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Clinical Updates — Clinical Updates

An Update on Conbercept as Another Potential Anti-VEGF Agent for US Retina Specialists

In late 2013, Chengdu Kanghong Pharmaceutical Group gained China Food and Drug Administration (CFDA) approval of conbercept for the treatment of exudative macular degeneration.

Conbercept is a recombinant fusion protein composed of the second Ig domain of VEGFR1 and the third and fourth Ig domains of VEGFR2 to the constant region (Fc) of human IgG1. To provide members with an update on this agent, we recently caught up with Xiaoxin Li, MD, PhD, of the People's Eye Center of Peking University, Beijing, China,  and Peter K. Kaiser, of the Cole Eye Institute, Cleveland, Ohio, for an update on the progress with this therapeutic agent.

Tom Albini: Dr. Li, what is the unmet need that conbercept fills?

Xiaoxin Li: Before the advent of conbercept, there were only 3 VEGF inhibitors on the market developed specifically for the treatment of age-related macular degeneration (AMD) and other macular diseases:

• Pegaptanib
• Ranibizumab
• Aflibercept

Additionally,  bevacizumab was available for off-label use.

Ranibizumab started a new era of anti-VEGF therapy, but achieving its greatest efficacy requires monthly injections, which imposes a burden on patients due to frequent visits.

This resulted in an increasing need for a drug requiring less frequent injections but with comparable efficacy (ie, bimonthly aflibercept, which yields similar effects to ranibizumab). Conbercept is the newcomer in this treatment family and has demonstrated promising properties and excellent efficacy with potential trimonthly administration. Drugs with multiple targets such as aflibercept and conbercept show greater potential in dealing with VEGF-related ocular diseases, in contrast with single-target ranibizumab and bevacizumab.

Tom Albini: Dr. Kaiser, where do you think this drug fits in to the spectrum anti-VEGF currently available globally?

Peter Kaiser: There is preclinical evidence that conbercept may last longer than aflibercept with similar efficacy. This remains to be proven, of course, so worldwide studies are being considered for the drug

Tom Albini: Dr. Li, what are the strongest clinical data available about the efficacy of this drug?
 

Xiaoxin Li: The most relevant data have been found in phase 3 of the Phoenix Study, a 52-week investigation of conbercept. In the study, 1 group received conbercept 0.5 mg/eye monthly for 3 months followed by 0.5 mg/eye every 3 months (normal treatment) compared to a delayed treatment group which received sham injections for 3 months followed by 0.5 mg/eye monthly for 3 months followed by 0.5 mg/eye every 3 months (n = 124, completed).

The purpose of the study was to determine the efficacy of novel dosing regimen as 3+q3m, and it demonstrated some positive results. After the 3-month loading period, the normal treatment group witnessed a statistical 9.2-letter improvement in best-corrected visual acuity (BCVA) and 79.2 µm reduction in central retinal thickness (CRT), while BCVA and CRT in the delayed treatment arm remained unchanged from baseline.

At the conclusion of the trial, the normal treatment group had a 9.9-letter improvement, while the delayed treatment group achieved an 8.8-letter improvement, with statistical significance in both compared with baseline. At month 12, reduction in CRT in the normal and delayed treatment groups were 90.9 µm and 135.4 µm, respectively.

Tom Albini: Dr. Kaiser, how do you interpret the data from the Phoenix study?
 

Peter Kaiser: The study showed that conbercept can improve vision and reduce retinal thickness over a longer period of time than some our current anti-VEGF agents

Tom Albini: Dr. Li, what complications and adverse events have been seen?
 

Xiaoxin Li: There were no drug-related abnormalities in the laboratory analyses, electrocardiogram, abdominal ultrasound, and chest X-ray, and there were also no drug-related serious adverse events (AEs) or specific cardiovascular (Antiplatelet Trialists’ Collaboration; APTC) events. The most common AEs were hemorrhage at the injection site, conjunctival congestion, and elevated intraocular pressure (IOP). Drug-related immunogenicity did not develop in subjects in any of the trial groups.

Tom Albini: Dr. Li, how much does the drug cost and where is it available for use?
 

Xiaoxin Li: For now, conbercept is only commercialized in China, where the price for conbercept is nearly 1100 USD per vial. Chengdu Kanghong is actively applying investigational new drug in US and other Asia countries. 
 

Tom Albini: Dr. Kaiser, do you think conbercept has potential in the US?

Peter Kaiser: The potential would be if the drug enters the US market at a much lower price point than the current FDA-approved drugs, aflibercept and ranibizumab. It still will be more expensive than bevacizumab, but if it works similarly or better than aflibercept and is much cheaper, this could be a potent competitor in the market. Moreover, it may bring the cost of drugs down, which would be beneficial in the at-risk insurance environment we face in the future.

Tom Albini: Thank you both for sharing this information. We will be sure to track the progress of this agent, and it seems likely we will be seeing it, or some form of it, in the US in the future.

 Published September 2014