By Randall Osborne
Boston Life Sciences Inc. (BLS) said the latest in a series of Phase III trials with Therafectin for rheumatoid arthritis has reaped encouraging results, and the company will file for marketing approval with the FDA in the first quarter of this year.
Therafectin, a carbohydrate compound, was deemed not approvable by the FDA in early 1994. The drug then belonged to Greenwich Pharmaceuticals Inc., of Fort Washington, Pa., with which BLS, of Boston, merged the following year.
Marc Lanser, chief scientific officer for BLS, said criteria different from those applied by Greenwich were used for evaluating orally administered Therafectin in 218 patients enrolled at 25 sites in the U.S.
Whereas the earlier method of judging trial results called for improvement to baseline in four variables — joint swelling, joint pain, physician evaluation and patient self-evaluation — the newer gauges of therapeutic efficacy, called the Paulus criteria, are more involved.
"In a way, it's arbitrary, as you can see," Lanser said. "The Paulus criteria happen to be the [test] that's been validated by the rheumatoid arthritis community."
The Paulus criteria require that patients show at least a 20 percent response in four of six measures: joint tenderness, joint swelling, physician's and patient's assessments, erythrocyte sedimentation rate and morning stiffness.
By those measures, Therafectin patients showed improvements that were "highly statistically significant" over placebo patients, Lanser said.
BLS decided in late 1995 to replicate one of four earlier studies by Greenwich, called RA-9, using the Paulus criteria, and announced completion of the new study in August 1997. (See BioWorld Today, Nov. 27, 1995, p. 1.)
In September 1997, preliminary analysis of the data showed less promising results, Lanser said, "but when you do the further analysis that we did, there appear to be many indicators of therapeutic efficacy. Obviously, it's a decision the FDA will make."
Among predefined secondary efficacy variables, Therafectin patients also showed statistically significant improvement. After non-steroidal medication was withdrawn, Therafectin patients showed a return to baseline or better, while placebo patients remained worse than baseline to a statistically significant degree.
The beneficial effect was most obvious on joint swelling, Lanser said, and patients with more active disease improved most. Thirty-six percent of Therafectin patients showed at least a 50 percent decrease in the number of swollen joints, compared with 23 percent of placebo patients.
"For RA-9, [Greenwich] had highly statistical significance, but we haven't re-looked at their data using the Paulus criteria," Lanser added.
BLS's stock (NASDAQ:BLSI) closed Tuesday at $2.406, up $0.28. *