling off after 6 months. Would another shot of Avastin at, say 9 months, be expected to show further improvements?
Time will tell. We will likely see an increase in cataract formation in the treated group in the first year post-op. Post-cataract procedure exams showed an increase in VA again between 9 and 12 months in the Radiation Only Study. As you know, cataract formation is a common occurrence in patients undergoing vitrectomy. Our procedure has shown a much lower incidence of cataract procedure than standard Vitrectomy outcomes. We believe this is due to the use of a partial versus complete Vitrectomy. Another point to make; many of those eligible for our procedure will have likely already had cataract surgery due to natural change.
3) Is OCT inspection of the retina part of the followup examinations – similar to the PRONTO Study?
We are utilizing both OCT and FA (fluorescein angiogram) in CABERNET via assigned Reading Centers. In our feasibility studies, OCT and FA were utilized. For CABERNET rescue requirements, one component of judging whether or not to re-inject will be the OCT image analysis.
(A writeup of the PRONTO Study is shown in a separate report – see Two-Year Results of the PRONTO Study on this web site.)
For Information Only:
The MARINA study enrolled patients with occult and minimally classic choroidal neovascularization (CNV), the form of CNV found in most patients with wet AMD, while the ANCHOR study enrolled patients with predominantly classic CNV.
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab (Lucentis) In the treatment of Neovascular AMD) was a Phase III randomized, multi-center, double-masked, sham-controlled study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 1:1:1 to receive intravitreal ranibizumab injections (0.3 mg or 0.5 mg) or a control regimen once a month for two years. The control regimen consisted of a sham injection, meaning the treating physician prepared and anesthetized the patient’s eye but did not perform an injection.
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) was a Phase III randomized, multi-center, double-masked, active-treatment controlled study comparing two different doses of Lucentis to verteporfin (Visudyne) photodynamic therapy (PDT) in 423 patients with predominantly classic wet AMD in the United States, Europe and Australia. Patients were randomized 1:1:1 to receive intravitreal ranibizumab injections (0.3 mg or 0.5 mg) once a month or PDT every three months for two years.
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