LONDON -- Cambridge Antibody Technology (CAT) Group plc has suspended recruitment into its Phase I/IIa trial of 6B1, an anti-transforming growth factor-beta-2 human monoclonal antibody, for the treatment of proliferative vitreoretinopathy (PVR), following what are described as "unusual observations" made postoperatively in three of 11 actively treated patients.
The suspension does not affect a further trial of 6B1 as a treatment to prevent scarring of the eye at the operation site following glaucoma surgery. CAT, based in Melbourn, Cambridgeshire, has one other compound in clinical trials, D2E7, an antitumor necrosis factor alpha antibody for the treatment of rheumatoid arthritis.
PVR can occur following retinal detachment, and is the factor most responsible for failure in surgery undertaken to reattach the retina. The study began in September 1997 at three U.K. centers, and a total of 16 patients have been treated. CEO David Chiswell told BioWorld International observations of patients "have concentrated on the macula [the area of the retina most responsible for vision]. If that is puckered, it is likely to affect sight. But it was noticed that, outside this, on the edge of the photographs, was an area that was paler than it should be in three patients out of 11."
Chiswell said there was no apparent clinical consequence, and the patients had noticed no effect. However, the company decided the observation required further study over time to evaluate its significance. Patients enrolled to date will be followed up, as planned in the protocol, for a year following treatment. At that time a decision will be made on whether to conduct further trials.
In June 1998, CAT received regulatory approval to conduct trials of 6B1 as a treatment to prevent scarring of the eye following surgery for glaucoma. Recruitment to the Phase I/IIa trial is on plan, and expected to finish by early 1999, with full results available in the middle of the year. Chiswell said there have been no adverse events in this study. "The clinicians in the glaucoma study decided the observations [in the PVR study] were not relevant, because of the different mode of administration."
'Modest' Rise In Cash Burn Expected
Excessive activity of the TGF-beta family of cytokines is associated with organ fibrosis and postsurgical scarring. TGF-beta-2 is the isoform believed to be responsible for scarring in and around the eye.
Suspension of the PVR trial is a blow to CAT's strategy of first establishing the principle of using anti-TGF-beta-2 antibodies in acute indications where a single dose or course of treatment may be sufficient. If this principle can be established, the company plans to extend their use to chronic ophthalmic conditions such as age-related macular degeneration and diabetic retinopathy, where fibrosis can lead to permanent blindness.
CAT announced suspension of the trial as it disclosed results for the full year ended Sept. 30 showing a loss for the year of £7 million (US$11.58 million), down from £8.4 million for the previous year. Operating costs rose to £11.2 million from £8.3 million, while revenues were up to £1.4 million from £1.1 million in 1997. Most income came from the second installment of a license fee from Eli Lilly and Co., of Indianapolis.
Chiswell said the increase in expenditure was in line with the company's plan. "We knew costs would be going up as we recruited more staff and started clinical trials," he said. During the year, staff numbers rose from 98 to 139. Recruitment is now leveling out and will stop at 160, Chiswell said.
Cash burn is expected to rise "modestly" in the coming year to an average of £1.5 million per month, leaving CAT with sufficient funds for two years, Chiswell said. The company, which raised £41 million when it went public in March 1997, said it will require additional funding.
Chiswell called the earnings report a "standard health warning," adding the company is "not yet at the stage where we can say to shareholders we won't need to raise any more money." CAT is talking with potential licensees for its platform technology for rapidly isolating fully human monoclonal antibodies using phage display systems. In 18 months, the company said, the number of human antibodies in its libraries has risen from 10 billion to 100 billion. *