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Early data on CAT-152 suggest role in trabeculectomy
Trials have not identified any adverse events or problems not already expected following glaucoma filtering surgery.
NORWICH, England — Early clinical trial data on CAT-152 indicate the drug could prevent postoperative wound scarring following trabeculectomy, according to one of the drug’s investigators. The monoclonal antibody may be a less damaging alternative to 5-fluorouracil or mitomycin-C, said David C. Broadway, MD, FRCOphth.
CAT-152 (Cambridge Antibody Technology) recently completed a phase 2 trial evaluating the drug’s safety and tolerability in a combined cataract and trabeculectomy procedure. Follow-up in the trial has been extended an additional 2 years. Another trial evaluating the drug in a trabeculectomy procedure alone has also recently been initiated.
Dr. Broadway stressed that the data is only in early stages, but he said it is encouraging.
“It is not going to transform glaucoma surgery overnight,” he said. “We are at a relatively early stage. We know it is relatively safe and the tolerability is good. But we have to work on how efficacious it is and how much dosing is required for the desired effect.”
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He said the investigators’ clinical impression is that the drug helps produce more stable blebs. However, the investigators have not fully analyzed all the bleb photographs, so he said this is anecdotal.
“But we do get the impression we are producing blebs that are more physiological,” he said. “They are not thin, horrible, cystic blebs that can develop following the use of other antiproliferative agents. They appear to be more diffuse and have normal conjunctival thickness. They are nicely smooth posterior, up under the upper eye lids and produce less risks of problems like leaking and endophthalmitis. Probably more comfort, too.”
Dr. Broadway stressed that further analysis is needed to verify this impression.
“That is something we are looking at pretty closely in the second trial; the actual bleb type. The patients are having photographs of their blebs at every visit,” he said.
CAT-152
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CAT-152 is a human monoclonal antibody that neutralizes transforming growth factor beta 2 (TGFß2), which, Dr. Broadway said, has been shown in animal and human studies to be one of the most potent factors known to stimulate wound healing in both the skin and the eye.
“The theory is, therefore, that if you are knocking out the most potent stimulators of wound healing then the wounds would heal less, which is what we want after a trabeculectomy,” he said.
He added that CAT-152 is “definitely” safer than mitomycin, but is probably not as potent. He said one issue they hope to address in the trials is whether it will be sufficiently potent.
“Mitomycin is more like putting an atom bomb on the eye rather than something with a bit of finesse,” he said, explaining that mitomycin basically knocks out all dividing cells and completely kills fibroblasts.
“CAT-152 doesn’t act on the cell. It’s actually mopping up the TGFß2, which is stimulating the cells. It is not killing cells, which is why we are very hopeful that our sort of anecdotal assumption that we are producing nicer blebs has some clinical or scientific basis,” he said.
Combined procedure trial
The phase 2 clinical trial evaluated the drug in a combined phacoemulsification and trabeculectomy procedure. The trial has completed 1 year follow-up, and patient follow-up has been extended an additional 2 years.
Dr. Broadway explained they chose to evaluate the drug initially in a combined procedure because of the additional risk of trabeculectomy failure in such cases.
“Phaco trabeculectomies don’t seem to do as well as trabeculectomy alone,” he said.
The randomized, double-masked study included 56 patients divided into two groups: 20 patients given placebo and 36 patients treated with CAT-152. Patients were injected with 100 µL of CAT-152 or placebo immediately before and upon completion of a routine combined phaco and trabeculectomy procedure. Additional injections were given at 1 day and 1 week postop.
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Mr. Broadway said patients had better IOP control in the CAT-152 treatment group after 1 year, and fewer patients had to resume topical IOP-lowering drugs (CAT-152, 11% vs. placebo, 20%).
According to a poster presented earlier this year at the Association for Research in Vision and Ophthalmology meeting, IOP was significantly lower in the CAT-152 treatment group, with patients’ IOPs an average 2.3 mm Hg lower than the placebo group.
“The difference isn’t enormous. It’s not an agent as potent as mitomycin-C. But it does seem at least to be on a par with 5-FU,” he said.
All patients treated with CAT-152 achieved IOPs less than 22 mm Hg. This compared to 85% of patients in the placebo group.
According to Mr. Broadway, the drug has not caused any problems or adverse events that would not be expected following a standard glaucoma filtering procedure.
“The same problems in the early postoperative period do seem to occur. I can’t reveal all the full details, but in the study there were actually less adverse effects in the treatment group compared to the placebo group. So there were no additional adverse effects from it,” he said.
“We saw the normal things you would expect after a trabeculectomy. Some patients had flat anterior chambers in the early postoperative period, the odd hyphema and a bit of discomfort following the operation — reasonably minor things, really.”
Additional study
Enrollment for another trial of CAT-152 involving 300 to 350 patients has been initiated and will evaluate the drug’s effect in trabeculectomy alone. Patients in the study will initially be followed for 1 year, but Mr. Broadway said he hopes the trial will be extended beyond that.
For your information:
- David C. Broadway, MD, FRCOphth, can be reached at Norfolk & Norwich University Hospital, Colney Lane, Norwich, NR4 7UZ, England; (44) 1603-288-373; fax: (44) 1603-288-261; e-mail: davidbroadway@norfolk-norwich.thenhs.com. Mr. Broadway has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Cambridge Antibody Technology, makers of CAT-152, can be reached at The Milstein Building, Granta Park, Cambridge CB1 6GH, United Kingdom; (44) 1223-471-471; fax: (44) 1223-471-472; Web site: www.cambridgeantibody.com.