Novel anti-VEGF agent approved in China may reduce injection frequency

Conbercept is an anti-vascular endothelial growth factor (VEGF) drug approved for the treatment of wet age-related macular degeneration in China. Compared with agents used in the United States, it has a higher binding affinity, lower VEGF dissociation rate, and longer clearance time.

Reviewed by Peter K. Kaiser, MD

Conbercept-an anti-vascular endothelial growth factor (VEGF) drug approved for the treatment of wet age-related macular degeneration (AMD) in China-appears to have the same safety and efficacy profile of the anti-VEGF medications available in the United States, but may allow for reduced dosing frequency, according to Peter K. Kaiser, MD.

“The Chinese company [Kanghong Biotech, Chengdu, China] that developed conbercept is now in discussion with the FDA and with the European Medicines Agency to bring this product to other countries,” said Dr. Kaiser, Chaney Family Endowed Chair in Ophthalmology Research and Professor of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland.

“Hopefully, it will become an additional option to use in the future for treating wet AMD,” he added.

How it compares, differs

Conbercept is similar to aflibercept in that it is a recombinant fusion protein of key extracellular domains from human VEGF receptors 1 and 2 and IgG Fc produced in a Chinese hamster ovarian cell line. However, conbercept also contains the fourth domain of the VEGF receptor 2, which results in several differences. Compared with aflibercept, conbercept is slightly larger, has a lower VEGF dissociation rate and higher binding affinity, exhibits decreased adhesion to the extracellular matrix, and has a lower isoelectric point that results in a longer clearance time.

“Conbercept has an intravitreal half-life of about 1 week,” Dr. Kaiser said.

In addition, conbercept blocks all VEGF-A isoforms as well as VEGF-B, VEGF-C, and placental growth factor. Reviewing clinical studies investigating conbercept for the treatment of wet AMD in China, Dr. Kaiser said the first phase II trial compared two doses of the anti-VEGF agent, 0.5 and 2.0 mg, in patients with any treatment-naïve lesion. Subjects received 3 monthly injections and were evaluated at the primary endpoint at month 3. Thereafter, treatment was given as needed with a final visit at 1 year.

Both the 0.5 and 2.0 mg doses were associated with improvements from baseline vision. At month 12, the mean improvement was +16.4 letters in eyes treated with the 2.0 mg dose (mean 6.8 injections) and +15.1 letters for the 0.5 mg group (mean 5.2 injections).

A second phase II study included a larger patient population and evaluated the same two conbercept doses but compared monthly and as needed treatment with each dose. Again, there were no differences in BCVA improvement between doses, and so the 0.5 mg dose was investigated in the phase III study.

Early findings from the phase III trial

The phase III trial had a sham control group and a primary endpoint at month 3, although patients were followed for safety until 12 months. Patients randomly assigned to conbercept received a loading dose with 3 injections at monthly intervals and then were treated every 3 months thereafter. The control group received 3 sham injections and then was crossed over to conbercept at month 3, beginning with the loading dose and then switching to quarterly injections.

At the primary endpoint assessment at month 3, patients treated with conbercept had a mean BCVA gain of +9.2 letters and the central retinal thickness (CRT) was reduced by a mean of 79.2 µm. BCVA and CRT were unchanged in the control group.
At month 12, BCVA was improved from baseline by a mean of +9.9 letters in the group randomized initially to conbercept and by +8.8 letters in the controls who had crossed over to conbercept at month 3. CRT was reduced by an average of 90.9 and 135.4 µm in the two groups, respectively.

At month 12, the serious adverse event rate was 7.4%, which is consistent with that observed with other antiVEGF agents, Dr. Kaiser said. One patient experienced an arterial thromboembolic event. Overall, most adverse events were related to the injection, mild, and transient.

Disclosures:

Peter K. Kaiser, MD
E: pkkaiser@me.com
Dr. Kaiser is a consultant to Changdu Kanghong Biotech and to other companies marketing and developing anti-VEGF treatments for wet AMD, including Alcon Laboratories, Bayer, Genentech, Novartis, Neurotech, and Ohr Pharmaceuticals, and Regeneron.