The clinical hold was lifted from Seragen Inc.'s Phase II psoriasistrial after no link was found between the company's fusion moleculeand a blood clot experienced by one of the patients. The companyalso said Thursday it saw good results among those patients treatedbefore the trial was stopped.
With the FDA go-ahead Seragen is planning a series of small studiesof the interleukin-2 fusion protein that would be designed to preparefor a Phase III program. A double-blind placebo-controlled study wasstopped in December after 41 patients were treated in the studydesigned to enroll 60. (See BioWorld Today, Dec. 29, 1995, p. 1.)
"We did a broad safety review across all indications and could notfind any hard evidence that linked the blood clotting to the agent,"said Jean Nichols, Seragen's senior vice president. "However, wecouldn't find any other clear explanation for the blood clotting."
The patient who experienced the adverse event has recovered.Nichols pointed out the blood clot was the first serious safety eventseen in more than 400 people who have been treated with the IL-2Fusion Protein.
"We don't feel terminating the study compromised the goals,"Nichols said. "We learned what we needed to about safety andactivity, and we were able to confirm the first open-label study with aPhase II placebo-controlled study."
Of the 41 treated patients, 29 received the drug (27 were evaluable).The mean improvement, as measured by a Psoriasis AssessmentSeverity Index (PASI) score, was 28 percent. Seventeen patients whocompleted all 12 doses of IL-2 Fusion Protein had a 40 percent meanimprovement from baseline. The 12-patient placebo group had mean12 percent improvement.
The 40 percent mean improvement was in line with what was seen inan earlier study. The PASI, a primary endpoint, measures the degreeof body surface affected and the severity of lesions.
Seragen's stock closed unchanged Thursday at $5. It fell 28 percent,to $4.25, the day the trial was stopped.
The IL-2 Fusion Protein, formerly called a fusion toxin molecule, is adiphtheria toxin fragment A-fragment B, genetically fused to humanIL-2 through amino acid 389 on the toxin chain, Nichols said. Theconstruct targets high-affinity IL-2 receptors on activated Tlymphocytes. Once bound, it enters the cell, where fragment A of thetoxin acts to inhibit protein synthesis, thus killing the cell.
Separately the product is being developed for cancer indications withEli Lilly and Co., of Indianapolis. A phase III trial is ongoing incutaneous T cell lymphoma. Seragen has all dermatological rights tothe product.
George Masters, president and CEO of Seragen, said companyofficials are exploring deals with potential partners in dermatologyand he hopes to have a deal in place by late summer/early fall. Hesaid the hold put on the trial slowed those talks, but the ensuingpositive data should put the program right back on track.
Masters said Seragen hopes to start new trials of IL-2 Fusion Proteinby mid-year. The company has cash on hand to get only throughAugust, however, he said. "We're looking at several financingalternatives, which we'll be putting in place in the near future, in amove to shore up our balance sheet." n
-- Jim Shrine
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