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Eylea co-formulated with rinucumab provided no more benefit than Eylea alone in wet AMD
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Regeneron Pharmaceuticals announced that Eylea co-formulated with rinucumab provided no more benefit than Eylea alone in treating patients with neovascular age-related macular degeneration.
In the phase 2 CAPELLA study, the combination therapy did not provide improvement in best corrected visual acuity outcomes in patients with neovascular AMD compared with those who received aflibercept alone, according to a press release. At 12-week follow-up, patients in the combination therapy cohort had a 5.8 letter improvement in BCVA, compared with a 7.5 letter improvement in BCVA in patients treated with aflibercept alone.
The combination therapy also did not improve reduction in retinal thickness or resolution of subretinal hyper-reflective material.
“The addition of rinucumab did not improve on the efficacy of aflibercept alone. We are committed to continuing to innovate for patients with serious vision-threatening diseases, and look forward to the results of our ongoing combination studies of aflibercept and nesvacumab, an anti-angiopoietin 2 antibody, for which the preclinical data is more supportive,” George D. Yancopoulos MD, PhD, chief scientific officer of Regeneron and president of Regeneron Laboratories, said in the release.
The ongoing trial included approximately 500 patients with wet AMD. Patients were randomized to receive fixed doses every 4 weeks of aflibercept monotherapy 2 mg, aflibercept 2 mg/rinucumab 1 mg, or aflibercept 2 mg/rinucumab 3 mg.
The cohorts will be evaluated again at 28 weeks and 52 weeks, when the study is completed.
Perspective
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Pravin U. Dugel MD, OSN Retina/Vitreous Board Member
This is a phase 2-drug study that was done with a co-formulation with two different antibodies. One, an anti-VEGF-A antibody, and the other, an anti-PDGF antibody. The co-formulation included a well-known anti-VEGF-A antibody, Eylea (aflibercept, Regeneron), and, in addition, Regeneron’s own anti-PDGF antibody. This was not a bi-specific molecule, these were not two separate types of drugs given at separate times, this was a co-formulation.
I was not surprised at the data. I saw the results of the phase 1 study and they were not as encouraging as I, and they, had hoped they would be. Therefore, the results of the phase 2 study, at least for me, were not surprising.
This is a very different drug than other anti-PDGF drugs currently being tested, namely the Ophthotech Fovista product, and other anti-PDGFs by other companies. This is a different drug altogether. It is different not only in its formulation, as discussed, but also in its target (receptor versus ligand).
It is important to remember that when you put two antibodies together at a very high concentration, there are interactions that can occur that would be different than if these two products were given individually. These interactions may cause some level of effective neutralization and may cause inflammation. Any of those things can happen. We do not know what the actual reason was for this result, but it is important to remember that having a product co-formulated is different than having individual injections or a product that is bi-specific.
There were several things that were interesting to me when I read the results. One, the combination did worse than aflibercept individually. It begs the question: Did the antibody combinations somehow negate each other? We do not know. The other thing that was striking to me was that there was a greater incidence of pain with the co-formulation than with the monotherapy product, although it was still just one injection. Why would patients have pain with the co-formulation? It is certainly not because of multiple injections, as it is still just one injection. Could it be some other mechanism, such as inflammation caused by the co-formulation? We just do not know as yet.
At the end of the day, what we have is the 12-week results of a 52-week study. We still have a lot more data that we need to analyze. I think the trial is very well designed, I think Regeneron is a good company and this is a target that has to be explored, but I think we need to understand that there are several strategies for exploring this target and they are all different.
There is good, scientific rationale for exploring an anti-PDGF strategy in combination with an anti-VEGF-A. Ultimately, our decisions will be made based on data. We, as physician-scientists, must wait for all the data to come out and refrain from extrapolating and jumping to conclusions.
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